PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
32889305-0	2020	Characterization of MET exon 14 alteration and association with clinical outcomes of crizotinib in Chinese lung cancers.	Crizotinib	85-95	SAFB like transcription modulator	Homo sapiens	20-23
32889305-10	2020	A novel MET Y1003C mutation was detected and demonstrated a clinical response to crizotinib.	Crizotinib	81-91	SAFB like transcription modulator	Homo sapiens	8-11
33209633-6	2020	We present a patient with stage IV ALK rearranged lung cancer received who received first line crizotinib at 250 mg twice daily, then at progression, second line alectinib at 600 mg twice daily.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	35-38
32865687-0	2020	Efficacy and Safety of Crizotinib in the Treatment of Advanced Non-Small-Cell Lung Cancer with ROS1 Rearrangement or MET Alteration: A Systematic Review and Meta-Analysis.	Crizotinib	23-33	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	95-99
32865687-0	2020	Efficacy and Safety of Crizotinib in the Treatment of Advanced Non-Small-Cell Lung Cancer with ROS1 Rearrangement or MET Alteration: A Systematic Review and Meta-Analysis.	Crizotinib	23-33	SAFB like transcription modulator	Homo sapiens	117-120
32865687-1	2020	BACKGROUND: Crizotinib has been approved for the treatment of non-small-cell lung cancer (NSCLC) with ROS proto-oncogene 1 (ROS1) gene fusion.	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	124-128
32865687-7	2020	Among patients with ROS1-positive NSCLC, crizotinib exhibited a pooled DCR of 93.2% (95% confidence interval [CI] 90.8-95.5) and a pooled ORR of 77.4% (95% CI 72.8-82.1).	Crizotinib	41-51	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	20-24
32865687-9	2020	For NSCLC with MET alterations, crizotinib was associated with a lower efficacy (DCR 78.9% [95% CI 70.3-87.4] and ORR 40.6% [95% CI 28.3-53.0]).	Crizotinib	32-42	SAFB like transcription modulator	Homo sapiens	15-18
32865687-12	2020	CONCLUSION: Our study highlighted and confirmed the efficacy of crizotinib in patients with NSCLC with ROS1 or MET genetic alterations.	Crizotinib	64-74	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	103-107
32865687-12	2020	CONCLUSION: Our study highlighted and confirmed the efficacy of crizotinib in patients with NSCLC with ROS1 or MET genetic alterations.	Crizotinib	64-74	SAFB like transcription modulator	Homo sapiens	111-114
32865687-13	2020	Crizotinib had remarkable effects on advanced NSCLC with ROS1 fusion, as previously reported.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	57-61
32961319-7	2020	Of the 9 unique ALK mutations conferring resistance to crizotinib, NAVIFY Mutation Profiler provided correct annotation for 9/9 mutations whereas OncoKB and COSMIC indicated crizotinib resistance for 8/9 mutations.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	16-19
33145318-0	2020	Novel AMBRA1-ALK fusion identified by next-generation sequencing in advanced gallbladder cancer responds to crizotinib: a case report.	Crizotinib	108-118	autophagy and beclin 1 regulator 1	Homo sapiens	6-12
32942985-7	2020	A therapy regimen incorporating TKIs Gefitinib and Crizotinib was offered to the EGFR and ALK fusion positive patients, respectively.	Crizotinib	51-61	epidermal growth factor receptor	Homo sapiens	81-85
32942985-7	2020	A therapy regimen incorporating TKIs Gefitinib and Crizotinib was offered to the EGFR and ALK fusion positive patients, respectively.	Crizotinib	51-61	ALK receptor tyrosine kinase	Homo sapiens	90-93
32591465-14	2020	Confirmed ORR was 33.3% among the 6 RECIST-evaluable crizotinib-refractory ROS1+ NSCLC patients.	Crizotinib	53-63	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	75-79
32591465-18	2020	Preliminary efficacy was observed in crizotinib-refractory ROS1+ NSCLC patients.	Crizotinib	37-47	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	59-63
32648452-0	2020	Durable complete response after afatinib and crizotinib in an advanced non-small cell lung cancer patient with EGFR L861Q mutation and acquired MET amplification: a case report.	Crizotinib	45-55	epidermal growth factor receptor	Homo sapiens	111-115
32648452-7	2020	To our knowledge, this is the first time that afatinib induced longterm liver remission in a patient with an EGFR non-classical mutation, and in whom crizotinib with afatinib proved to be a reliable treatment for overcoming MET amplification resistance with an EGFR non-classical mutation.	Crizotinib	150-160	epidermal growth factor receptor	Homo sapiens	261-265
32878782-1	2020	BACKGROUND/AIM: ALK inhibitors like Crizotinib, Ceritinib and Alectinib are targeted therapies used in patients with anaplastic lymphoma kinase (ALK)-positive, advanced non-small cell lung cancer (NSCLC).	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	16-19
32878782-1	2020	BACKGROUND/AIM: ALK inhibitors like Crizotinib, Ceritinib and Alectinib are targeted therapies used in patients with anaplastic lymphoma kinase (ALK)-positive, advanced non-small cell lung cancer (NSCLC).	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	117-143
32878782-1	2020	BACKGROUND/AIM: ALK inhibitors like Crizotinib, Ceritinib and Alectinib are targeted therapies used in patients with anaplastic lymphoma kinase (ALK)-positive, advanced non-small cell lung cancer (NSCLC).	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	145-148
33145318-0	2020	Novel AMBRA1-ALK fusion identified by next-generation sequencing in advanced gallbladder cancer responds to crizotinib: a case report.	Crizotinib	108-118	ALK receptor tyrosine kinase	Homo sapiens	13-16
33145318-3	2020	We report a case of a 58-year-old Chinese woman with GBC who was detected with a novel ALK genomic rearrangement and received crizotinib after progression from first-line chemotherapy.	Crizotinib	126-136	ALK receptor tyrosine kinase	Homo sapiens	87-90
33145318-9	2020	AMBRA1-ALK has not been previously reported in any solid tumors and its sensitivity to crizotinib is not well characterized.	Crizotinib	87-97	autophagy and beclin 1 regulator 1	Homo sapiens	0-6
33145318-9	2020	AMBRA1-ALK has not been previously reported in any solid tumors and its sensitivity to crizotinib is not well characterized.	Crizotinib	87-97	ALK receptor tyrosine kinase	Homo sapiens	7-10
32409267-0	2020	Treatment Patterns and Clinical Outcomes Among Patients With ROS1-rearranged Non-small-cell Lung Cancer Progressing on Crizotinib.	Crizotinib	119-129	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	61-65
32353713-1	2020	Crizotinib is a tyrosine kinase inhibitor that has been found to be effective in the treatment of anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	98-124
32353713-1	2020	Crizotinib is a tyrosine kinase inhibitor that has been found to be effective in the treatment of anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	126-129
32409267-2	2020	Despite the fact that most patients initially respond to the first-generation ROS1 tyrosine kinase inhibitor (TKI) crizotinib, relapse invariably occurs, and therapeutic options upon disease progression are limited.	Crizotinib	115-125	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	78-82
32409267-10	2020	CONCLUSION: In this study, we reported that a subset of patients with ROS1-rearranged NSCLC may benefit from treatment with TKIs beyond progression and that sequential treatment with crizotinib followed by lorlatinib is associated with improved OS in patients with ROS1-rearranged NSCLC.	Crizotinib	183-193	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	70-74
32409267-10	2020	CONCLUSION: In this study, we reported that a subset of patients with ROS1-rearranged NSCLC may benefit from treatment with TKIs beyond progression and that sequential treatment with crizotinib followed by lorlatinib is associated with improved OS in patients with ROS1-rearranged NSCLC.	Crizotinib	183-193	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	265-269
32511029-2	2020	Crizotinib, ceritinib, alectinib, and brigatinib are active ALK inhibitors (ALKi) used to treat this oncogene-driven subset of NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	60-63
32854915-0	2020	Sustained Response to Crizotinib After Resistance to First-Line Alectinib Treatment in Two Patients With ALK-Rearranged NSCLC.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	105-108
32702569-0	2020	Effectiveness and prognostic factors of first-line crizotinib treatment in patients with ROS1-rearranged non-small cell lung cancer: A multicenter retrospective study.	Crizotinib	51-61	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	89-93
32702569-2	2020	The aim of this study was to determine the effectiveness of crizotinib as first-line treatment in patients with ROS1 rearranged NSCLC.	Crizotinib	60-70	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	112-116
32702569-3	2020	METHODS: The data of 56 patients with ROS1-rearranged advanced NSCLC who received first-line crizotinib treatment from 5 hospitals in China were retrospectively reviewed.	Crizotinib	93-103	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	38-42
32702569-10	2020	Four out of 8 patients (50 %) with crizotinib resistance harbored a G2032R mutation in the ROS1 kinase domain.	Crizotinib	35-45	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	91-95
32702569-11	2020	CONCLUSIONS: First-line crizotinib treatment is beneficial in Chinese patients with ROS1-rearranged advanced NSCLC.	Crizotinib	24-34	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	84-88
32702569-12	2020	Resistance to crizotinib correlated with the G2032R mutation in the ROS1 kinase domain.	Crizotinib	14-24	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	68-72
32882995-4	2020	Crizotinib is an ATP-competitive tyrosine kinase inhibitor that targets c-MET, ROS1, and ALK.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	72-77
32882995-4	2020	Crizotinib is an ATP-competitive tyrosine kinase inhibitor that targets c-MET, ROS1, and ALK.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	79-83
32882995-4	2020	Crizotinib is an ATP-competitive tyrosine kinase inhibitor that targets c-MET, ROS1, and ALK.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	89-92
32872120-5	2020	Nevertheless, TP53 co-mutations are relatively frequent and are associated with adverse outcome of crizotinib treatment, whereas utility of next-generation ALK inhibitors in TP53-mutant tumors is still unknown.	Crizotinib	99-109	tumor protein p53	Homo sapiens	14-18
32830600-0	2021	68-months progression-free survival with crizotinib treatment in a patient with metastatic ALK positive lung adenocarcinoma and sarcoidosis: A case report.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	91-94
32830600-9	2021	The patient with positive ALK fusion mutation started crizotinib treatment in July 2014.	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	26-29
32819126-15	2021	Crizotinib with preventive WBRT may be the optimal choice for NSCLC patients harboring ALK mutation in the initial treatment of gastric metastasis.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	87-90
32974126-2	2020	In this multicenter retrospective study, we evaluated the clinical efficacy of crizotinib according to the ALK rearrangement variants and concomitant mutations present.	Crizotinib	79-89	ALK receptor tyrosine kinase	Homo sapiens	107-110
32974126-8	2020	A multivariable analysis indicated that concomitant oncogene mutations and tumor-suppressor gene mutations were both negative factors influencing the efficacy of crizotinib in ALK rearrangement NSCLC.	Crizotinib	162-172	ALK receptor tyrosine kinase	Homo sapiens	176-179
32335105-1	2020	Brigatinib, a multi-target kinase inhibitor, is primarily used to treat anaplastic lymphoma kinase (ALK)-positive patients with advanced non-small cell lung cancer (NSCLC) who have previously received crizotinib or are resistant to crizotinib.	Crizotinib	201-211	ALK receptor tyrosine kinase	Homo sapiens	100-103
32631505-1	2020	N-[18F]fluoroacetylcrizotinib, a fluorine-18 labeled derivative of the first FDA approved tyrosine kinase inhibitor (TKI) for the treatment of Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC), crizotinib, was successfully synthesized for use in positron emission tomography (PET).	Crizotinib	19-29	ALK receptor tyrosine kinase	Homo sapiens	143-169
32631505-1	2020	N-[18F]fluoroacetylcrizotinib, a fluorine-18 labeled derivative of the first FDA approved tyrosine kinase inhibitor (TKI) for the treatment of Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC), crizotinib, was successfully synthesized for use in positron emission tomography (PET).	Crizotinib	19-29	ALK receptor tyrosine kinase	Homo sapiens	171-174
32631505-4	2020	The utility of PET in this context provides a non-invasive, quantifiable method to inform on the pharmacokinetics of an ALK-inhibitor such as crizotinib prior to a clinical trial, as well as during a trial in the event of acquired drug resistance.	Crizotinib	142-152	ALK receptor tyrosine kinase	Homo sapiens	120-123
32484926-7	2020	Signaling pathways required for crizotinib-induced apoptosis of autophagic cells were explored with flow cytometric analysis, Western blot analysis, short-hairpin RNA knockdown of autophagic proteins, and small-molecule inhibitors of STAT3 and BCL-2.	Crizotinib	32-42	signal transducer and activator of transcription 3	Homo sapiens	234-239
32673828-0	2020	Crizotinib inhibits activation of MET pathway caused by MET extracellular SEMA domain duplication.	Crizotinib	0-10	semaphorin 3B	Homo sapiens	74-78
32673828-10	2020	CONCLUSION: Crizotinib treatment resulted in a clinical response in a patient with MET SEMA duplication.	Crizotinib	12-22	semaphorin 3B	Homo sapiens	87-91
32631560-0	2020	Synthesis and evaluation of 18F labeled crizotinib derivative [18F]FPC as a novel PET probe for imaging c-MET-positive NSCLC tumor.	Crizotinib	40-50	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	104-109
32484926-7	2020	Signaling pathways required for crizotinib-induced apoptosis of autophagic cells were explored with flow cytometric analysis, Western blot analysis, short-hairpin RNA knockdown of autophagic proteins, and small-molecule inhibitors of STAT3 and BCL-2.	Crizotinib	32-42	BCL2 apoptosis regulator	Homo sapiens	244-249
32484926-8	2020	RESULTS: Induction of autophagy by reexpression of DIRAS3 or serum starvation in multiple OvCa cell lines significantly reduced the 50% inhibitory concentration of crizotinib and other ALK inhibitors.	Crizotinib	164-174	DIRAS family GTPase 3	Homo sapiens	51-57
32484926-9	2020	In 2 human OvCa xenograft models, the DIRAS3-expressing tumors treated with crizotinib had significantly decreased tumor burden and long-term survival in 67% to 79% of mice.	Crizotinib	76-86	DIRAS family GTPase 3	Homo sapiens	38-44
32484926-10	2020	Crizotinib treatment of autophagic cancer cells further enhanced autophagy and induced autophagy-mediated apoptosis by decreasing phosphorylated STAT3 and BCL-2 signaling.	Crizotinib	0-10	signal transducer and activator of transcription 3	Homo sapiens	145-150
32484926-10	2020	Crizotinib treatment of autophagic cancer cells further enhanced autophagy and induced autophagy-mediated apoptosis by decreasing phosphorylated STAT3 and BCL-2 signaling.	Crizotinib	0-10	BCL2 apoptosis regulator	Homo sapiens	155-160
32347754-1	2020	Aims: To describe the real-world economic burden of patients with anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) treated with post-crizotinib, second-line ALK inhibitor therapy.Materials and methods: Retrospective analysis using data from US Optum: Clinformatics Data Mart administrative claims database.	Crizotinib	162-172	ALK receptor tyrosine kinase	Homo sapiens	66-92
32347754-1	2020	Aims: To describe the real-world economic burden of patients with anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) treated with post-crizotinib, second-line ALK inhibitor therapy.Materials and methods: Retrospective analysis using data from US Optum: Clinformatics Data Mart administrative claims database.	Crizotinib	162-172	ALK receptor tyrosine kinase	Homo sapiens	103-106
32527613-0	2020	Lung adenocarcinoma with a novel SRBD1-ALK Fusion responding to crizotinib.	Crizotinib	64-74	S1 RNA binding domain 1	Homo sapiens	33-38
32648475-0	2020	Matching-adjusted indirect comparison: entrectinib versus crizotinib in ROS1 fusion-positive non-small cell lung cancer.	Crizotinib	58-68	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	72-76
32527613-11	2020	CONCLUSION: To our knowledge, our case is the first case of SRBD1-ALK fusion with excellent response to crizotinib.	Crizotinib	104-114	ALK receptor tyrosine kinase	Homo sapiens	66-69
32527613-12	2020	This case merits further follow-up and provides valuable information on the response to crizotinib of NSCLC patients with SRBD1-ALK fusion.	Crizotinib	88-98	S1 RNA binding domain 1	Homo sapiens	122-127
32527613-12	2020	This case merits further follow-up and provides valuable information on the response to crizotinib of NSCLC patients with SRBD1-ALK fusion.	Crizotinib	88-98	ALK receptor tyrosine kinase	Homo sapiens	128-131
32540202-0	2020	Novel PNPT1-ALK fusion variant exerted significant benefit to crizotinib in NSCLC.	Crizotinib	62-72	polyribonucleotide nucleotidyltransferase 1	Homo sapiens	6-11
32540202-0	2020	Novel PNPT1-ALK fusion variant exerted significant benefit to crizotinib in NSCLC.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	12-15
32540560-0	2020	The clinical efficacy of combinatorial therapy of EGFR-TKI and crizotinib in overcoming MET amplification-mediated resistance from prior EGFR-TKI therapy.	Crizotinib	63-73	epidermal growth factor receptor	Homo sapiens	137-141
32540560-2	2020	Combinatorial therapy of EGFR-TKI and crizotinib has been explored as a strategy to overcome resistance by simultaneously targeting both EGFR and MET pathways; however, no consensus still exists on the optimal combination regimen with the most benefit.	Crizotinib	38-48	epidermal growth factor receptor	Homo sapiens	137-141
32540560-8	2020	Moreover, analysis of acquired resistance mechanisms from nine patients identified EGFR T790 M from three patients who progressed from first-generation EGFR-TKI and crizotinib, while EGFR T790 M/trans-C797S and L718Q, EGFR G724S, and CCDC6-RET fusion were detected from one patient each who progressed from osimertinib and crizotinib regimen.	Crizotinib	165-175	epidermal growth factor receptor	Homo sapiens	83-87
32540560-8	2020	Moreover, analysis of acquired resistance mechanisms from nine patients identified EGFR T790 M from three patients who progressed from first-generation EGFR-TKI and crizotinib, while EGFR T790 M/trans-C797S and L718Q, EGFR G724S, and CCDC6-RET fusion were detected from one patient each who progressed from osimertinib and crizotinib regimen.	Crizotinib	323-333	epidermal growth factor receptor	Homo sapiens	83-87
32540560-10	2020	CONCLUSIONS: Our study provides clinical evidence of the efficacy of combinatorial regimen with either first- or third-generation EGFR-TKI and crizotinib after the emergence of MET amplification-mediated EGFR-TKI resistance in patients with EGFR-mutant NSCLC.	Crizotinib	143-153	epidermal growth factor receptor	Homo sapiens	204-208
32540560-10	2020	CONCLUSIONS: Our study provides clinical evidence of the efficacy of combinatorial regimen with either first- or third-generation EGFR-TKI and crizotinib after the emergence of MET amplification-mediated EGFR-TKI resistance in patients with EGFR-mutant NSCLC.	Crizotinib	143-153	epidermal growth factor receptor	Homo sapiens	204-208
32563740-0	2020	Investigation on the prognostic impact of concurrent genomic alterations in crizotinib-treated EML4-ALK-rearranged advanced non-small cell lung cancer patients.	Crizotinib	76-86	EMAP like 4	Homo sapiens	95-99
32563740-0	2020	Investigation on the prognostic impact of concurrent genomic alterations in crizotinib-treated EML4-ALK-rearranged advanced non-small cell lung cancer patients.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	100-103
32487736-9	2020	Interestingly, irinotecan selectively inhibited hOCT1 whereas crizotinib potently inhibited hOCT3-mediated mIBG uptake.	Crizotinib	62-72	solute carrier family 22 member 3	Homo sapiens	92-97
32386255-0	2020	Association of Programmed Death-Ligand 1 Expression with Fusion Variants and Clinical Outcomes in Patients with Anaplastic Lymphoma Kinase-Positive Lung Adenocarcinoma Receiving Crizotinib.	Crizotinib	178-188	CD274 molecule	Homo sapiens	15-40
32386255-3	2020	We aimed to evaluate the impact of PD-L1 in patients with ALK-positive lung ADC receiving crizotinib.	Crizotinib	90-100	CD274 molecule	Homo sapiens	35-40
32386255-3	2020	We aimed to evaluate the impact of PD-L1 in patients with ALK-positive lung ADC receiving crizotinib.	Crizotinib	90-100	ALK receptor tyrosine kinase	Homo sapiens	58-61
32386255-9	2020	The crizotinib objective response rate (ORR) and progression-free survival (PFS) was better in tumors with negative PD-L1 expression (ORR/PFS in PD-L1 0% vs. 1%-49% vs. 50%-100%: 60.7%/11.8 months vs. 38.5%/6.5 months vs. 36.4%/4.0 months, p = .007/.022).	Crizotinib	4-14	CD274 molecule	Homo sapiens	116-121
32386255-9	2020	The crizotinib objective response rate (ORR) and progression-free survival (PFS) was better in tumors with negative PD-L1 expression (ORR/PFS in PD-L1 0% vs. 1%-49% vs. 50%-100%: 60.7%/11.8 months vs. 38.5%/6.5 months vs. 36.4%/4.0 months, p = .007/.022).	Crizotinib	4-14	CD274 molecule	Homo sapiens	145-150
32386255-12	2020	CONCLUSION: Positive PD-L1 expression was associated with unfavorable clinical outcomes in patients with ALK-positive lung ADC receiving crizotinib.	Crizotinib	137-147	CD274 molecule	Homo sapiens	21-26
32386255-12	2020	CONCLUSION: Positive PD-L1 expression was associated with unfavorable clinical outcomes in patients with ALK-positive lung ADC receiving crizotinib.	Crizotinib	137-147	ALK receptor tyrosine kinase	Homo sapiens	105-108
32386255-14	2020	Similar to the negative impact of programmed death-ligand 1 (PD-L1) in epidermal growth factor receptor mutant tumors treated with TKIs, this study demonstrated that positive PD-L1 expression was also associated with worse response rate and shorter progression-free survival of anaplastic lymphoma kinase (ALK)-positive adenocarcinoma treated with crizotinib.	Crizotinib	348-358	CD274 molecule	Homo sapiens	175-180
32386255-16	2020	Testing PD-L1 before initiating crizotinib for ALK-positive lung cancer could be a simple method to provide important prognostic information.	Crizotinib	32-42	ALK receptor tyrosine kinase	Homo sapiens	47-50
32821654-2	2020	Crizotinib is a specific anaplastic lymphoma kinase (ALK) inhibitor, which was initially developed in non-small cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	25-51
32821654-2	2020	Crizotinib is a specific anaplastic lymphoma kinase (ALK) inhibitor, which was initially developed in non-small cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	53-56
32821654-10	2020	A tumor board discussion based on molecular characteristics of the tumor suggested initiating a daily treatment by crizotinib, a specific ALK inhibitor.	Crizotinib	115-125	ALK receptor tyrosine kinase	Homo sapiens	138-141
32821654-12	2020	CONCLUSION: This case highlights an unexpected efficacy of crizotinib in an ALK-rearranged thyroid tumor, and the need of further assessments.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	76-79
32801744-1	2020	Introduction: Reliable diagnostic approaches to detect ALK rearrangement are critical for selecting patients eligible for crizotinib therapy.	Crizotinib	122-132	ALK receptor tyrosine kinase	Homo sapiens	55-58
32801744-6	2020	Of the 76 crizotinib-treated patients whose ALK status was assessed by both NGS and IHC, 78.9% of the patients had concordant ALK status (NGS-positive/IHC-positive), 18.4% patients were NGS-positive but IHC-negative, and 2 patients were IHC-positive but NGS-negative.	Crizotinib	10-20	ALK receptor tyrosine kinase	Homo sapiens	44-47
32801744-6	2020	Of the 76 crizotinib-treated patients whose ALK status was assessed by both NGS and IHC, 78.9% of the patients had concordant ALK status (NGS-positive/IHC-positive), 18.4% patients were NGS-positive but IHC-negative, and 2 patients were IHC-positive but NGS-negative.	Crizotinib	10-20	ALK receptor tyrosine kinase	Homo sapiens	126-129
32792859-0	2020	Chidamide increases the sensitivity of Non-small Cell Lung Cancer to Crizotinib by decreasing c-MET mRNA methylation.	Crizotinib	69-79	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	94-99
32792859-1	2020	Introduction: Crizotinib is a kinase inhibitor targeting c-MET/ALK/ROS1 used as the first-line chemical for the treatment of non-small cell lung cancer (NSCLC) with ALK mutations.	Crizotinib	14-24	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	57-62
32792859-1	2020	Introduction: Crizotinib is a kinase inhibitor targeting c-MET/ALK/ROS1 used as the first-line chemical for the treatment of non-small cell lung cancer (NSCLC) with ALK mutations.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	63-66
32792859-1	2020	Introduction: Crizotinib is a kinase inhibitor targeting c-MET/ALK/ROS1 used as the first-line chemical for the treatment of non-small cell lung cancer (NSCLC) with ALK mutations.	Crizotinib	14-24	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	67-71
32792859-1	2020	Introduction: Crizotinib is a kinase inhibitor targeting c-MET/ALK/ROS1 used as the first-line chemical for the treatment of non-small cell lung cancer (NSCLC) with ALK mutations.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	165-168
32792859-5	2020	Results: We found for the first time that chidamide could sensitize the effect of crizotinib in a set of ALK mutation-free NSCLC cell lines, especially those with high levels of c-MET expression.	Crizotinib	82-92	ALK receptor tyrosine kinase	Homo sapiens	105-108
32792859-9	2020	While cells with low or no c-MET expression were primarily resistant to chidamide-crizotinib cotreatment, enforced c-MET overexpression could increase the sensitivity of these cells to chidamide-crizotinib cotreatment.	Crizotinib	195-205	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	115-120
32792859-11	2020	Chidamide-crizotinib cotreatment significantly suppressed the activity of c-MET downstream molecules.	Crizotinib	10-20	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	74-79
32558295-3	2020	Exploring these mechanisms of resistance, we found that EML4-ALK cells parental or resistant to crizotinib, ceritinib or alectinib are remarkably sensitive to inhibition of CDK7/12 with THZ1 and CDK9 with alvocidib or dinaciclib.	Crizotinib	96-106	EMAP like 4	Homo sapiens	56-60
32558295-3	2020	Exploring these mechanisms of resistance, we found that EML4-ALK cells parental or resistant to crizotinib, ceritinib or alectinib are remarkably sensitive to inhibition of CDK7/12 with THZ1 and CDK9 with alvocidib or dinaciclib.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	61-64
32558295-3	2020	Exploring these mechanisms of resistance, we found that EML4-ALK cells parental or resistant to crizotinib, ceritinib or alectinib are remarkably sensitive to inhibition of CDK7/12 with THZ1 and CDK9 with alvocidib or dinaciclib.	Crizotinib	96-106	cyclin dependent kinase 7	Homo sapiens	173-180
32558295-3	2020	Exploring these mechanisms of resistance, we found that EML4-ALK cells parental or resistant to crizotinib, ceritinib or alectinib are remarkably sensitive to inhibition of CDK7/12 with THZ1 and CDK9 with alvocidib or dinaciclib.	Crizotinib	96-106	cyclin dependent kinase 9	Homo sapiens	195-199
32527124-4	2020	Crizotinib was the first ALK inhibitor developed, and it has demonstrated systemic efficacy and strongly improved outcomes in NSCLC patients with ALK-positive when compared with chemotherapy.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	25-28
32527124-4	2020	Crizotinib was the first ALK inhibitor developed, and it has demonstrated systemic efficacy and strongly improved outcomes in NSCLC patients with ALK-positive when compared with chemotherapy.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	146-149
32527124-5	2020	Alectinib was designed specifically to be a more potent and selective anti-ALK therapeutic agent that could bypass crizotinib resistance.	Crizotinib	115-125	ALK receptor tyrosine kinase	Homo sapiens	75-78
32269053-1	2020	PURPOSE: Although first-line crizotinib treatment leads to clinical benefit in ROS1+ lung cancer, high prevalence of crizotinib-resistant ROS1-G2032R (ROS1G2032R) mutation and progression in the central nervous system (CNS) represents a therapeutic challenge.	Crizotinib	29-39	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	79-83
32269053-1	2020	PURPOSE: Although first-line crizotinib treatment leads to clinical benefit in ROS1+ lung cancer, high prevalence of crizotinib-resistant ROS1-G2032R (ROS1G2032R) mutation and progression in the central nervous system (CNS) represents a therapeutic challenge.	Crizotinib	117-127	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	138-142
32651063-0	2021	Next-Generation Sequencing Identified a Novel Crizotinib-Sensitive PLB1-ALK Rearrangement in Lung Large-Cell Neuroendocrine Carcinoma.	Crizotinib	46-56	phospholipase B1	Homo sapiens	67-71
32651063-0	2021	Next-Generation Sequencing Identified a Novel Crizotinib-Sensitive PLB1-ALK Rearrangement in Lung Large-Cell Neuroendocrine Carcinoma.	Crizotinib	46-56	ALK receptor tyrosine kinase	Homo sapiens	72-75
32647695-0	2020	Perioperative crizotinib in a patient with stage IIIB ALK-positive non-small cell lung cancer: a case report.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	54-57
32229347-2	2020	In order to overcome this drawback, the first hypoxia-activatable 2-nitroimidazole-based prodrugs of the clinically approved ALK and c-MET inhibitor crizotinib were developed.	Crizotinib	149-159	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	133-138
32112982-0	2020	Detection of non-reciprocal/reciprocal ALK translocation as poor predictive marker in first-line crizotinib-treated ALK-rearranged non-small cell lung cancer patients.	Crizotinib	97-107	ALK receptor tyrosine kinase	Homo sapiens	39-42
32112982-0	2020	Detection of non-reciprocal/reciprocal ALK translocation as poor predictive marker in first-line crizotinib-treated ALK-rearranged non-small cell lung cancer patients.	Crizotinib	97-107	ALK receptor tyrosine kinase	Homo sapiens	116-119
32112982-2	2020	Our study aimed to assess the impact of harboring 5"-ALK on the efficacy of crizotinib.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	53-56
32112982-4	2020	The efficacy of crizotinib as first-line therapy was evaluated in 112 patients according to the retention of 5"-ALK.	Crizotinib	16-26	ALK receptor tyrosine kinase	Homo sapiens	112-115
32217130-0	2020	IMAGE OF THE MONTH: A Novel Linc00308/D21S2088E Intergenic Region-ALK Fusion and Its Enduring Clinical Responses to Crizotinib.	Crizotinib	116-126	ALK receptor tyrosine kinase	Homo sapiens	66-69
32776005-3	2020	Both crizotinib and entrectinib, multitargeted tyrosine kinase inhibitors (TKIs) have now received approval by the FDA for treatment of patients with advanced ROS1-rearranged lung cancers; however, the clinical efficacy and safety of these drugs have been derived from expansion cohorts of single-arm phase I or basket clinical trials with relatively small populations of this clinically and molecularly distinct subgroup.	Crizotinib	5-15	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	159-163
32776005-6	2020	We describe cases of advanced ROS1-rearranged lung cancer receiving crizotinib, entrectinib, and/or lorlatinib in first and later line treatment settings to dissect the current state of evidence supporting management decisions for these patients.	Crizotinib	68-78	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	30-34
33354548-8	2020	Patients with ERBB2/3 amplification received trastuzumab with capecitabine or nab-paclitaxel, and patients with MET amplification were treated with crizotinib.	Crizotinib	148-158	SAFB like transcription modulator	Homo sapiens	112-115
33354548-15	2020	One patient with MET amplification responded to crizotinib for 4 weeks.	Crizotinib	48-58	SAFB like transcription modulator	Homo sapiens	17-20
32563740-1	2020	BACKGROUND: Despite the efficacy of crizotinib in non-small cell lung cancer (NSCLC) with genomic rearrangement between echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK), clinical outcomes are heterogeneous among these patients.	Crizotinib	36-46	EMAP like 4	Homo sapiens	120-168
32563740-1	2020	BACKGROUND: Despite the efficacy of crizotinib in non-small cell lung cancer (NSCLC) with genomic rearrangement between echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK), clinical outcomes are heterogeneous among these patients.	Crizotinib	36-46	EMAP like 4	Homo sapiens	170-174
32563740-1	2020	BACKGROUND: Despite the efficacy of crizotinib in non-small cell lung cancer (NSCLC) with genomic rearrangement between echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK), clinical outcomes are heterogeneous among these patients.	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	180-206
32563740-3	2020	METHODS: We retrospectively analyzed the clinical and targeted sequencing data from 32 crizotinib-treated patients with EML4-ALK-rearranged advanced NSCLC.	Crizotinib	87-97	EMAP like 4	Homo sapiens	120-124
32563740-3	2020	METHODS: We retrospectively analyzed the clinical and targeted sequencing data from 32 crizotinib-treated patients with EML4-ALK-rearranged advanced NSCLC.	Crizotinib	87-97	ALK receptor tyrosine kinase	Homo sapiens	125-128
32563740-11	2020	CONCLUSION: Our study revealed that concurrent deleterious mutations, particularly copy number amplifications in oncogenic genes have prognostic implications in patients with EML4-ALK-rearranged NSCLC receiving crizotinib therapy.	Crizotinib	211-221	EMAP like 4	Homo sapiens	175-179
32563740-11	2020	CONCLUSION: Our study revealed that concurrent deleterious mutations, particularly copy number amplifications in oncogenic genes have prognostic implications in patients with EML4-ALK-rearranged NSCLC receiving crizotinib therapy.	Crizotinib	211-221	ALK receptor tyrosine kinase	Homo sapiens	180-183
32953517-8	2020	Patients with ALK variant 1 who had baseline BM had significantly shorter TTF than non-variant 1 with baseline BM when treated with first-line crizotinib (median TTF: 9.1 vs. 14.9 months, HR =2.68, P=0.037).	Crizotinib	143-153	ALK receptor tyrosine kinase	Homo sapiens	14-17
32953517-11	2020	Conclusions: Patients with ALK variant 1 and baseline BM had inferior TTF on first-line crizotinib treatment and presented with more aggressive radiological features.	Crizotinib	88-98	ALK receptor tyrosine kinase	Homo sapiens	27-30
32923895-0	2020	CNS Metastases in Patients With MET Exon 14-Altered Lung Cancers and Outcomes With Crizotinib.	Crizotinib	83-93	SAFB like transcription modulator	Homo sapiens	32-35
32923895-4	2020	The incidence of brain metastases and the outcomes of MET inhibition with crizotinib were analyzed.	Crizotinib	74-84	SAFB like transcription modulator	Homo sapiens	54-57
32724815-14	2020	IL10 downregulated the expression level of PD-L1 and enhanced the efficacy of crizotinib via the Met signaling pathway in the LIHC cells.	Crizotinib	78-88	interleukin 10	Homo sapiens	0-4
32695536-10	2020	She was treated with ALK inhibitor Crizotinib.	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	21-24
32632141-10	2020	Treatment with crizotinib, a c-MET inhibitor, decreased cellular viability of BRN2-expressing cells under non-adherent conditions to death by anoikis.	Crizotinib	15-25	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	29-34
32632141-10	2020	Treatment with crizotinib, a c-MET inhibitor, decreased cellular viability of BRN2-expressing cells under non-adherent conditions to death by anoikis.	Crizotinib	15-25	POU class 3 homeobox 2	Rattus norvegicus	78-82
32472430-2	2020	With the approvals of crizotinib in 2012 and ceritinib in 2017, Japan became the first country with multiple ALK TKIs available for first-line or later use in patients with ALK-positive advanced NSCLC.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	109-112
32472430-12	2020	CONCLUSION: At the time of this analysis, most patients who received more than one ALK TKI received crizotinib as the initial ALK TKI.	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	83-86
32284325-2	2020	We have previously demonstrated that combination of the ALK inhibitor crizotinib with the MEK inhibitor selumetinib was highly effective at reducing cell viability of ALK-positive non-small-cell lung cancer (H3122) cells.	Crizotinib	70-80	ALK receptor tyrosine kinase	Homo sapiens	56-59
32284325-2	2020	We have previously demonstrated that combination of the ALK inhibitor crizotinib with the MEK inhibitor selumetinib was highly effective at reducing cell viability of ALK-positive non-small-cell lung cancer (H3122) cells.	Crizotinib	70-80	ALK receptor tyrosine kinase	Homo sapiens	167-170
32284325-3	2020	In this study, we further investigated the efficacy of crizotinib and selumetinib combination therapy in an in vivo xenograft model of ALK-positive lung cancer.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	135-138
32433811-0	2020	A case of ROS1-rearranged lung adenocarcinoma exhibiting pleural effusion caused by crizotinib.	Crizotinib	84-94	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	10-14
32433811-8	2020	In conclusion, crizotinib was considered to cause pleural effusion as an adverse event in a case of ROS1-rearranged lung adenocarcinoma with a complete response.	Crizotinib	15-25	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	100-104
32590748-0	2020	A novel TJP1-ROS1 fusion in malignant peripheral nerve sheath tumor responding to crizotinib: A case report.	Crizotinib	82-92	tight junction protein 1	Homo sapiens	8-12
32590748-0	2020	A novel TJP1-ROS1 fusion in malignant peripheral nerve sheath tumor responding to crizotinib: A case report.	Crizotinib	82-92	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	13-17
32612920-4	2020	We herein report a case of ALK-rearranged lung adenocarcinoma accompanied by SIADH, successfully treated with crizotinib.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	27-30
32654927-0	2021	A Case of HLA-DRB1-MET Rearranged Lung Adenocarcinoma With Rapid Response to Crizotinib.	Crizotinib	77-87	major histocompatibility complex, class II, DR beta 1	Homo sapiens	10-18
32577365-5	2020	The tumor was diagnosed as ROS1-rearranged lung adenocarcinoma, for which crizotinib was administered, which led to improvement of both the primary and metastatic lesions.	Crizotinib	74-84	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	27-31
32383735-2	2020	To address this question, we used a novel "apical efflux ratio" (AP-ER) model to assess P-gp interaction with entrectinib, crizotinib, and larotrectinib, and compared their brain-penetration properties.	Crizotinib	123-133	ATP-binding cassette, subfamily B (MDR/TAP), member 1B	Rattus norvegicus	88-92
32383735-14	2020	Crizotinib and larotrectinib are strong P-gp substrates with poor brain distribution.3.	Crizotinib	0-10	ATP-binding cassette, subfamily B (MDR/TAP), member 1B	Rattus norvegicus	40-44
33479588-1	2021	Ceritinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor with clinical activity in crizotinib-resistant ALK-positive non-small cell lung cancer and in treatment-naive ALK-positive disease.	Crizotinib	102-112	ALK receptor tyrosine kinase	Homo sapiens	61-64
31509456-2	2020	:: The ability to determine ROS1 status has become mandatory for patients with lung adenocarcinoma, as many global authorities have approved crizotinib for patients with ROS1-positive lung adenocarcinoma.	Crizotinib	141-151	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	28-32
31509456-2	2020	:: The ability to determine ROS1 status has become mandatory for patients with lung adenocarcinoma, as many global authorities have approved crizotinib for patients with ROS1-positive lung adenocarcinoma.	Crizotinib	141-151	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	170-174
31177400-0	2020	Activation of IGF-1R pathway and NPM-ALK G1269A mutation confer resistance to crizotinib treatment in NPM-ALK positive lymphoma.	Crizotinib	78-88	insulin like growth factor 1 receptor	Homo sapiens	14-20
31177400-0	2020	Activation of IGF-1R pathway and NPM-ALK G1269A mutation confer resistance to crizotinib treatment in NPM-ALK positive lymphoma.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	37-40
31177400-0	2020	Activation of IGF-1R pathway and NPM-ALK G1269A mutation confer resistance to crizotinib treatment in NPM-ALK positive lymphoma.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	106-109
31177400-1	2020	ALK-positive anaplastic large cell lymphoma (ALCL) represents a subset of non-Hodgkin"s lymphoma that is treated with crizotinib, a dual ALK/MET inhibitor.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	0-3
31177400-1	2020	ALK-positive anaplastic large cell lymphoma (ALCL) represents a subset of non-Hodgkin"s lymphoma that is treated with crizotinib, a dual ALK/MET inhibitor.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	137-140
31177400-7	2020	In the crizotinib-resistant ALCL cell model, the IGF-1R pathway was activated, and combined ALK/IGF-1R inhibition improved therapeutic efficacy.	Crizotinib	7-17	insulin like growth factor 1 receptor	Homo sapiens	49-55
31177400-7	2020	In the crizotinib-resistant ALCL cell model, the IGF-1R pathway was activated, and combined ALK/IGF-1R inhibition improved therapeutic efficacy.	Crizotinib	7-17	ALK receptor tyrosine kinase	Homo sapiens	92-95
31177400-7	2020	In the crizotinib-resistant ALCL cell model, the IGF-1R pathway was activated, and combined ALK/IGF-1R inhibition improved therapeutic efficacy.	Crizotinib	7-17	insulin like growth factor 1 receptor	Homo sapiens	96-102
31177400-8	2020	Furthermore, we also detected the NPM-ALK G1269A mutation, which had previously been demonstrated to result in decreased affinity for crizotinib, in the resistant cell model.	Crizotinib	134-144	ALK receptor tyrosine kinase	Homo sapiens	38-41
31177400-10	2020	Thus, we have shown that second-generation ALK tyrosine kinase inhibitors or IGF-1R inhibitors are effective in treating crizotinib-resistant tumors.	Crizotinib	121-131	ALK receptor tyrosine kinase	Homo sapiens	43-46
31177400-10	2020	Thus, we have shown that second-generation ALK tyrosine kinase inhibitors or IGF-1R inhibitors are effective in treating crizotinib-resistant tumors.	Crizotinib	121-131	insulin like growth factor 1 receptor	Homo sapiens	77-83
32112982-9	2020	Crizotinib-treated patients with non-reciprocal/reciprocal ALK translocation had significantly shorter mPFS compared with patients carrying 3"-ALK fusion alone (6.1m vs. 12.0m, p=0.001) or with EML4-ALK fusion alone (6.1m vs. 12.6m, p=0.001).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	59-62
32112982-9	2020	Crizotinib-treated patients with non-reciprocal/reciprocal ALK translocation had significantly shorter mPFS compared with patients carrying 3"-ALK fusion alone (6.1m vs. 12.0m, p=0.001) or with EML4-ALK fusion alone (6.1m vs. 12.6m, p=0.001).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	143-146
32112982-9	2020	Crizotinib-treated patients with non-reciprocal/reciprocal ALK translocation had significantly shorter mPFS compared with patients carrying 3"-ALK fusion alone (6.1m vs. 12.0m, p=0.001) or with EML4-ALK fusion alone (6.1m vs. 12.6m, p=0.001).	Crizotinib	0-10	EMAP like 4	Homo sapiens	194-198
32112982-9	2020	Crizotinib-treated patients with non-reciprocal/reciprocal ALK translocation had significantly shorter mPFS compared with patients carrying 3"-ALK fusion alone (6.1m vs. 12.0m, p=0.001) or with EML4-ALK fusion alone (6.1m vs. 12.6m, p=0.001).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	143-146
32112982-10	2020	Multivariate analysis revealed that harboring non-reciprocal/reciprocal ALK translocation was an independent predictor of worse PFS for crizotinib-treated ALK-rearranged NSCLC (p=0.0046).	Crizotinib	136-146	ALK receptor tyrosine kinase	Homo sapiens	72-75
32112982-10	2020	Multivariate analysis revealed that harboring non-reciprocal/reciprocal ALK translocation was an independent predictor of worse PFS for crizotinib-treated ALK-rearranged NSCLC (p=0.0046).	Crizotinib	136-146	ALK receptor tyrosine kinase	Homo sapiens	155-158
32112982-11	2020	CONCLUSIONS: Presence of non-reciprocal/reciprocal ALK translocation was predictive for worse PFS and greater likelihood of baseline brain metastases in patients with ALK-rearranged NSCLC who received first-line crizotinib.	Crizotinib	212-222	ALK receptor tyrosine kinase	Homo sapiens	51-54
32112982-11	2020	CONCLUSIONS: Presence of non-reciprocal/reciprocal ALK translocation was predictive for worse PFS and greater likelihood of baseline brain metastases in patients with ALK-rearranged NSCLC who received first-line crizotinib.	Crizotinib	212-222	ALK receptor tyrosine kinase	Homo sapiens	167-170
32212216-7	2020	KEY POINTS: A lung adenocarcinoma patient harboring concurrent NLRC4-ALK and EML4-ALK fusion mutations benefited from crizotinib after surgery.	Crizotinib	118-128	NLR family CARD domain containing 4	Homo sapiens	63-68
32212216-7	2020	KEY POINTS: A lung adenocarcinoma patient harboring concurrent NLRC4-ALK and EML4-ALK fusion mutations benefited from crizotinib after surgery.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	69-72
32212216-7	2020	KEY POINTS: A lung adenocarcinoma patient harboring concurrent NLRC4-ALK and EML4-ALK fusion mutations benefited from crizotinib after surgery.	Crizotinib	118-128	EMAP like 4	Homo sapiens	77-81
32212216-7	2020	KEY POINTS: A lung adenocarcinoma patient harboring concurrent NLRC4-ALK and EML4-ALK fusion mutations benefited from crizotinib after surgery.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	82-85
32527613-0	2020	Lung adenocarcinoma with a novel SRBD1-ALK Fusion responding to crizotinib.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	39-42
32527613-3	2020	Majority of the ALK actionable rearrangements were sensitive to crizotinib, yet some rare fusion types may less benefit than EML4-ALK.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	16-19
32527613-5	2020	To our knowledge, this case is the first report showed clinical evidence of SRBD1-ALK fusion responding to crizotinib.	Crizotinib	107-117	S1 RNA binding domain 1	Homo sapiens	76-81
32527613-5	2020	To our knowledge, this case is the first report showed clinical evidence of SRBD1-ALK fusion responding to crizotinib.	Crizotinib	107-117	ALK receptor tyrosine kinase	Homo sapiens	82-85
32527613-11	2020	CONCLUSION: To our knowledge, our case is the first case of SRBD1-ALK fusion with excellent response to crizotinib.	Crizotinib	104-114	S1 RNA binding domain 1	Homo sapiens	60-65
32547089-4	2020	After the first-line chemotherapy failed, the patient received crizotinib due to the presence of EML4-ALK fusion by next-generation sequencing (NGS).	Crizotinib	63-73	EMAP like 4	Homo sapiens	97-101
32547089-4	2020	After the first-line chemotherapy failed, the patient received crizotinib due to the presence of EML4-ALK fusion by next-generation sequencing (NGS).	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	102-105
32528877-0	2020	Low-Dose Crizotinib, a Tyrosine Kinase Inhibitor, Highly and Specifically Sensitizes P-Glycoprotein-Overexpressing Chemoresistant Cancer Cells Through Induction of Late Apoptosis in vivo and in vitro.	Crizotinib	9-19	ATP binding cassette subfamily B member 1	Homo sapiens	85-99
32283024-6	2020	Crizotinib prefers to bind the wild-type ALK kinase domain, whereas Ceritinib binds more favorably to the mutated ALK kinase domain, in agreement with experimental results.	Crizotinib	0-10	Anaplastic lymphoma kinase	Drosophila melanogaster	41-44
32528877-6	2020	In a detailed quantitative analysis using both lower doses and time-duration treatments, we demonstrated that crizotinib, which increased the levels of apoptosis and G2 arrest, was the best TKI to induce sensitization in P-gp-overexpressing KBV20C cells.	Crizotinib	110-120	ATP binding cassette subfamily B member 1	Homo sapiens	221-225
32528877-9	2020	In mice bearing xenografted P-gp-overexpressing KBV20C cells, we confirmed that crizotinib significantly reduced tumor growth and weight, without apparent side effects.	Crizotinib	80-90	phosphoglycolate phosphatase	Mus musculus	28-32
32528877-10	2020	In addition, although lapatinib and crizotinib have a high P-gp inhibitory activity, we found that co-treatment with crizotinib and vincristine (VIC) did not have much of a sensitization effect on KBV20C cells, whereas lapatinib had a high sensitization effect on VIC-treated KBV20C cells.	Crizotinib	36-46	phosphoglycolate phosphatase	Mus musculus	59-63
32528877-12	2020	These findings provide valuable information regarding the sensitization of drug-resistant cells and indicate that low-dose crizotinib monotherapy may be used in patients with specific P-gp-overexpressing chemoresistant cancer.	Crizotinib	123-133	ATP binding cassette subfamily B member 1	Homo sapiens	184-188
32122695-0	2020	A case treated with Crizotinib after secondary MET amplification of A double Rare L747S and G719S EGFR mutation Pulmonary Sarcomatoid Carcinoma.	Crizotinib	20-30	epidermal growth factor receptor	Homo sapiens	98-102
32923114-5	2020	Crizotinib-resistant cell line was generated for measuring the association between Crizotinib resistance and PD-L1 expression.	Crizotinib	0-10	CD274 antigen	Mus musculus	109-114
32923114-5	2020	Crizotinib-resistant cell line was generated for measuring the association between Crizotinib resistance and PD-L1 expression.	Crizotinib	83-93	CD274 antigen	Mus musculus	109-114
32923114-7	2020	PD-L1 expression was significantly up-regulated in bronchial epithelial cells after forced expression of ROS1 fusion and was eliminated when HCC78 xenograft mouse models were treated with Crizotinib.	Crizotinib	188-198	CD274 antigen	Mus musculus	0-5
32923114-8	2020	We found PD-L1 expression was modulated by MEK-ERK pathway signaling in both parental and Crizotinib-resistant NSCLC cells with ROS1 fusion.	Crizotinib	90-100	CD274 antigen	Mus musculus	9-14
32923114-8	2020	We found PD-L1 expression was modulated by MEK-ERK pathway signaling in both parental and Crizotinib-resistant NSCLC cells with ROS1 fusion.	Crizotinib	90-100	midkine	Mus musculus	43-46
32923114-8	2020	We found PD-L1 expression was modulated by MEK-ERK pathway signaling in both parental and Crizotinib-resistant NSCLC cells with ROS1 fusion.	Crizotinib	90-100	mitogen-activated protein kinase 1	Mus musculus	47-50
32923114-8	2020	We found PD-L1 expression was modulated by MEK-ERK pathway signaling in both parental and Crizotinib-resistant NSCLC cells with ROS1 fusion.	Crizotinib	90-100	Ros1 proto-oncogene	Mus musculus	128-132
32923114-9	2020	Conclusions: The correlation between ROS1-fusion and PD-L1 overexpression suggested that PD-L1/PD-1 blockade could be the second-line treatment option for the Crizotinib-resistant NSCLC with ROS1 rearrangement.	Crizotinib	159-169	Ros1 proto-oncogene	Mus musculus	37-41
32923114-9	2020	Conclusions: The correlation between ROS1-fusion and PD-L1 overexpression suggested that PD-L1/PD-1 blockade could be the second-line treatment option for the Crizotinib-resistant NSCLC with ROS1 rearrangement.	Crizotinib	159-169	CD274 antigen	Mus musculus	53-58
32923114-9	2020	Conclusions: The correlation between ROS1-fusion and PD-L1 overexpression suggested that PD-L1/PD-1 blockade could be the second-line treatment option for the Crizotinib-resistant NSCLC with ROS1 rearrangement.	Crizotinib	159-169	CD274 antigen	Mus musculus	89-94
32923114-9	2020	Conclusions: The correlation between ROS1-fusion and PD-L1 overexpression suggested that PD-L1/PD-1 blockade could be the second-line treatment option for the Crizotinib-resistant NSCLC with ROS1 rearrangement.	Crizotinib	159-169	programmed cell death 1	Mus musculus	95-99
32923114-9	2020	Conclusions: The correlation between ROS1-fusion and PD-L1 overexpression suggested that PD-L1/PD-1 blockade could be the second-line treatment option for the Crizotinib-resistant NSCLC with ROS1 rearrangement.	Crizotinib	159-169	Ros1 proto-oncogene	Mus musculus	191-195
32167664-0	2020	First-line crizotinib versus platinum-pemetrexed chemotherapy in patients with advanced ROS1-rearranged non-small-cell lung cancer.	Crizotinib	11-21	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	88-92
32167664-1	2020	OBJECTIVES: Food and Drug Administration (FDA) approved crizotinib for advanced ROS1-rearranged (ROS1+) non-small-cell lung cancer (NSCLC) patients due to a single-arm study PROFILE 1001.	Crizotinib	56-66	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	80-84
32167664-1	2020	OBJECTIVES: Food and Drug Administration (FDA) approved crizotinib for advanced ROS1-rearranged (ROS1+) non-small-cell lung cancer (NSCLC) patients due to a single-arm study PROFILE 1001.	Crizotinib	56-66	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	97-101
32167664-12	2020	CONCLUSIONS: Our results suggested that first-line crizotinib had higher ORR and longer PFS than platinum-pemetrexed chemotherapy in patients with advanced ROS1+NSCLC, but the differences were not observed for OS.	Crizotinib	51-61	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	156-160
32168429-0	2020	Crizotinib vs platinum-based chemotherapy as first-line treatment for advanced non-small cell lung cancer with different ROS1 fusion variants.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	121-125
32168429-2	2020	Crizotinib is recommended for ROS1-positive NSCLC due to its favorable outcome in published clinical trials.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	30-34
32168429-8	2020	In patients harboring CD74 fusion variants, the median PFS with first-line crizotinib treatment was significantly longer than in those harboring non-CD74 fusion variants (20.1 months vs 12.0 months, respectively; P = .046).	Crizotinib	75-85	CD74 molecule	Homo sapiens	22-26
32168429-11	2020	CONCLUSIONS: First-line therapy with crizotinib is more beneficial than platinum-based chemotherapy in patients with advanced NSCLC with different ROS1 fusion variants.	Crizotinib	37-47	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	147-151
32168429-12	2020	Patients harboring CD74 fusion variants appear to respond better to crizotinib.	Crizotinib	68-78	CD74 molecule	Homo sapiens	19-23
32410828-10	2020	Numerous drugs were found exerting their anti-tumor function through Id1-related signaling pathways, such as fucoidan, berberine, tetramethylpyrazine, crizotinib, cannabidiol and vinblastine.	Crizotinib	151-161	inhibitor of DNA binding 1, HLH protein	Homo sapiens	69-72
32208297-7	2020	In vitro experiments using patient-derived cells bearing concurrent CD74-ROS1-rearrangement and ROS1 G2032 K demonstrated half-maximal inhibitory concentration IC50 of 730.2 nM for lorlatinib, 812.1 nM for entrectinib, and 1546 nM for crizotinib, indicating resistance to these inhibitors.	Crizotinib	235-245	CD74 molecule	Homo sapiens	68-72
32208297-7	2020	In vitro experiments using patient-derived cells bearing concurrent CD74-ROS1-rearrangement and ROS1 G2032 K demonstrated half-maximal inhibitory concentration IC50 of 730.2 nM for lorlatinib, 812.1 nM for entrectinib, and 1546 nM for crizotinib, indicating resistance to these inhibitors.	Crizotinib	235-245	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	96-100
32272316-2	2020	Detection of the anaplastic lymphoma kinase (ALK) gene rearrangement has great predictive value for treatment with small molecule tyrosine kinase inhibitor (crizotinib and alectinib commonly).	Crizotinib	157-167	ALK receptor tyrosine kinase	Homo sapiens	17-43
32272316-2	2020	Detection of the anaplastic lymphoma kinase (ALK) gene rearrangement has great predictive value for treatment with small molecule tyrosine kinase inhibitor (crizotinib and alectinib commonly).	Crizotinib	157-167	ALK receptor tyrosine kinase	Homo sapiens	45-48
32325863-3	2020	We observed significant clinical benefit by the first three ALK-TKIs (Crizotinib, Ceritinib, Alectinib) and chemotherapy with Pemetrexed, resulting in overall survival over 3 years.	Crizotinib	70-80	ALK receptor tyrosine kinase	Homo sapiens	60-63
32238411-0	2020	Crizotinib in ROS1 and MET Deregulated NSCLC-Letter.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	14-18
32238412-0	2020	Crizotinib in ROS1 and MET Deregulated NSCLC-Response.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	14-18
32114282-0	2020	A novel SOS1-ALK fusion variant in a patient with metastatic lung adenocarcinoma and a remarkable response to crizotinib.	Crizotinib	110-120	SOS Ras/Rac guanine nucleotide exchange factor 1	Homo sapiens	8-12
32296229-3	2020	Patients with advanced NSCLC having anaplastic lymphoma kinase (ALK) fusion protein are sensitive to ALK inhibitors such as crizotinib.	Crizotinib	124-134	ALK receptor tyrosine kinase	Homo sapiens	36-62
32296229-3	2020	Patients with advanced NSCLC having anaplastic lymphoma kinase (ALK) fusion protein are sensitive to ALK inhibitors such as crizotinib.	Crizotinib	124-134	ALK receptor tyrosine kinase	Homo sapiens	64-67
32296229-3	2020	Patients with advanced NSCLC having anaplastic lymphoma kinase (ALK) fusion protein are sensitive to ALK inhibitors such as crizotinib.	Crizotinib	124-134	ALK receptor tyrosine kinase	Homo sapiens	101-104
32296229-4	2020	This study aimed to further explore the clinicopathological characteristics of postoperative patients with early-stage lung cancer harboring ALK fusion protein and provide a basis to carry out postoperative adjuvant crizotinib treatment.	Crizotinib	216-226	ALK receptor tyrosine kinase	Homo sapiens	141-144
32296229-9	2020	Postoperative adjuvant crizotinib treatment for patients with stage IIIA NSCLC harboring ALK fusion protein is promising.	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	89-92
32114282-0	2020	A novel SOS1-ALK fusion variant in a patient with metastatic lung adenocarcinoma and a remarkable response to crizotinib.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	13-16
32114282-2	2020	Currently, crizotinib is the standard first-line treatment for ALK-positive NSCLC.	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	63-66
32232958-1	2020	Crizotinib (XALKORI  ) is indicated for anaplastic lymphoma kinase-positive and ROS1-positive advanced non-small cell lung cancer.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	80-84
32420077-4	2020	We present the case of a 52-year-old man who was diagnosed with an ALK-positive NSCLC and was treated with crizotinib and, subsequently, ceritinib.	Crizotinib	107-117	ALK receptor tyrosine kinase	Homo sapiens	67-70
32420077-5	2020	The analysis of serial liquid biopsies by NGS detected two asynchronous mutations arising in the ALK locus during disease progression, namely p.Gly1269Ala (c.3806G>C) and p.Gly1202Arg (c.3604G>A), that conferred resistance to crizotinib and ceritinib, respectively.	Crizotinib	226-236	ALK receptor tyrosine kinase	Homo sapiens	97-100
32228679-6	2020	Oral crizotinib 250 mg BID will be administered until disease progression or unacceptable toxicity.	Crizotinib	5-15	BH3 interacting domain death agonist	Homo sapiens	23-26
32143435-3	2020	In this study, we designed a prodrug strategy for the approved c-MET, ALK, and ROS1 tyrosine kinase inhibitor crizotinib.	Crizotinib	110-120	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	63-68
32214855-1	2020	Background: Crizotinib is the first tyrosine kinase inhibitor approved for the treatment of anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	92-118
32214855-1	2020	Background: Crizotinib is the first tyrosine kinase inhibitor approved for the treatment of anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	120-123
32214855-3	2020	Case Presentation: We herein report the case of a 74-year-old woman who received crizotinib for metastatic ALK-positive NSCLC.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	107-110
32164629-0	2020	Alteration in the sensitivity to crizotinib by Na+/H+ exchanger regulatory factor 1 is dependent to its subcellular localization in ALK-positive lung cancers.	Crizotinib	33-43	SLC9A3 regulator 1	Homo sapiens	47-83
32164629-0	2020	Alteration in the sensitivity to crizotinib by Na+/H+ exchanger regulatory factor 1 is dependent to its subcellular localization in ALK-positive lung cancers.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	132-135
32164629-3	2020	Anaplastic lymphoma kinase (ALK) fusion mutations are validated molecules targeted therapy in lung cancers, where crizotinib can be used as the specific inhibitor to suppress tumor progression.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	0-26
32164629-3	2020	Anaplastic lymphoma kinase (ALK) fusion mutations are validated molecules targeted therapy in lung cancers, where crizotinib can be used as the specific inhibitor to suppress tumor progression.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	28-31
32164629-4	2020	However, due to the less frequent occurrence of ALK mutations and the complexity for factors to determine drug responses, the genes that could alter crizotinib sensitivity are unclear.	Crizotinib	149-159	ALK receptor tyrosine kinase	Homo sapiens	48-51
32164629-6	2020	The possible mechanisms of NHERF1 and its role in the cell sensitivity to crizotinib were investigated using an ALK-positive and crizotinib-sensitive lung adenocarcinoma cell line H3122.	Crizotinib	74-84	SLC9A3 regulator 1	Homo sapiens	27-33
32164629-9	2020	NHERF1 expression in ALK positive lung cancer cells was regulated by ALK activities, and was in return able to alter the sensitivity to crizotinib.	Crizotinib	136-146	SLC9A3 regulator 1	Homo sapiens	0-6
32164629-9	2020	NHERF1 expression in ALK positive lung cancer cells was regulated by ALK activities, and was in return able to alter the sensitivity to crizotinib.	Crizotinib	136-146	ALK receptor tyrosine kinase	Homo sapiens	21-24
32164629-10	2020	The function of NHERF1 to influence crizotinib sensitivity was depending on its subcellular distribution in cytosol instead of its nucleus localized form.	Crizotinib	36-46	SLC9A3 regulator 1	Homo sapiens	16-22
32164629-12	2020	The determination of NHERF1 levels in ALK positive NSCLC tissues might be useful to predict crizotinib resistance, especially by distinguishing cytosolic or nuclear localized NHERF1 for the overexpressed molecules.	Crizotinib	92-102	SLC9A3 regulator 1	Homo sapiens	21-27
32164629-12	2020	The determination of NHERF1 levels in ALK positive NSCLC tissues might be useful to predict crizotinib resistance, especially by distinguishing cytosolic or nuclear localized NHERF1 for the overexpressed molecules.	Crizotinib	92-102	ALK receptor tyrosine kinase	Homo sapiens	38-41
31630357-6	2020	The composed outcomes (the sum of PFS or TTF) in patients treated with crizotinib followed by a new generation ALKis were 27.8 months [CI 95% 24.3-33.7] in PFS and 30.4 months [CI 95% 24.7-34.9] in TTF.	Crizotinib	71-81	ras homolog family member H	Homo sapiens	41-44
31630357-6	2020	The composed outcomes (the sum of PFS or TTF) in patients treated with crizotinib followed by a new generation ALKis were 27.8 months [CI 95% 24.3-33.7] in PFS and 30.4 months [CI 95% 24.7-34.9] in TTF.	Crizotinib	71-81	ras homolog family member H	Homo sapiens	198-201
31156053-0	2020	An advanced c-MET-amplified NSCLC patient that was treated with crizotinib.	Crizotinib	64-74	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	12-17
31156053-5	2020	CASE REPORT: We present a metastatic c-MET-amplified non-small cell lung cancer (NSCLC) patient who was treated with crizotinib.	Crizotinib	117-127	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	37-42
31156053-7	2020	MANAGEMENT AND OUTCOME: After c-MET amplification was shown, crizotinib 250 mg BID was started.	Crizotinib	61-71	BH3 interacting domain death agonist	Homo sapiens	79-82
32093861-0	2020	Melanoregulin-Anaplastic Lymphoma Kinase (ALK), a Novel ALK Rearrangement That Responds to Crizotinib in Lung Adenocarcinoma.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	0-40
32093861-0	2020	Melanoregulin-Anaplastic Lymphoma Kinase (ALK), a Novel ALK Rearrangement That Responds to Crizotinib in Lung Adenocarcinoma.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	42-45
32093861-0	2020	Melanoregulin-Anaplastic Lymphoma Kinase (ALK), a Novel ALK Rearrangement That Responds to Crizotinib in Lung Adenocarcinoma.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	56-59
32111984-6	2020	In addition, SOX13 was shown to be a direct target of HGF/STAT3 signaling, and the c-MET inhibitor crizotinib blocked the HGF/STAT3/SOX13/c-MET axis, significantly inhibiting SOX13-mediated CRC migration, invasion and metastasis.	Crizotinib	99-109	hepatocyte growth factor	Homo sapiens	54-57
32111984-6	2020	In addition, SOX13 was shown to be a direct target of HGF/STAT3 signaling, and the c-MET inhibitor crizotinib blocked the HGF/STAT3/SOX13/c-MET axis, significantly inhibiting SOX13-mediated CRC migration, invasion and metastasis.	Crizotinib	99-109	signal transducer and activator of transcription 3	Homo sapiens	58-63
32111984-6	2020	In addition, SOX13 was shown to be a direct target of HGF/STAT3 signaling, and the c-MET inhibitor crizotinib blocked the HGF/STAT3/SOX13/c-MET axis, significantly inhibiting SOX13-mediated CRC migration, invasion and metastasis.	Crizotinib	99-109	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	83-88
32111984-6	2020	In addition, SOX13 was shown to be a direct target of HGF/STAT3 signaling, and the c-MET inhibitor crizotinib blocked the HGF/STAT3/SOX13/c-MET axis, significantly inhibiting SOX13-mediated CRC migration, invasion and metastasis.	Crizotinib	99-109	hepatocyte growth factor	Homo sapiens	122-125
32111984-6	2020	In addition, SOX13 was shown to be a direct target of HGF/STAT3 signaling, and the c-MET inhibitor crizotinib blocked the HGF/STAT3/SOX13/c-MET axis, significantly inhibiting SOX13-mediated CRC migration, invasion and metastasis.	Crizotinib	99-109	signal transducer and activator of transcription 3	Homo sapiens	126-131
32111984-6	2020	In addition, SOX13 was shown to be a direct target of HGF/STAT3 signaling, and the c-MET inhibitor crizotinib blocked the HGF/STAT3/SOX13/c-MET axis, significantly inhibiting SOX13-mediated CRC migration, invasion and metastasis.	Crizotinib	99-109	SRY-box transcription factor 13	Homo sapiens	132-137
32111984-6	2020	In addition, SOX13 was shown to be a direct target of HGF/STAT3 signaling, and the c-MET inhibitor crizotinib blocked the HGF/STAT3/SOX13/c-MET axis, significantly inhibiting SOX13-mediated CRC migration, invasion and metastasis.	Crizotinib	99-109	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	138-143
32111984-6	2020	In addition, SOX13 was shown to be a direct target of HGF/STAT3 signaling, and the c-MET inhibitor crizotinib blocked the HGF/STAT3/SOX13/c-MET axis, significantly inhibiting SOX13-mediated CRC migration, invasion and metastasis.	Crizotinib	99-109	SRY-box transcription factor 13	Homo sapiens	132-137
32111984-9	2020	In summary, SOX13 is a promising prognostic biomarker in patients with CRC, and blocking the HGF/STAT3/SOX13/c-MET axis with crizotinib could be a new therapeutic strategy to prevent SOX13-mediated CRC metastasis.	Crizotinib	125-135	hepatocyte growth factor	Homo sapiens	93-96
32111984-9	2020	In summary, SOX13 is a promising prognostic biomarker in patients with CRC, and blocking the HGF/STAT3/SOX13/c-MET axis with crizotinib could be a new therapeutic strategy to prevent SOX13-mediated CRC metastasis.	Crizotinib	125-135	signal transducer and activator of transcription 3	Homo sapiens	97-102
32111984-9	2020	In summary, SOX13 is a promising prognostic biomarker in patients with CRC, and blocking the HGF/STAT3/SOX13/c-MET axis with crizotinib could be a new therapeutic strategy to prevent SOX13-mediated CRC metastasis.	Crizotinib	125-135	SRY-box transcription factor 13	Homo sapiens	103-108
32111984-9	2020	In summary, SOX13 is a promising prognostic biomarker in patients with CRC, and blocking the HGF/STAT3/SOX13/c-MET axis with crizotinib could be a new therapeutic strategy to prevent SOX13-mediated CRC metastasis.	Crizotinib	125-135	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	109-114
32111984-9	2020	In summary, SOX13 is a promising prognostic biomarker in patients with CRC, and blocking the HGF/STAT3/SOX13/c-MET axis with crizotinib could be a new therapeutic strategy to prevent SOX13-mediated CRC metastasis.	Crizotinib	125-135	SRY-box transcription factor 13	Homo sapiens	103-108
30985604-0	2020	Tumor Volume Analysis as a Predictive Marker for Prolonged Survival in Anaplastic Lymphoma Kinase-rearranged Advanced Non-Small Cell Lung Cancer Patients Treated With Crizotinib.	Crizotinib	167-177	ALK receptor tyrosine kinase	Homo sapiens	71-97
30985604-2	2020	We performed tumor volume analysis of ALK-rearranged advanced NSCLC treated with crizotinib to identify an early predictive marker for prolonged survival.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	38-41
30985604-9	2020	CONCLUSIONS: The 8-week tumor volume decrease of >74% is significantly associated with longer OS in patients with ALK-rearranged NSCLC treated with crizotinib.	Crizotinib	148-158	ALK receptor tyrosine kinase	Homo sapiens	114-117
32020234-8	2020	Importantly, this pro-tumorigenic effect was completely abolished by the ALK-specific inhibitor crizotinib, indicating the potential effectiveness of ALK-specific inhibitors in treating ALK-rearranged ccRCC patients.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	73-76
32020234-8	2020	Importantly, this pro-tumorigenic effect was completely abolished by the ALK-specific inhibitor crizotinib, indicating the potential effectiveness of ALK-specific inhibitors in treating ALK-rearranged ccRCC patients.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	150-153
32020234-8	2020	Importantly, this pro-tumorigenic effect was completely abolished by the ALK-specific inhibitor crizotinib, indicating the potential effectiveness of ALK-specific inhibitors in treating ALK-rearranged ccRCC patients.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	150-153
32143435-3	2020	In this study, we designed a prodrug strategy for the approved c-MET, ALK, and ROS1 tyrosine kinase inhibitor crizotinib.	Crizotinib	110-120	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	79-83
32158297-3	2020	Fortunately, crizotinib, an ALK1 tyrosine-kinase inhibitor, provides long-term disease control.	Crizotinib	13-23	secretory leukocyte peptidase inhibitor	Homo sapiens	28-32
32158297-11	2020	Fourteen of the 20 patients with ROS1-gene rearrangement received crizotinib therapy, with an objective response rate of 64.28%.	Crizotinib	66-76	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	33-37
32158297-13	2020	Conclusion: ROS1-gene rearrangement was present at a relatively higher frequency of 2.8% in north Indian patients with lung adenocarcinoma and was successfully targeted by crizotinib therapy.	Crizotinib	172-182	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	12-16
32133282-0	2020	CT-Based Radiomic Signature as a Prognostic Factor in Stage IV ALK-Positive Non-small-cell Lung Cancer Treated With TKI Crizotinib: A Proof-of-Concept Study.	Crizotinib	120-130	ALK receptor tyrosine kinase	Homo sapiens	63-66
32133282-1	2020	Objectives: To identify a computed tomography (CT)-based radiomic signature for predicting progression-free survival (PFS) in stage IV anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitor (TKI) crizotinib.	Crizotinib	266-276	ALK receptor tyrosine kinase	Homo sapiens	163-166
32195033-6	2020	In this study, we show that hyperactivated c-Met is detected in TNBC cells with acquired resistance to PARPi, and the combination of talazoparib and crizotinib (a multi-kinase inhibitor that inhibits c-MET) synergistically inhibits proliferation in these cells.	Crizotinib	149-159	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	43-48
32055239-2	2020	Although ALK mutations can reliably predict the likelihood of response to ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, they cannot reliably predict response duration or intrinsic/extrinsic therapeutic resistance.	Crizotinib	120-130	ALK receptor tyrosine kinase	Homo sapiens	9-12
32055239-2	2020	Although ALK mutations can reliably predict the likelihood of response to ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, they cannot reliably predict response duration or intrinsic/extrinsic therapeutic resistance.	Crizotinib	120-130	ALK receptor tyrosine kinase	Homo sapiens	74-77
32055239-3	2020	To further refine the application of personalized medicine in this indication, this study aimed to identify prognostic proteomic biomarkers in ALK fusion positive NSCLC patients to crizotinib.	Crizotinib	181-191	ALK receptor tyrosine kinase	Homo sapiens	143-146
32055239-4	2020	Methods: Twenty-four patients with advanced NSCLC harboring ALK fusion were administered crizotinib in a phase IV trial which included blood sampling prior to treatment.	Crizotinib	89-99	ALK receptor tyrosine kinase	Homo sapiens	60-63
32055239-9	2020	Finally, by integrating the different analytic methods, we selected 22 proteins as potential candidates for a blood-based prognostic signature of response to crizotinib in NSCLC patients harboring ALK fusion.	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	197-200
32055239-10	2020	Conclusion: In conjunction with ALK mutation, the expression of this proteomic signature may represent a liquid biopsy-based marker of long-term response to crizotinib in NSCLC.	Crizotinib	157-167	ALK receptor tyrosine kinase	Homo sapiens	32-35
32195033-6	2020	In this study, we show that hyperactivated c-Met is detected in TNBC cells with acquired resistance to PARPi, and the combination of talazoparib and crizotinib (a multi-kinase inhibitor that inhibits c-MET) synergistically inhibits proliferation in these cells.	Crizotinib	149-159	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	200-205
33102632-0	2020	Tumor volume dynamics and tumor growth rate in ALK-rearranged advanced non-small-cell lung cancer treated with crizotinib.	Crizotinib	111-121	ALK receptor tyrosine kinase	Homo sapiens	47-50
32060867-7	2020	RESULTS: Fifty-nine patients received crizotinib as their only prior ALK TKI (EXP2-3A); cumulative incidence rates (CIRs) of CNS and non-CNS progression were both 22% at 12 months in patients with baseline CNS metastases (n = 37), and CIR of non-CNS progression at 12 months was higher versus that for CNS progression in patients without baseline CNS metastases [43% vs. 9% (n = 22)].	Crizotinib	38-48	corepressor interacting with RBPJ, CIR1	Homo sapiens	116-119
33102632-1	2020	Purpose: The purpose of the study is to investigate volumetric tumor burden dynamics and tumor growth rates in ALK-rearranged advanced NSCLC patients during crizotinib monotherapy.	Crizotinib	157-167	ALK receptor tyrosine kinase	Homo sapiens	111-114
33102632-8	2020	Conclusions: Tumor volume growth rate after nadir in ALK-rearranged NSCLC patients treated with crizotinib was obtained, providing objective reference values that can inform physicians when deciding to keep their patients on ALK directed therapy with slowly progressing lung cancer.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	53-56
33102632-8	2020	Conclusions: Tumor volume growth rate after nadir in ALK-rearranged NSCLC patients treated with crizotinib was obtained, providing objective reference values that can inform physicians when deciding to keep their patients on ALK directed therapy with slowly progressing lung cancer.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	225-228
31740393-0	2020	Drug-drug interaction between crizotinib and entecavir via renal secretory transporter OCT2.	Crizotinib	30-40	solute carrier family 22 member 2	Homo sapiens	87-91
31740393-9	2020	Kinetic constants for crizotinib uptake by OCT2 were Km 1.16 +- 0.26 microM, Vmax 12.05 +- 0.53 micromol/min mg-1 protein and Ki 9.711 nM.	Crizotinib	22-32	solute carrier family 22 member 2	Homo sapiens	43-47
31740393-9	2020	Kinetic constants for crizotinib uptake by OCT2 were Km 1.16 +- 0.26 microM, Vmax 12.05 +- 0.53 micromol/min mg-1 protein and Ki 9.711 nM.	Crizotinib	22-32	mucin 5B, oligomeric mucus/gel-forming	Homo sapiens	109-113
31740393-10	2020	Entecavir can inhibit crizotinib transport by OCT2 in kidney.	Crizotinib	22-32	solute carrier family 22 member 2	Homo sapiens	46-50
33307508-3	2020	Among the pretreatment options of patients diagnosed with EML4-ALK rearrangement, is crizotinib.	Crizotinib	85-95	EMAP like 4	Homo sapiens	58-62
33307508-3	2020	Among the pretreatment options of patients diagnosed with EML4-ALK rearrangement, is crizotinib.	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	63-66
31628085-1	2020	BACKGROUND: Ensartinib is a potent new-generation ALK inhibitor with high activity against a broad range of known crizotinib-resistant ALK mutations and CNS metastases.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	50-53
31628085-1	2020	BACKGROUND: Ensartinib is a potent new-generation ALK inhibitor with high activity against a broad range of known crizotinib-resistant ALK mutations and CNS metastases.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	135-138
31809977-0	2020	Clinical response to crizotinib and emergence of resistance in lung adenocarcinoma harboring a MET c-Cbl binding site mutation.	Crizotinib	21-31	SAFB like transcription modulator	Homo sapiens	95-98
31809977-0	2020	Clinical response to crizotinib and emergence of resistance in lung adenocarcinoma harboring a MET c-Cbl binding site mutation.	Crizotinib	21-31	Cbl proto-oncogene	Homo sapiens	101-104
31809977-3	2020	RESULTS: We report the case of a patient with metastastic lung adenocarcinoma harboring a c-Cbl binding site alteration and demonstrate clinical, radiological and metabolic response to crizotinib with a PFS of 10.6 months.	Crizotinib	185-195	Cbl proto-oncogene	Homo sapiens	90-95
31932802-0	2020	Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration.	Crizotinib	22-32	SAFB like transcription modulator	Homo sapiens	61-64
31932802-9	2020	MET exon 14 alteration defines a molecular subgroup of NSCLCs for which MET inhibition with crizotinib is active.	Crizotinib	92-102	SAFB like transcription modulator	Homo sapiens	0-3
31932802-9	2020	MET exon 14 alteration defines a molecular subgroup of NSCLCs for which MET inhibition with crizotinib is active.	Crizotinib	92-102	SAFB like transcription modulator	Homo sapiens	72-75
32460299-0	2020	Does Crizotinib Auto-Inhibit CYP3A in vivo?	Crizotinib	5-15	cytochrome P450, family 3, subfamily a, polypeptide 11	Mus musculus	29-34
32460299-2	2020	There is in vitro evidence that crizotinib may auto-inhibit cytochrome P450 3A (CYP3A) activity, with important implications for crizotinib pharmacokinetics.	Crizotinib	32-42	cytochrome P450, family 3, subfamily a, polypeptide 11	Mus musculus	60-78
32460299-2	2020	There is in vitro evidence that crizotinib may auto-inhibit cytochrome P450 3A (CYP3A) activity, with important implications for crizotinib pharmacokinetics.	Crizotinib	32-42	cytochrome P450, family 3, subfamily a, polypeptide 11	Mus musculus	80-85
32460299-2	2020	There is in vitro evidence that crizotinib may auto-inhibit cytochrome P450 3A (CYP3A) activity, with important implications for crizotinib pharmacokinetics.	Crizotinib	129-139	cytochrome P450, family 3, subfamily a, polypeptide 11	Mus musculus	80-85
31480046-1	2020	Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor that was approved for ALK-harboring lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	17-43
31480046-1	2020	Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor that was approved for ALK-harboring lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	45-48
31480046-1	2020	Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor that was approved for ALK-harboring lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	82-85
31419130-2	2019	Currently, five small-molecule inhibitors of ALK, including Crizotinib, Ceritinib, Alectinib, Brigatinib, and Lorlatinib, have been approved by the U.S. Food and Drug Administration (FDA) against ALK-positive NSCLCs.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	45-48
31416808-0	2019	Crizotinib in MET-Deregulated or ROS1-Rearranged Pretreated Non-Small Cell Lung Cancer (METROS): A Phase II, Prospective, Multicenter, Two-Arms Trial.	Crizotinib	0-10	SAFB like transcription modulator	Homo sapiens	14-17
31416808-0	2019	Crizotinib in MET-Deregulated or ROS1-Rearranged Pretreated Non-Small Cell Lung Cancer (METROS): A Phase II, Prospective, Multicenter, Two-Arms Trial.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	33-37
31416808-2	2019	Although recent studies have suggested a potential role for crizotinib in patients harboring MET amplification or exon 14 mutations, no conclusive data are currently available.	Crizotinib	60-70	SAFB like transcription modulator	Homo sapiens	93-96
31416808-3	2019	This study aimed at investigating activity of crizotinib in patients harboring MET or ROS1 alterations.	Crizotinib	46-56	SAFB like transcription modulator	Homo sapiens	79-82
31416808-3	2019	This study aimed at investigating activity of crizotinib in patients harboring MET or ROS1 alterations.	Crizotinib	46-56	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	86-90
31416808-12	2019	CONCLUSIONS: Crizotinib induces response in a fraction of MET-deregulated NSCLC.	Crizotinib	13-23	SAFB like transcription modulator	Homo sapiens	58-61
31753813-4	2019	Here, we report the case of a KLC1-ALK-rearranged NSCLC patient responding to crizotinib treatment and demonstrate how analysis of plasma and serum biomarkers can be used to identify the ALK fusion partner and monitor therapy over time.	Crizotinib	78-88	kinesin light chain 1	Homo sapiens	30-34
31753813-4	2019	Here, we report the case of a KLC1-ALK-rearranged NSCLC patient responding to crizotinib treatment and demonstrate how analysis of plasma and serum biomarkers can be used to identify the ALK fusion partner and monitor therapy over time.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	35-38
31753813-4	2019	Here, we report the case of a KLC1-ALK-rearranged NSCLC patient responding to crizotinib treatment and demonstrate how analysis of plasma and serum biomarkers can be used to identify the ALK fusion partner and monitor therapy over time.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	187-190
31827192-2	2019	Crizotinib, a first generation ALK-TKI, has superiority to standard chemotherapy with longer progression-free survival and higher objective response rate.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	31-34
31607443-4	2020	PATIENTS AND METHODS: The METROS trial is a prospective phase II study designed to assess efficacy, safety, and tolerability of crizotinib in patients with pre-treated metastatic NSCLC ROS1 rearrangement (cohort A) or with MET amplification or MET exon 14 mutation (cohort B).	Crizotinib	128-138	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	185-189
31778074-0	2020	Dose-escalation trial of the ALK, MET & ROS1 inhibitor, crizotinib, in patients with advanced cancer.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	29-32
31778074-0	2020	Dose-escalation trial of the ALK, MET & ROS1 inhibitor, crizotinib, in patients with advanced cancer.	Crizotinib	56-66	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	40-44
31740393-1	2020	Both entecavir and crizotinib are substrates of organic cation transporter 2 (OCT2).	Crizotinib	19-29	solute carrier family 22 member 2	Homo sapiens	48-76
31740393-1	2020	Both entecavir and crizotinib are substrates of organic cation transporter 2 (OCT2).	Crizotinib	19-29	solute carrier family 22 member 2	Homo sapiens	78-82
31401883-2	2019	We performed SAR study of pyrazolo[3,4-b]pyridines to override crizotinib resistance caused by ALK-L1196M mutation and identified a novel and potent L1196M inhibitor, 10g.	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	95-98
31584608-0	2019	Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSe phase II trial.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	14-19
31584608-0	2019	Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSe phase II trial.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	24-28
31109722-2	2019	First-line therapies for metastatic NSCLC such as crizotinib, a tyrosine kinase inhibitor (TKI), have developed resistance due to a rearrangement of the anaplastic lymphoma kinase (ALK) gene.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	153-179
31109722-2	2019	First-line therapies for metastatic NSCLC such as crizotinib, a tyrosine kinase inhibitor (TKI), have developed resistance due to a rearrangement of the anaplastic lymphoma kinase (ALK) gene.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	181-184
31757376-0	2019	Coexistence of a Novel PRKCB-ALK, EML4-ALK Double-Fusion in a Lung Adenocarcinoma Patient and Response to Crizotinib.	Crizotinib	106-116	protein kinase C beta	Homo sapiens	23-28
31630043-0	2019	ALK immunohistochemistry positive, FISH negative NSCLC is infrequent, but associated with impaired survival following treatment with crizotinib.	Crizotinib	133-143	ALK receptor tyrosine kinase	Homo sapiens	0-3
31757376-0	2019	Coexistence of a Novel PRKCB-ALK, EML4-ALK Double-Fusion in a Lung Adenocarcinoma Patient and Response to Crizotinib.	Crizotinib	106-116	ALK receptor tyrosine kinase	Homo sapiens	39-42
31446643-5	2019	AZD9291 resistance was partially restored by combination of AZD9291 and crizotinib only in resistant cells overexpressing phospho-c-Met, which synergistically inhibited c-Met-mediated phosphorylation of the downstream targets ERK1/2 and AKT.	Crizotinib	72-82	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	130-135
31768065-3	2019	In this study, we uncovered activating mutations in CSF1R and rearrangements in RET and ALK that conferred dramatic responses to selective inhibition of RET (selpercatinib) and crizotinib, respectively, in patients with histiocytosis.	Crizotinib	177-187	ret proto-oncogene	Homo sapiens	80-83
31768065-3	2019	In this study, we uncovered activating mutations in CSF1R and rearrangements in RET and ALK that conferred dramatic responses to selective inhibition of RET (selpercatinib) and crizotinib, respectively, in patients with histiocytosis.	Crizotinib	177-187	ALK receptor tyrosine kinase	Homo sapiens	88-91
31699471-0	2019	Clinical observation of crizotinib in the treatment of ALK-positive advanced non-small cell lung cancer.	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	55-58
31699471-3	2019	RESULTS: Of the 87 ALK-positive-patients, 47 patients were treated with oral administration of crizotinib.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	19-22
31727555-3	2019	Several inhibitors of the tyrosine kinase of ALK (crizotinib, ceritinib, alectinib) have been approved as first line therapies in patients with advanced ALK positive NSCLC, which are associated with a better median progression-free survival than conventional chemotherapy.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	45-48
31727555-3	2019	Several inhibitors of the tyrosine kinase of ALK (crizotinib, ceritinib, alectinib) have been approved as first line therapies in patients with advanced ALK positive NSCLC, which are associated with a better median progression-free survival than conventional chemotherapy.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	153-156
31023173-0	2019	Complete remission for 4 years with crizotinib in advanced ALK-positive non-small cell lung cancer after thoracostomy for empyema.	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	59-62
31023173-2	2019	Crizotinib (tyrosine kinase inhibitor) has been considered as the standard of care for advanced ALK-positive lung cancer but it only gives a median progression-free survival of 7.7-11 months.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	96-99
31023173-5	2019	After confirmation of the ALK translocation, therapy with crizotinib was started.	Crizotinib	58-68	ALK receptor tyrosine kinase	Homo sapiens	26-29
31439588-8	2019	RESULTS: Multiple mutations in various genes in ALK-independent pathways were predominantly identified in CTCs of crizotinib-resistant patients.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	48-51
31768065-3	2019	In this study, we uncovered activating mutations in CSF1R and rearrangements in RET and ALK that conferred dramatic responses to selective inhibition of RET (selpercatinib) and crizotinib, respectively, in patients with histiocytosis.	Crizotinib	177-187	colony stimulating factor 1 receptor	Homo sapiens	52-57
31613427-2	2019	Crizotinib and ceritinib have demonstrated superior efficacy to platinum-based chemotherapy as front-line treatment for patients with ALK-positive advanced non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	134-137
31425908-0	2019	Novel derivatives of anaplastic lymphoma kinase inhibitors: Synthesis, radiolabeling, and preliminary biological studies of fluoroethyl analogues of crizotinib, alectinib, and ceritinib.	Crizotinib	149-159	ALK receptor tyrosine kinase	Homo sapiens	21-47
31425908-2	2019	Although several ALK inhibitors, including crizotinib, ceritinib, and alectinib, are approved for cancer treatment, their long-term benefit is often limited by the cancer"s acquisition of resistance owing to secondary point mutations in ALK.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	17-20
31425908-2	2019	Although several ALK inhibitors, including crizotinib, ceritinib, and alectinib, are approved for cancer treatment, their long-term benefit is often limited by the cancer"s acquisition of resistance owing to secondary point mutations in ALK.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	237-240
31639374-1	2019	Crizotinib is an oral small-molecule tyrosine kinase inhibitor targeting anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) and MET proto-oncogene, receptor tyrosine kinase (MET).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	73-99
31639374-1	2019	Crizotinib is an oral small-molecule tyrosine kinase inhibitor targeting anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) and MET proto-oncogene, receptor tyrosine kinase (MET).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	101-104
31639374-1	2019	Crizotinib is an oral small-molecule tyrosine kinase inhibitor targeting anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) and MET proto-oncogene, receptor tyrosine kinase (MET).	Crizotinib	0-10	ret proto-oncogene	Homo sapiens	129-153
31639374-1	2019	Crizotinib is an oral small-molecule tyrosine kinase inhibitor targeting anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) and MET proto-oncogene, receptor tyrosine kinase (MET).	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	155-159
31639374-1	2019	Crizotinib is an oral small-molecule tyrosine kinase inhibitor targeting anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) and MET proto-oncogene, receptor tyrosine kinase (MET).	Crizotinib	0-10	ret proto-oncogene	Homo sapiens	185-209
31639374-1	2019	Crizotinib is an oral small-molecule tyrosine kinase inhibitor targeting anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) and MET proto-oncogene, receptor tyrosine kinase (MET).	Crizotinib	0-10	SAFB like transcription modulator	Homo sapiens	165-168
31639374-6	2019	Importantly, crizotinib induced hepatocyte apoptosis independent of its targets, ALK, ROS1 and MET.	Crizotinib	13-23	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	86-90
31639374-6	2019	Importantly, crizotinib induced hepatocyte apoptosis independent of its targets, ALK, ROS1 and MET.	Crizotinib	13-23	SAFB like transcription modulator	Homo sapiens	95-98
31639374-7	2019	In conclusion, our data showed that crizotinib induced liver injury through hepatocyte death via the apoptotic pathway which was independent of ALK, ROS1 and MET.	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	144-147
31639374-7	2019	In conclusion, our data showed that crizotinib induced liver injury through hepatocyte death via the apoptotic pathway which was independent of ALK, ROS1 and MET.	Crizotinib	36-46	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	149-153
31717403-6	2019	In vitro pharmacological profiling led to the conclusion that that crizotinib-GnRH conjugates are transported directly into lysosomes, where the membrane permeability of crizotinib is diminished.	Crizotinib	67-77	gonadotropin releasing hormone 1	Homo sapiens	78-82
31717403-6	2019	In vitro pharmacological profiling led to the conclusion that that crizotinib-GnRH conjugates are transported directly into lysosomes, where the membrane permeability of crizotinib is diminished.	Crizotinib	170-180	gonadotropin releasing hormone 1	Homo sapiens	78-82
31717403-7	2019	As a consequence of GnRHR-mediated endocytosis, GnRH-conjugated crizotinib bypasses its molecular targets-the ATP-binding site of RTKs- and is sequestered in the lysosomes.	Crizotinib	64-74	gonadotropin releasing hormone receptor	Homo sapiens	20-25
31717403-7	2019	As a consequence of GnRHR-mediated endocytosis, GnRH-conjugated crizotinib bypasses its molecular targets-the ATP-binding site of RTKs- and is sequestered in the lysosomes.	Crizotinib	64-74	gonadotropin releasing hormone 1	Homo sapiens	20-24
31717403-8	2019	These results explained the lower efficacy of crizotinib-GnRH conjugates in EBC-1 cells, and led to the conclusion that drug escape from the lysosomes is a major challenge in the development of clinically relevant anti-cancer drug-GnRH conjugates.	Crizotinib	46-56	gonadotropin releasing hormone 1	Homo sapiens	57-61
31717403-8	2019	These results explained the lower efficacy of crizotinib-GnRH conjugates in EBC-1 cells, and led to the conclusion that drug escape from the lysosomes is a major challenge in the development of clinically relevant anti-cancer drug-GnRH conjugates.	Crizotinib	46-56	gonadotropin releasing hormone 1	Homo sapiens	231-235
31250326-1	2019	We present the case of an old woman with ALK-rearranged stage IV lung adenocarcinoma who received crizotinib.	Crizotinib	98-108	ALK receptor tyrosine kinase	Homo sapiens	41-44
31446643-5	2019	AZD9291 resistance was partially restored by combination of AZD9291 and crizotinib only in resistant cells overexpressing phospho-c-Met, which synergistically inhibited c-Met-mediated phosphorylation of the downstream targets ERK1/2 and AKT.	Crizotinib	72-82	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	169-174
31446643-5	2019	AZD9291 resistance was partially restored by combination of AZD9291 and crizotinib only in resistant cells overexpressing phospho-c-Met, which synergistically inhibited c-Met-mediated phosphorylation of the downstream targets ERK1/2 and AKT.	Crizotinib	72-82	mitogen-activated protein kinase 3	Homo sapiens	226-232
31446643-5	2019	AZD9291 resistance was partially restored by combination of AZD9291 and crizotinib only in resistant cells overexpressing phospho-c-Met, which synergistically inhibited c-Met-mediated phosphorylation of the downstream targets ERK1/2 and AKT.	Crizotinib	72-82	AKT serine/threonine kinase 1	Homo sapiens	237-240
31382035-1	2019	Clinical data confirmed that patients with ROS1 rearrangement are sensitive to specific inhibitors, such as crizotinib.	Crizotinib	108-118	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	43-47
31362880-1	2019	BACKGROUND: Central nervous system (CNS) progression is a common manifestation of acquired resistance to crizotinib in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC).	Crizotinib	105-115	ALK receptor tyrosine kinase	Homo sapiens	119-145
31362880-1	2019	BACKGROUND: Central nervous system (CNS) progression is a common manifestation of acquired resistance to crizotinib in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC).	Crizotinib	105-115	ALK receptor tyrosine kinase	Homo sapiens	147-150
31407528-0	2019	Treatment duration as a surrogate endpoint to evaluate the efficacy of crizotinib in sequential therapy for patients with advanced ALK-positive non-small cell lung cancer: A retrospective, real-world study.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	131-134
31374369-6	2019	RESULTS: ABC-14 cells harbored no ALK mutations and were sensitive to crizotinib while also exhibiting MNNG HOS transforming gene (MET) gene amplification and amphiregulin overexpression.	Crizotinib	70-80	ATP binding cassette subfamily B member 6 (Langereis blood group)	Homo sapiens	9-15
31521978-0	2019	The clinical responses of TNIP2-ALK fusion variants to crizotinib in ALK-rearranged lung adenocarcinoma.	Crizotinib	55-65	TNFAIP3 interacting protein 2	Homo sapiens	26-31
31521978-0	2019	The clinical responses of TNIP2-ALK fusion variants to crizotinib in ALK-rearranged lung adenocarcinoma.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	32-35
31521978-0	2019	The clinical responses of TNIP2-ALK fusion variants to crizotinib in ALK-rearranged lung adenocarcinoma.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	69-72
31521978-4	2019	Herein, we described a rare case of ALK-rearranged lung adenocarcinoma responding to crizotinib.	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	36-39
31521978-8	2019	CONCLUSION: This case provides valuable information on the response to crizotinib of patients with TNIP2-ALK fusion and better understanding of ALK-TKI applications in the future.	Crizotinib	71-81	TNFAIP3 interacting protein 2	Homo sapiens	99-104
31521978-8	2019	CONCLUSION: This case provides valuable information on the response to crizotinib of patients with TNIP2-ALK fusion and better understanding of ALK-TKI applications in the future.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	105-108
31256210-4	2019	Crizotinib is a small-molecule tyrosine kinase inhibitor (TKI) which was discovered to actively inhibit ALK, MET, and ROS1.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	104-107
31256210-4	2019	Crizotinib is a small-molecule tyrosine kinase inhibitor (TKI) which was discovered to actively inhibit ALK, MET, and ROS1.	Crizotinib	0-10	SAFB like transcription modulator	Homo sapiens	109-112
31256210-4	2019	Crizotinib is a small-molecule tyrosine kinase inhibitor (TKI) which was discovered to actively inhibit ALK, MET, and ROS1.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	118-122
31256210-5	2019	Crizotinib has shown to be remarkably efficacious against ROS1 lung cancer, prompting ROS1 detection in lung cancer to be quite significant.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	58-62
31256210-5	2019	Crizotinib has shown to be remarkably efficacious against ROS1 lung cancer, prompting ROS1 detection in lung cancer to be quite significant.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	86-90
31256210-6	2019	Sadly, crizotinib resistance in ROS1 is a frequent occurrence which poses a major clinical challenge in the successful treatment of ROS1 lung cancer; hence, the discovery of the second and third generation ROS1 inhibitors is of utmost importance.	Crizotinib	7-17	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	32-36
31256210-6	2019	Sadly, crizotinib resistance in ROS1 is a frequent occurrence which poses a major clinical challenge in the successful treatment of ROS1 lung cancer; hence, the discovery of the second and third generation ROS1 inhibitors is of utmost importance.	Crizotinib	7-17	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	132-136
31256210-6	2019	Sadly, crizotinib resistance in ROS1 is a frequent occurrence which poses a major clinical challenge in the successful treatment of ROS1 lung cancer; hence, the discovery of the second and third generation ROS1 inhibitors is of utmost importance.	Crizotinib	7-17	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	132-136
31256210-7	2019	In this review, we discuss the underlying mechanisms through which ROS1 tumor cells acquire resistance to crizotinib-the first-line drug for ROS1-positive NSCLC, and summarize various new potent drugs which can overcome this resistance and serve as viable alternatives.	Crizotinib	106-116	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	67-71
31256210-7	2019	In this review, we discuss the underlying mechanisms through which ROS1 tumor cells acquire resistance to crizotinib-the first-line drug for ROS1-positive NSCLC, and summarize various new potent drugs which can overcome this resistance and serve as viable alternatives.	Crizotinib	106-116	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	141-145
31407528-1	2019	OBJECTIVES: Crizotinib has demonstrated good efficacy in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	71-97
31407528-1	2019	OBJECTIVES: Crizotinib has demonstrated good efficacy in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	99-102
31407528-12	2019	CONCLUSIONS: Crizotinib showed good efficacy in patients with ALK-positive advanced NSCLC.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	62-65
31260890-0	2019	Design, synthesis and biological evaluations of 2-amino-4-(1-piperidine) pyridine derivatives as novel anti crizotinib-resistant ALK/ROS1 dual inhibitors.	Crizotinib	108-118	ALK receptor tyrosine kinase	Homo sapiens	129-132
31720561-5	2019	On the basis of impressive progression-free survival of 19.2 months from the PROFILE 1001 trial, crizotinib obtained Food and Drug Administration (FDA) approval as first-line therapy for treatment of ROS1+ NSCLC.	Crizotinib	97-107	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	200-204
31260890-0	2019	Design, synthesis and biological evaluations of 2-amino-4-(1-piperidine) pyridine derivatives as novel anti crizotinib-resistant ALK/ROS1 dual inhibitors.	Crizotinib	108-118	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	133-137
31260890-1	2019	ALK and ROS1 kinases have become promising therapeutic targets since Crizotinib was used to treat non-small-cell lung cancer clinically.	Crizotinib	69-79	ALK receptor tyrosine kinase	Homo sapiens	0-3
31260890-1	2019	ALK and ROS1 kinases have become promising therapeutic targets since Crizotinib was used to treat non-small-cell lung cancer clinically.	Crizotinib	69-79	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	8-12
31260890-7	2019	Furthermore, molecular modeling disclosed that all the representative inhibitors could dock into the active site of ALK and ROS1, which gave a probable explanation of anti Crizotinib-resistant mutants.	Crizotinib	172-182	anaplastic lymphoma kinase	Mus musculus	116-119
31260890-7	2019	Furthermore, molecular modeling disclosed that all the representative inhibitors could dock into the active site of ALK and ROS1, which gave a probable explanation of anti Crizotinib-resistant mutants.	Crizotinib	172-182	Ros1 proto-oncogene	Mus musculus	124-128
31260890-8	2019	These results indicated that our work has established a path forward for the generation of anti Crizotinib-resistant ALK/ROS1 dual inhibitors.	Crizotinib	96-106	anaplastic lymphoma kinase	Mus musculus	117-120
31260890-8	2019	These results indicated that our work has established a path forward for the generation of anti Crizotinib-resistant ALK/ROS1 dual inhibitors.	Crizotinib	96-106	Ros1 proto-oncogene	Mus musculus	121-125
30940295-1	2019	ROS1 rearrangements define a distinct molecular subset of non-small-cell lung cancer (NSCLC), which can be treated effectively with crizotinib, a tyrosine kinase inhibitor (TKI) targeting ROS1/MET/ALK rearrangements.	Crizotinib	132-142	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	0-4
31491676-1	2019	OBJECTIVES: Brigatinib is a next-generation ALK inhibitor initially developed in ALK-positive NSCLC pretreated with crizotinib.	Crizotinib	116-126	ALK receptor tyrosine kinase	Homo sapiens	44-47
31608224-0	2019	The Impact of Clinical Factors, ALK Fusion Variants, and BIM Polymorphism on Crizotinib-Treated Advanced EML4-ALK Rearranged Non-small Cell Lung Cancer.	Crizotinib	77-87	EMAP like 4	Homo sapiens	105-109
31608224-0	2019	The Impact of Clinical Factors, ALK Fusion Variants, and BIM Polymorphism on Crizotinib-Treated Advanced EML4-ALK Rearranged Non-small Cell Lung Cancer.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	110-113
31608224-1	2019	Patients" clinical factors and genetics factors such as anaplastic lymphoma kinase (ALK) fusion variants and BIM (Bcl-2-like 11) polymorphism were reported to be associated with clinical outcome in crizotinib-treated advanced non-small cell lung cancer (NSCLC).	Crizotinib	198-208	ALK receptor tyrosine kinase	Homo sapiens	56-82
31608224-1	2019	Patients" clinical factors and genetics factors such as anaplastic lymphoma kinase (ALK) fusion variants and BIM (Bcl-2-like 11) polymorphism were reported to be associated with clinical outcome in crizotinib-treated advanced non-small cell lung cancer (NSCLC).	Crizotinib	198-208	ALK receptor tyrosine kinase	Homo sapiens	84-87
31608224-1	2019	Patients" clinical factors and genetics factors such as anaplastic lymphoma kinase (ALK) fusion variants and BIM (Bcl-2-like 11) polymorphism were reported to be associated with clinical outcome in crizotinib-treated advanced non-small cell lung cancer (NSCLC).	Crizotinib	198-208	BCL2 like 11	Homo sapiens	114-127
31608224-3	2019	We analyzed outcome of 54 patients with known ALK fusion variants who received crizotinib for advanced NSCLC.	Crizotinib	79-89	ALK receptor tyrosine kinase	Homo sapiens	46-49
31178493-1	2019	Crizotinib has been approved for patients with advanced lung adenocarcinoma harboring rearrangements of the c-ROS-1 (ROS1) and anaplastic lymphoma kinase (ALK) genes.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	108-115
31178493-1	2019	Crizotinib has been approved for patients with advanced lung adenocarcinoma harboring rearrangements of the c-ROS-1 (ROS1) and anaplastic lymphoma kinase (ALK) genes.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	117-121
31178493-1	2019	Crizotinib has been approved for patients with advanced lung adenocarcinoma harboring rearrangements of the c-ROS-1 (ROS1) and anaplastic lymphoma kinase (ALK) genes.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	127-153
31178493-1	2019	Crizotinib has been approved for patients with advanced lung adenocarcinoma harboring rearrangements of the c-ROS-1 (ROS1) and anaplastic lymphoma kinase (ALK) genes.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	155-158
31564978-0	2019	Elevated levels of pre-treatment lactate dehydrogenase are an unfavorable predictor factor in patients with EML4-ALK rearrangement non-small cell lung cancer treated with crizotinib.	Crizotinib	171-181	EMAP like 4	Homo sapiens	108-112
31564978-0	2019	Elevated levels of pre-treatment lactate dehydrogenase are an unfavorable predictor factor in patients with EML4-ALK rearrangement non-small cell lung cancer treated with crizotinib.	Crizotinib	171-181	ALK receptor tyrosine kinase	Homo sapiens	113-116
31564978-2	2019	We performed a retrospective analysis to investigate the association between the lactate dehydrogenase (LDH) levels and progression-free survival (PFS) in patients with EML4-ALK rearrangement NSCLC receiving treatment with crizotinib.	Crizotinib	223-233	EMAP like 4	Homo sapiens	169-173
31564978-2	2019	We performed a retrospective analysis to investigate the association between the lactate dehydrogenase (LDH) levels and progression-free survival (PFS) in patients with EML4-ALK rearrangement NSCLC receiving treatment with crizotinib.	Crizotinib	223-233	ALK receptor tyrosine kinase	Homo sapiens	174-177
31564978-3	2019	Methods: Advanced (stage IIIb-IV) NSCLC patients with EML4-ALK rearrangement receiving treatment with crizotinib were enrolled between January 2007 and January 2016 at Peking Union Medical College and Cancer Hospital Chinese Academy of Medical Sciences.	Crizotinib	102-112	EMAP like 4	Homo sapiens	54-58
31564978-3	2019	Methods: Advanced (stage IIIb-IV) NSCLC patients with EML4-ALK rearrangement receiving treatment with crizotinib were enrolled between January 2007 and January 2016 at Peking Union Medical College and Cancer Hospital Chinese Academy of Medical Sciences.	Crizotinib	102-112	ALK receptor tyrosine kinase	Homo sapiens	59-62
30499816-7	2019	Therapeutic responses were observed in 5 of 10 crizotinib-treated patients including 1 patient with ALK FISH+ IHC- status and 1 patient with ALK FISH- IHC+ status.	Crizotinib	47-57	ALK receptor tyrosine kinase	Homo sapiens	100-103
30499816-7	2019	Therapeutic responses were observed in 5 of 10 crizotinib-treated patients including 1 patient with ALK FISH+ IHC- status and 1 patient with ALK FISH- IHC+ status.	Crizotinib	47-57	ALK receptor tyrosine kinase	Homo sapiens	141-144
31331844-4	2019	Unfortunately in the first year on crizotinib, the pioneering ALK inhibitors, approximately one third of these patients fail in the central nervous system, which is explained by an inadequate central nervous system drug penetration through the blood-brain barrier.	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	62-65
31331844-8	2019	The next generation ALK inhibitors were designed to cross the blood-brain barrier more efficiently than crizotinib and achieve higher concentration in the cerebrospinal fluid, offering prominent ability to control central nervous system spread.	Crizotinib	104-114	ALK receptor tyrosine kinase	Homo sapiens	20-23
31307938-0	2019	Response to Crizotinib Re-administration After Progression on Lorlatinib in a Patient With ALK-rearranged Non-small-cell Lung Cancer.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	91-94
31445731-0	2019	A Novel Intergenic Region between CENPA and DPYSL5-ALK Exon 20 Fusion Variant Responding to Crizotinib Treatment in a Patient with Lung Adenocarcinoma.	Crizotinib	92-102	centromere protein A	Homo sapiens	34-39
31445731-0	2019	A Novel Intergenic Region between CENPA and DPYSL5-ALK Exon 20 Fusion Variant Responding to Crizotinib Treatment in a Patient with Lung Adenocarcinoma.	Crizotinib	92-102	dihydropyrimidinase like 5	Homo sapiens	44-50
31447007-1	2019	OBJECTIVES: Patients harboring rearrangements of the ROS1 gene are eligible for first-line therapy with Crizotinib, which represents the best available treatment option.	Crizotinib	104-114	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	53-57
31447007-3	2019	However, the probability of response to Crizotinib in patients with 5" deletion in ROS1 is unknown given the rarity of this condition.	Crizotinib	40-50	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	83-87
31447007-6	2019	CONCLUSION: 5" ROS1 deletions detected by FISH are associated with a high chance of response to Crizotinib in NSCLC, similarly to canonical ROS1 split-apart FISH rearrangements.	Crizotinib	96-106	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	15-19
31396389-0	2019	Long-term complete response in a patient with postoperative recurrent ALK-rearranged lung adenocarcinoma treated with crizotinib: A case report.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	70-73
31396389-3	2019	Herein we present a case of variant type 2 ALK-rearranged lung adenocarcinoma recurrence with multiple lung metastasis that maintained complete response over 5 years with crizotinib, which is the first approved ALK inhibitor.	Crizotinib	171-181	ALK receptor tyrosine kinase	Homo sapiens	43-46
31396389-3	2019	Herein we present a case of variant type 2 ALK-rearranged lung adenocarcinoma recurrence with multiple lung metastasis that maintained complete response over 5 years with crizotinib, which is the first approved ALK inhibitor.	Crizotinib	171-181	ALK receptor tyrosine kinase	Homo sapiens	211-214
31396389-4	2019	The efficacy of crizotinib may vary among ALK fusion variants and thus, variant type may represent an important factor in guiding the treatment strategy for ALK-rearranged lung adenocarcinoma.	Crizotinib	16-26	ALK receptor tyrosine kinase	Homo sapiens	42-45
31396389-4	2019	The efficacy of crizotinib may vary among ALK fusion variants and thus, variant type may represent an important factor in guiding the treatment strategy for ALK-rearranged lung adenocarcinoma.	Crizotinib	16-26	ALK receptor tyrosine kinase	Homo sapiens	157-160
31454018-10	2019	In patients with overexpression of ALK protein, the response rate was significantly better with crizotinib (a tyrosine kinase inhibitor) than with the combination of pemetrexed and either cisplatin or carboplatin (platinum-based chemotherapy) (74% vs 45%, respectively; P < .001) and progression-free survival (median, 10.9 months vs 7.0 months; P < .001).	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	35-38
31451138-0	2019	[Efficacy and Safety of Crizotinib in Advanced or Recurrent  : ALK-positive Non-small Cell Lung Cancer].	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	63-66
31451138-2	2019	The aim of this study is to evaluate the efficacy and safety of crizotinib in patients with advanced ALK gene-positive or recurrent NSCLC.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	101-104
31451138-4	2019	The patients with ALK positive tested by flourescence in situ hybridization (FISH) was given orally crizotinib, 250 mg, bid.	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	18-21
31451138-9	2019	CONCLUSIONS: Crizotinib can be used for the treatment of advanced NSCLC with ALK fusion/translocation.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	77-80
31399568-0	2019	The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models.	Crizotinib	68-78	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	29-33
31399568-0	2019	The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models.	Crizotinib	68-78	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	89-93
31399568-2	2019	Crizotinib, an ALK/ROS1/MET inhibitor, is highly effective against ROS1-rearranged lung cancer and is used in clinic.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	15-18
31399568-2	2019	Crizotinib, an ALK/ROS1/MET inhibitor, is highly effective against ROS1-rearranged lung cancer and is used in clinic.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	19-23
31399568-3	2019	However, crizotinib resistance is an emerging issue, and several resistance mechanisms, such as secondary kinase-domain mutations (e.g., ROS1-G2032R) have been identified in crizotinib-refractory patients.	Crizotinib	174-184	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	137-141
31399568-6	2019	Here we report that DS-6051b is effective in treating ROS1- or NTRK-rearranged cancer in preclinical models, including crizotinib-resistant ROS1 positive cancer with secondary kinase domain mutations especially G2032R mutation which is highly resistant to crizotinib as well as lorlatinib and entrectinib, next generation ROS1 inhibitors.	Crizotinib	119-129	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	140-144
31399568-6	2019	Here we report that DS-6051b is effective in treating ROS1- or NTRK-rearranged cancer in preclinical models, including crizotinib-resistant ROS1 positive cancer with secondary kinase domain mutations especially G2032R mutation which is highly resistant to crizotinib as well as lorlatinib and entrectinib, next generation ROS1 inhibitors.	Crizotinib	119-129	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	140-144
30940295-0	2019	Different Types of ROS1 Fusion Partners Yield Comparable Efficacy to Crizotinib.	Crizotinib	69-79	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	19-23
31382924-0	2019	ROS1-ADGRG6: a case report of a novel ROS1 oncogenic fusion variant in lung adenocarcinoma and the response to crizotinib.	Crizotinib	111-121	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	0-4
31382924-0	2019	ROS1-ADGRG6: a case report of a novel ROS1 oncogenic fusion variant in lung adenocarcinoma and the response to crizotinib.	Crizotinib	111-121	adhesion G protein-coupled receptor G6	Homo sapiens	5-11
31382924-0	2019	ROS1-ADGRG6: a case report of a novel ROS1 oncogenic fusion variant in lung adenocarcinoma and the response to crizotinib.	Crizotinib	111-121	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	38-42
31382924-3	2019	The ALK inhibitor (crizotinib) exhibits therapeutic effect against ROS1-rearranged NSCLC.	Crizotinib	19-29	ALK receptor tyrosine kinase	Homo sapiens	4-7
31382924-3	2019	The ALK inhibitor (crizotinib) exhibits therapeutic effect against ROS1-rearranged NSCLC.	Crizotinib	19-29	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	67-71
31388026-0	2019	Molecular Modeling of ALK L1198F and/or G1202R Mutations to Determine Differential Crizotinib Sensitivity.	Crizotinib	83-93	ALK receptor tyrosine kinase	Homo sapiens	22-25
31388026-1	2019	Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that has been recognized as a therapeutic target for EML4-ALK fusion-positive nonsmall cell lung cancer (NSCLC) treatment using type I kinase inhibitors such as crizotinib to take over the ATP binding site.	Crizotinib	224-234	ALK receptor tyrosine kinase	Homo sapiens	0-26
31388026-1	2019	Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that has been recognized as a therapeutic target for EML4-ALK fusion-positive nonsmall cell lung cancer (NSCLC) treatment using type I kinase inhibitors such as crizotinib to take over the ATP binding site.	Crizotinib	224-234	ALK receptor tyrosine kinase	Homo sapiens	28-31
31388026-1	2019	Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that has been recognized as a therapeutic target for EML4-ALK fusion-positive nonsmall cell lung cancer (NSCLC) treatment using type I kinase inhibitors such as crizotinib to take over the ATP binding site.	Crizotinib	224-234	EMAP like 4	Homo sapiens	116-120
31388026-1	2019	Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that has been recognized as a therapeutic target for EML4-ALK fusion-positive nonsmall cell lung cancer (NSCLC) treatment using type I kinase inhibitors such as crizotinib to take over the ATP binding site.	Crizotinib	224-234	ALK receptor tyrosine kinase	Homo sapiens	121-124
31388026-2	2019	According to Shaw"s measurements, ALK carrying G1202R mutation shows reduced response to crizotinib (IC50 = 382 nM vs. IC50 = 20 nM for wild-type), whereas L1198F mutant is more responsive (IC50 = 0.4 nM).	Crizotinib	89-99	ALK receptor tyrosine kinase	Homo sapiens	34-37
31388026-8	2019	These results demonstrated how the mutated residues tune the crizotinib response and may assist kinase inhibitor development especially for ALK G1202R, analogous to the ROS1 G2302R and MET G1163R mutations that are also resistant to crizotinib treatment in NSCLC.	Crizotinib	61-71	ALK receptor tyrosine kinase	Homo sapiens	140-143
31388026-8	2019	These results demonstrated how the mutated residues tune the crizotinib response and may assist kinase inhibitor development especially for ALK G1202R, analogous to the ROS1 G2302R and MET G1163R mutations that are also resistant to crizotinib treatment in NSCLC.	Crizotinib	61-71	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	169-173
31388026-8	2019	These results demonstrated how the mutated residues tune the crizotinib response and may assist kinase inhibitor development especially for ALK G1202R, analogous to the ROS1 G2302R and MET G1163R mutations that are also resistant to crizotinib treatment in NSCLC.	Crizotinib	233-243	ALK receptor tyrosine kinase	Homo sapiens	140-143
31388026-8	2019	These results demonstrated how the mutated residues tune the crizotinib response and may assist kinase inhibitor development especially for ALK G1202R, analogous to the ROS1 G2302R and MET G1163R mutations that are also resistant to crizotinib treatment in NSCLC.	Crizotinib	233-243	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	169-173
31305295-1	2019	The second-generation ALK tyrosine kinase inhibitor brigatinib has recently been approved in the European Union for use after crizotinib treatment in patients with EML4-ALK-rearranged lung cancer.	Crizotinib	126-136	ALK receptor tyrosine kinase	Homo sapiens	22-25
31078602-0	2019	Decrease in phospho-PRAS40 plays a role in the synergy between erlotinib and crizotinib in an EGFR and cMET wild-type squamous non-small cell lung cancer cell line.	Crizotinib	77-87	AKT1 substrate 1	Homo sapiens	20-26
31078602-0	2019	Decrease in phospho-PRAS40 plays a role in the synergy between erlotinib and crizotinib in an EGFR and cMET wild-type squamous non-small cell lung cancer cell line.	Crizotinib	77-87	epidermal growth factor receptor	Homo sapiens	94-98
31078602-0	2019	Decrease in phospho-PRAS40 plays a role in the synergy between erlotinib and crizotinib in an EGFR and cMET wild-type squamous non-small cell lung cancer cell line.	Crizotinib	77-87	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	103-107
31209157-1	2019	Patients with non-small cell lung cancer harboring MET exon 14 skipping mutations have commonly been treated with the multikinase inhibitor crizotinib, but more MET-specific therapies are being developed.	Crizotinib	140-150	SAFB like transcription modulator	Homo sapiens	51-54
31313100-0	2019	Targeting ROS1 Rearrangements in Non-small Cell Lung Cancer: Crizotinib and Newer Generation Tyrosine Kinase Inhibitors.	Crizotinib	61-71	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	10-14
31313100-3	2019	Crizotinib was the first tyrosine kinase inhibitor to demonstrate activity in ROS1-rearranged lung cancer, and remains the recommended first-line therapy for patients with advanced ROS1-rearranged non-small cell lung cancer.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	78-82
31313100-3	2019	Crizotinib was the first tyrosine kinase inhibitor to demonstrate activity in ROS1-rearranged lung cancer, and remains the recommended first-line therapy for patients with advanced ROS1-rearranged non-small cell lung cancer.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	181-185
31313100-6	2019	In this review, we discuss ROS1 rearrangements in non-small cell lung cancer, and provide an update on targeting ROS1-rearranged non-small cell lung cancer with crizotinib and newer generation tyrosine kinase inhibitors.	Crizotinib	161-171	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	113-117
31717403-0	2019	Novel Crizotinib-GnRH Conjugates Revealed the Significance of Lysosomal Trapping in GnRH-Based Drug Delivery Systems.	Crizotinib	6-16	gonadotropin releasing hormone 1	Homo sapiens	17-21
31717403-0	2019	Novel Crizotinib-GnRH Conjugates Revealed the Significance of Lysosomal Trapping in GnRH-Based Drug Delivery Systems.	Crizotinib	6-16	gonadotropin releasing hormone 1	Homo sapiens	84-88
31717403-2	2019	Crizotinib is an effective multi-target kinase inhibitor, approved against anaplastic lymphoma kinase (ALK)- or ROS proto-oncogene 1 (ROS-1)-positive non-small cell lung carcinoma (NSCLC); however, its application is accompanied by serious side effects.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	75-101
31717403-2	2019	Crizotinib is an effective multi-target kinase inhibitor, approved against anaplastic lymphoma kinase (ALK)- or ROS proto-oncogene 1 (ROS-1)-positive non-small cell lung carcinoma (NSCLC); however, its application is accompanied by serious side effects.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	103-106
31717403-2	2019	Crizotinib is an effective multi-target kinase inhibitor, approved against anaplastic lymphoma kinase (ALK)- or ROS proto-oncogene 1 (ROS-1)-positive non-small cell lung carcinoma (NSCLC); however, its application is accompanied by serious side effects.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	134-139
31717403-4	2019	Our most prominent crizotinib-GnRH conjugates, the amide-bond-containing [d-Lys6(crizotinib*)]-GnRH-I and the ester-bond-containing [d-Lys6(MJ55*)]-GnRH-I, were able to bind to GnRH-receptor (GnRHR) and exert a potent c-Met kinase inhibitory effect.	Crizotinib	19-29	gonadotropin releasing hormone 1	Homo sapiens	30-34
31717403-4	2019	Our most prominent crizotinib-GnRH conjugates, the amide-bond-containing [d-Lys6(crizotinib*)]-GnRH-I and the ester-bond-containing [d-Lys6(MJ55*)]-GnRH-I, were able to bind to GnRH-receptor (GnRHR) and exert a potent c-Met kinase inhibitory effect.	Crizotinib	19-29	gonadotropin releasing hormone receptor	Homo sapiens	177-190
31717403-4	2019	Our most prominent crizotinib-GnRH conjugates, the amide-bond-containing [d-Lys6(crizotinib*)]-GnRH-I and the ester-bond-containing [d-Lys6(MJ55*)]-GnRH-I, were able to bind to GnRH-receptor (GnRHR) and exert a potent c-Met kinase inhibitory effect.	Crizotinib	19-29	gonadotropin releasing hormone receptor	Homo sapiens	192-197
31717403-4	2019	Our most prominent crizotinib-GnRH conjugates, the amide-bond-containing [d-Lys6(crizotinib*)]-GnRH-I and the ester-bond-containing [d-Lys6(MJ55*)]-GnRH-I, were able to bind to GnRH-receptor (GnRHR) and exert a potent c-Met kinase inhibitory effect.	Crizotinib	19-29	SAFB like transcription modulator	Homo sapiens	220-223
31391294-0	2019	MET Genomic Alterations in Head and Neck Squamous Cell Carcinoma (HNSCC): Rapid Response to Crizotinib in a Patient with HNSCC with a Novel MET R1004G Mutation.	Crizotinib	92-102	SAFB like transcription modulator	Homo sapiens	0-3
31391294-0	2019	MET Genomic Alterations in Head and Neck Squamous Cell Carcinoma (HNSCC): Rapid Response to Crizotinib in a Patient with HNSCC with a Novel MET R1004G Mutation.	Crizotinib	92-102	SAFB like transcription modulator	Homo sapiens	140-143
31391294-3	2019	The patient was treated with the oral MET tyrosine kinase inhibitor crizotinib with rapid response to treatment.Based on this index case, we determined the frequency of MET alterations in 1,637 HNSCC samples, which had been analyzed with hybrid capture-based CGP performed in the routine course of clinical care.	Crizotinib	68-78	SAFB like transcription modulator	Homo sapiens	38-41
31391294-3	2019	The patient was treated with the oral MET tyrosine kinase inhibitor crizotinib with rapid response to treatment.Based on this index case, we determined the frequency of MET alterations in 1,637 HNSCC samples, which had been analyzed with hybrid capture-based CGP performed in the routine course of clinical care.	Crizotinib	68-78	SAFB like transcription modulator	Homo sapiens	169-172
31391294-7	2019	KEY POINTS: This case report is believed to be the first reported pan-cancer case of a patient harboring a MET mutation at R1004 demonstrating a clinical response to crizotinib, in addition to the first documented case of head and neck squamous cell carcinoma (HNSCC) with any MET alteration responding to crizotinib.The positive response to MET inhibition in this patient highlights the significance of comprehensive genomic profiling in advanced metastatic HNSCC to identify actionable targetable molecular alterations as current treatment options are limited.	Crizotinib	166-176	SAFB like transcription modulator	Homo sapiens	107-110
31391294-7	2019	KEY POINTS: This case report is believed to be the first reported pan-cancer case of a patient harboring a MET mutation at R1004 demonstrating a clinical response to crizotinib, in addition to the first documented case of head and neck squamous cell carcinoma (HNSCC) with any MET alteration responding to crizotinib.The positive response to MET inhibition in this patient highlights the significance of comprehensive genomic profiling in advanced metastatic HNSCC to identify actionable targetable molecular alterations as current treatment options are limited.	Crizotinib	166-176	SAFB like transcription modulator	Homo sapiens	277-280
31391294-7	2019	KEY POINTS: This case report is believed to be the first reported pan-cancer case of a patient harboring a MET mutation at R1004 demonstrating a clinical response to crizotinib, in addition to the first documented case of head and neck squamous cell carcinoma (HNSCC) with any MET alteration responding to crizotinib.The positive response to MET inhibition in this patient highlights the significance of comprehensive genomic profiling in advanced metastatic HNSCC to identify actionable targetable molecular alterations as current treatment options are limited.	Crizotinib	166-176	SAFB like transcription modulator	Homo sapiens	277-280
31391294-7	2019	KEY POINTS: This case report is believed to be the first reported pan-cancer case of a patient harboring a MET mutation at R1004 demonstrating a clinical response to crizotinib, in addition to the first documented case of head and neck squamous cell carcinoma (HNSCC) with any MET alteration responding to crizotinib.The positive response to MET inhibition in this patient highlights the significance of comprehensive genomic profiling in advanced metastatic HNSCC to identify actionable targetable molecular alterations as current treatment options are limited.	Crizotinib	306-316	SAFB like transcription modulator	Homo sapiens	107-110
31506424-5	2019	We therefore explored novel treatment strategies using clinically approved drugs afatinib (ERBB family inhibitor) and crizotinib (MET inhibitor), to simultaneously block MET and ERBB family RTKs.	Crizotinib	118-128	epidermal growth factor receptor	Homo sapiens	178-182
31506424-12	2019	In summary, our results show that afatinib and crizotinib in combination is a promising alternative targeted therapy option for CMM patients, irrespective of BRAF/NRAS mutational status, as well as for cases where resistance has developed towards BRAF inhibitors.	Crizotinib	47-57	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	158-162
31506424-12	2019	In summary, our results show that afatinib and crizotinib in combination is a promising alternative targeted therapy option for CMM patients, irrespective of BRAF/NRAS mutational status, as well as for cases where resistance has developed towards BRAF inhibitors.	Crizotinib	47-57	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	247-251
31125274-18	2019	Both algorithms suggested that brigatinib improved health utility in crizotinib-refractory ALK + NSCLC patients, and improvements were maintained during most of the treatment.	Crizotinib	69-79	ALK receptor tyrosine kinase	Homo sapiens	91-94
29950554-0	2019	Clinical factors affecting progression-free survival with crizotinib in ALK-positive non-small cell lung cancer.	Crizotinib	58-68	ALK receptor tyrosine kinase	Homo sapiens	72-75
29950554-1	2019	BACKGROUND/AIMS: Although crizotinib is standard chemotherapy for advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), clinical factors affecting progression-free survival (PFS) have not been reported.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	75-101
29950554-1	2019	BACKGROUND/AIMS: Although crizotinib is standard chemotherapy for advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), clinical factors affecting progression-free survival (PFS) have not been reported.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	103-106
29950554-10	2019	CONCLUSION: Performance status, number of metastatic organs, and response to crizotinib affected PFS of crizotinib in ALK-positive NSCLC.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	118-121
29950554-10	2019	CONCLUSION: Performance status, number of metastatic organs, and response to crizotinib affected PFS of crizotinib in ALK-positive NSCLC.	Crizotinib	104-114	ALK receptor tyrosine kinase	Homo sapiens	118-121
31243098-2	2019	Here, we present a comprehensive genomic landscape of 11 patients with ALK+ NSCLC and investigate its relationship with response to crizotinib.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	71-74
30940295-1	2019	ROS1 rearrangements define a distinct molecular subset of non-small-cell lung cancer (NSCLC), which can be treated effectively with crizotinib, a tyrosine kinase inhibitor (TKI) targeting ROS1/MET/ALK rearrangements.	Crizotinib	132-142	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	188-192
30940295-1	2019	ROS1 rearrangements define a distinct molecular subset of non-small-cell lung cancer (NSCLC), which can be treated effectively with crizotinib, a tyrosine kinase inhibitor (TKI) targeting ROS1/MET/ALK rearrangements.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	197-200
30790150-3	2019	Crizotinib, a first-generation ALK inhibitor, has been shown to have a notable response in patients with ALK-positive IMT.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	31-34
30790150-3	2019	Crizotinib, a first-generation ALK inhibitor, has been shown to have a notable response in patients with ALK-positive IMT.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	105-108
31345341-0	2019	Retroperitoneal Pseudotumor Induced by Crizotinib Treatment for c-MET exon 14 Skip Mutation NCSLC.	Crizotinib	39-49	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	64-69
31339066-0	2019	Crizotinib-resistant MET mutations in gastric cancer patients are sensitive to type II tyrosine kinase inhibitors.	Crizotinib	0-10	SAFB like transcription modulator	Homo sapiens	21-24
31339066-1	2019	Aim: Crizotinib has been used to counter MET amplification in different human malignancies.	Crizotinib	5-15	SAFB like transcription modulator	Homo sapiens	41-44
31339066-5	2019	Results: Four MET mutations conferred resistance to crizotinib with sustained activation of downstream signaling pathways of MET.	Crizotinib	52-62	SAFB like transcription modulator	Homo sapiens	14-17
31339066-5	2019	Results: Four MET mutations conferred resistance to crizotinib with sustained activation of downstream signaling pathways of MET.	Crizotinib	52-62	SAFB like transcription modulator	Homo sapiens	125-128
30890623-1	2019	Lorlatinib is a novel, highly potent, brain-penetrant, third-generation ALK/ROS1 tyrosine kinase inhibitor (TKI), which has broad-spectrum potency against most known resistance mutations that can develop during treatment with crizotinib and second-generation ALK TKIs.	Crizotinib	226-236	ALK receptor tyrosine kinase	Homo sapiens	72-75
30980071-0	2019	Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	14-18
31345828-2	2019	However, almost all patients will experience disease progression after front-line ALK-TKIs such as crizotinib.	Crizotinib	99-109	ALK receptor tyrosine kinase	Homo sapiens	82-85
31345828-7	2019	Lorlatinib can overcome ALK resistance to crizotinib, and the presented cases suggest a potential role for lorlatinib in patients with rapidly progressive cerebral and leptomeningeal metastases.	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	24-27
31380285-7	2019	Inhibition of ERBB1/2/4 using neratinib or of c-MET using crizotinib significantly enhanced [pazopanib + entinostat] lethality.	Crizotinib	58-68	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	46-51
31278140-3	2019	Crizotinib, a small molecule inhibitor of c-Met and ALK, is a Food and Drug Administration-approved drug with reported efficacy in the treatment of cancer.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	42-47
31278140-3	2019	Crizotinib, a small molecule inhibitor of c-Met and ALK, is a Food and Drug Administration-approved drug with reported efficacy in the treatment of cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	52-55
31278140-7	2019	In this study, we investigated the sensitivities of human TPM4 (hTPM4), human ALK (hALK), and their fusion gene (hTPM4-hALK) to crizotinib by measuring the lifespan of transgenic Drosophila Flies overexpressing hTPM4-hALK, hTPM4 and hALK showed decreased lifespans compared with controls.	Crizotinib	128-138	tropomyosin 4	Homo sapiens	58-62
31278140-7	2019	In this study, we investigated the sensitivities of human TPM4 (hTPM4), human ALK (hALK), and their fusion gene (hTPM4-hALK) to crizotinib by measuring the lifespan of transgenic Drosophila Flies overexpressing hTPM4-hALK, hTPM4 and hALK showed decreased lifespans compared with controls.	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	78-81
31278140-7	2019	In this study, we investigated the sensitivities of human TPM4 (hTPM4), human ALK (hALK), and their fusion gene (hTPM4-hALK) to crizotinib by measuring the lifespan of transgenic Drosophila Flies overexpressing hTPM4-hALK, hTPM4 and hALK showed decreased lifespans compared with controls.	Crizotinib	128-138	tropomyosin 4	Homo sapiens	113-118
31278140-7	2019	In this study, we investigated the sensitivities of human TPM4 (hTPM4), human ALK (hALK), and their fusion gene (hTPM4-hALK) to crizotinib by measuring the lifespan of transgenic Drosophila Flies overexpressing hTPM4-hALK, hTPM4 and hALK showed decreased lifespans compared with controls.	Crizotinib	128-138	tropomyosin 4	Homo sapiens	113-118
31278140-7	2019	In this study, we investigated the sensitivities of human TPM4 (hTPM4), human ALK (hALK), and their fusion gene (hTPM4-hALK) to crizotinib by measuring the lifespan of transgenic Drosophila Flies overexpressing hTPM4-hALK, hTPM4 and hALK showed decreased lifespans compared with controls.	Crizotinib	128-138	tropomyosin 4	Homo sapiens	113-118
31278140-8	2019	Although crizotinib is an inhibitor of ALK, treatment with crizotinib significantly extended the lifespans of Drosophila expressing hTPM4 and hTPM4-hALK but had no effect on hALK-expressing flies.	Crizotinib	9-19	Anaplastic lymphoma kinase	Drosophila melanogaster	39-42
31278140-8	2019	Although crizotinib is an inhibitor of ALK, treatment with crizotinib significantly extended the lifespans of Drosophila expressing hTPM4 and hTPM4-hALK but had no effect on hALK-expressing flies.	Crizotinib	59-69	tropomyosin 4	Homo sapiens	132-137
31278140-8	2019	Although crizotinib is an inhibitor of ALK, treatment with crizotinib significantly extended the lifespans of Drosophila expressing hTPM4 and hTPM4-hALK but had no effect on hALK-expressing flies.	Crizotinib	59-69	tropomyosin 4	Homo sapiens	142-147
31278140-10	2019	We confirmed that hTPM4-hALK was phosphorylated at Tyr1278 in a ligand-independent manner, and hTPM4-hALK-expressing flies treated with crizotinib showed a decreased level of Tyr1278 phosphorylation compared with untreated hTPM4-hALK-expressing flies, with a greater decrease induced by 1 microM compared with 200 nM crizotinib.	Crizotinib	136-146	tropomyosin 4	Homo sapiens	95-100
31278140-10	2019	We confirmed that hTPM4-hALK was phosphorylated at Tyr1278 in a ligand-independent manner, and hTPM4-hALK-expressing flies treated with crizotinib showed a decreased level of Tyr1278 phosphorylation compared with untreated hTPM4-hALK-expressing flies, with a greater decrease induced by 1 microM compared with 200 nM crizotinib.	Crizotinib	136-146	tropomyosin 4	Homo sapiens	95-100
31278140-10	2019	We confirmed that hTPM4-hALK was phosphorylated at Tyr1278 in a ligand-independent manner, and hTPM4-hALK-expressing flies treated with crizotinib showed a decreased level of Tyr1278 phosphorylation compared with untreated hTPM4-hALK-expressing flies, with a greater decrease induced by 1 microM compared with 200 nM crizotinib.	Crizotinib	317-327	tropomyosin 4	Homo sapiens	95-100
31278140-10	2019	We confirmed that hTPM4-hALK was phosphorylated at Tyr1278 in a ligand-independent manner, and hTPM4-hALK-expressing flies treated with crizotinib showed a decreased level of Tyr1278 phosphorylation compared with untreated hTPM4-hALK-expressing flies, with a greater decrease induced by 1 microM compared with 200 nM crizotinib.	Crizotinib	317-327	tropomyosin 4	Homo sapiens	95-100
31278140-11	2019	Taken together, the results suggest that crizotinib is effective for treating ALK-driven cancer and might be a new therapeutic drug, without cardiac or respiratory muscle toxic effects, for TPM4-expressing cancers.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	78-81
31278140-11	2019	Taken together, the results suggest that crizotinib is effective for treating ALK-driven cancer and might be a new therapeutic drug, without cardiac or respiratory muscle toxic effects, for TPM4-expressing cancers.	Crizotinib	41-51	tropomyosin 4	Homo sapiens	190-194
30980071-1	2019	BACKGROUND: In the ongoing phase I PROFILE 1001 study, crizotinib showed antitumor activity in patients with ROS1-rearranged advanced non-small-cell lung cancer (NSCLC).	Crizotinib	55-65	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	109-113
29925295-4	2019	In non-small cell lung cancer, it has been shown that about a third of patients who progress on the first generation ALK inhibitor, crizotinib develops mutations in the ALK kinase domain.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	117-120
31127319-2	2019	Crizotinib is a selective tyrosine kinase inhibitor of ALK, ROS1, and MET and a substrate of CYP3A.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	55-58
31127319-2	2019	Crizotinib is a selective tyrosine kinase inhibitor of ALK, ROS1, and MET and a substrate of CYP3A.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	60-64
31127319-2	2019	Crizotinib is a selective tyrosine kinase inhibitor of ALK, ROS1, and MET and a substrate of CYP3A.	Crizotinib	0-10	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	93-98
31127319-5	2019	Frequency and reasons for use of concomitant CYP3A inducers, including dexamethasone, with crizotinib were characterized.	Crizotinib	91-101	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	45-50
30679328-0	2019	Blockade of crizotinib-induced BCL2 elevation in ALK-positive anaplastic large cell lymphoma triggers autophagy associated with cell death.	Crizotinib	12-22	BCL2 apoptosis regulator	Homo sapiens	31-35
30679328-0	2019	Blockade of crizotinib-induced BCL2 elevation in ALK-positive anaplastic large cell lymphoma triggers autophagy associated with cell death.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	49-52
30679328-3	2019	We have previously shown that treatment of ALK-positive anaplastic large cell lymphoma cells with the ALK tyrosine kinase inhibitor crizotinib induces autophagy as a pro-survival response.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	43-46
30679328-3	2019	We have previously shown that treatment of ALK-positive anaplastic large cell lymphoma cells with the ALK tyrosine kinase inhibitor crizotinib induces autophagy as a pro-survival response.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	102-105
30679328-4	2019	Here, we observed that crizotinib-mediated inactivation of ALK caused an increase in BCL2 levels that restrained the cytotoxic effects of the drug.	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	59-62
30679328-4	2019	Here, we observed that crizotinib-mediated inactivation of ALK caused an increase in BCL2 levels that restrained the cytotoxic effects of the drug.	Crizotinib	23-33	BCL2 apoptosis regulator	Homo sapiens	85-89
30902613-12	2019	Investigator-assessed PFS was longer for alectinib than for crizotinib across EML4-ALK variants 1, 2, and 3a/b in plasma and tissue.	Crizotinib	60-70	EMAP like 4	Homo sapiens	78-82
30902613-12	2019	Investigator-assessed PFS was longer for alectinib than for crizotinib across EML4-ALK variants 1, 2, and 3a/b in plasma and tissue.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	83-86
30978502-3	2019	Here we present data on efficacy and safety of a prospective phase II trial evaluating crizotinib in European ROS1-positive patients (EUCROSS).	Crizotinib	87-97	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	110-114
31235037-0	2019	Responder of Gefitinib Plus Crizotinib in Osimertinib Failure EGFR-mutant NSCLC-Resistant With Newly Identified STRN-ALK by Next-Generation Sequencing.	Crizotinib	28-38	epidermal growth factor receptor	Homo sapiens	62-66
31235037-0	2019	Responder of Gefitinib Plus Crizotinib in Osimertinib Failure EGFR-mutant NSCLC-Resistant With Newly Identified STRN-ALK by Next-Generation Sequencing.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	117-120
31463126-0	2019	Efficacy and safety of crizotinib in patients with ROS1 rearranged non-small cell lung cancer: a retrospective analysis.	Crizotinib	23-33	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	51-55
31008509-0	2019	Treatment status and safety of crizotinib in 2028 Japanese patients with ALK-positive NSCLC in clinical settings.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	73-76
29925295-4	2019	In non-small cell lung cancer, it has been shown that about a third of patients who progress on the first generation ALK inhibitor, crizotinib develops mutations in the ALK kinase domain.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	169-172
30762593-0	2019	Case series of MET exon 14 skipping mutation-positive non-small-cell lung cancers with response to crizotinib and cabozantinib.	Crizotinib	99-109	SAFB like transcription modulator	Homo sapiens	15-18
31200813-1	2019	OBJECTIVES: Brigatinib is a second-generation ALK inhibitor which demonstrated activity over crizotinib-resistance, especially on brain metastasis by increased blood-brain penetration.	Crizotinib	93-103	ALK receptor tyrosine kinase	Homo sapiens	46-49
31499745-0	2019	Gastric cancer patient with c-MET amplification treated with crizotinib after failed multi-line treatment: A case report and literature review.	Crizotinib	61-71	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	28-33
31499745-6	2019	Crizotinib is a small molecule inhibitor against MET.	Crizotinib	0-10	SAFB like transcription modulator	Homo sapiens	49-52
31499745-7	2019	There are few reports of crizotinib in gastric cancer patients with c-MET amplification.	Crizotinib	25-35	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	68-73
31085007-1	2019	BACKGROUND: ROS1 rearrangement accounts for 1%-2% of non-small cell lung cancer (NSCLC) with a remarkable response to crizotinib.	Crizotinib	118-128	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	12-16
31354290-2	2019	There are currently several ALK inhibitors, including crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib which have been licensed by the US Food and Drug Administration or the European Medicines Agency for the treatment of ALK+ NSCLC patients.	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	28-31
31354290-2	2019	There are currently several ALK inhibitors, including crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib which have been licensed by the US Food and Drug Administration or the European Medicines Agency for the treatment of ALK+ NSCLC patients.	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	233-236
31354290-5	2019	It is additionally approved for ALK+ NSCLC previously treated with crizotinib.	Crizotinib	67-77	ALK receptor tyrosine kinase	Homo sapiens	32-35
30762593-2	2019	We report our institutional experience treating patients with MET exon 14 skipping (METex14) mutations, including responses to the MET inhibitors crizotinib and cabozantinib.	Crizotinib	146-156	SAFB like transcription modulator	Homo sapiens	62-65
30762593-2	2019	We report our institutional experience treating patients with MET exon 14 skipping (METex14) mutations, including responses to the MET inhibitors crizotinib and cabozantinib.	Crizotinib	146-156	SAFB like transcription modulator	Homo sapiens	84-87
30863883-0	2019	Short-time use of crizotinib as neoadjuvant in ALK-positive non-small cell lung carcinoma can be a chance for resectability.	Crizotinib	18-28	ALK receptor tyrosine kinase	Homo sapiens	47-50
30863883-1	2019	Because of the rapid response to crizotinib, patients with ALK-positive locally advanced disease may become resectable with the use of neoadjuvant crizotinib.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	59-62
30863883-1	2019	Because of the rapid response to crizotinib, patients with ALK-positive locally advanced disease may become resectable with the use of neoadjuvant crizotinib.	Crizotinib	147-157	ALK receptor tyrosine kinase	Homo sapiens	59-62
31354217-0	2019	Impact of crizotinib on long-term survival of ALK-positive advanced non-small-cell lung cancer: A Chinese multicenter cohort study.	Crizotinib	10-20	ALK receptor tyrosine kinase	Homo sapiens	46-49
31354217-1	2019	Objective: Crizotinib has demonstrated promising efficacy in patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) in clinical trials.	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	75-101
31354217-1	2019	Objective: Crizotinib has demonstrated promising efficacy in patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) in clinical trials.	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	103-106
31354217-2	2019	We conducted this retrospective multicenter study to assess the outcomes of crizotinib therapy in, to our knowledge, a large sample cohort of patients with ALK-positive advanced NSCLC.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	156-159
31354217-10	2019	Conclusions: This study has demonstrated the clinically meaningful benefit of crizotinib treatment in a large cohort of Chinese ALK-positive NSCLC patients.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	128-131
31354217-11	2019	CBPD and next-generation ALK inhibitor treatment may provide improved survival after RECIST-defined progression on crizotinib.	Crizotinib	115-125	ALK receptor tyrosine kinase	Homo sapiens	25-28
31098955-7	2019	Induced expression of EML4-ALK in A549 cells significantly increased PD-L1 protein expression, whereas PD-L1 protein expression was downregulated after crizotinib and pembrolizumab successively.	Crizotinib	152-162	EMAP like 4	Homo sapiens	22-26
31098955-7	2019	Induced expression of EML4-ALK in A549 cells significantly increased PD-L1 protein expression, whereas PD-L1 protein expression was downregulated after crizotinib and pembrolizumab successively.	Crizotinib	152-162	ALK receptor tyrosine kinase	Homo sapiens	27-30
31098955-7	2019	Induced expression of EML4-ALK in A549 cells significantly increased PD-L1 protein expression, whereas PD-L1 protein expression was downregulated after crizotinib and pembrolizumab successively.	Crizotinib	152-162	CD274 molecule	Homo sapiens	103-108
31098955-9	2019	PD-L1 overexpression was significantly associated with shorter progressive survival and overall survival after crizotinib in ALK-translocated patients.	Crizotinib	111-121	CD274 molecule	Homo sapiens	0-5
31098955-9	2019	PD-L1 overexpression was significantly associated with shorter progressive survival and overall survival after crizotinib in ALK-translocated patients.	Crizotinib	111-121	ALK receptor tyrosine kinase	Homo sapiens	125-128
30822515-0	2019	Renal Effects of Crizotinib in Patients With ALK-Positive Advanced NSCLC.	Crizotinib	17-27	ALK receptor tyrosine kinase	Homo sapiens	45-48
31122560-0	2019	Identification of a Novel EML4-ALK, BCL11A-ALK Double-Fusion Variant in Lung Adenocarcinoma Using Next-Generation Sequencing and Response to Crizotinib.	Crizotinib	141-151	EMAP like 4	Homo sapiens	26-30
31122560-0	2019	Identification of a Novel EML4-ALK, BCL11A-ALK Double-Fusion Variant in Lung Adenocarcinoma Using Next-Generation Sequencing and Response to Crizotinib.	Crizotinib	141-151	ALK receptor tyrosine kinase	Homo sapiens	31-34
31122560-0	2019	Identification of a Novel EML4-ALK, BCL11A-ALK Double-Fusion Variant in Lung Adenocarcinoma Using Next-Generation Sequencing and Response to Crizotinib.	Crizotinib	141-151	BAF chromatin remodeling complex subunit BCL11A	Homo sapiens	36-42
31122560-0	2019	Identification of a Novel EML4-ALK, BCL11A-ALK Double-Fusion Variant in Lung Adenocarcinoma Using Next-Generation Sequencing and Response to Crizotinib.	Crizotinib	141-151	ALK receptor tyrosine kinase	Homo sapiens	43-46
31122565-0	2019	A Novel CAV1-MET Fusion in SCLC Transformation Responds to Crizotinib and Osimertinib Treatment.	Crizotinib	59-69	caveolin 1	Homo sapiens	8-12
31122565-0	2019	A Novel CAV1-MET Fusion in SCLC Transformation Responds to Crizotinib and Osimertinib Treatment.	Crizotinib	59-69	SAFB like transcription modulator	Homo sapiens	13-16
30976989-2	2019	Crizotinib, an oral small-molecule tyrosine kinase inhibitor (TKI) that targets anaplastic lymphoma kinase (ALK), MET, and ROS1, has shown marked antitumor activity in patients with ROS1-positive advanced NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	80-106
30976989-2	2019	Crizotinib, an oral small-molecule tyrosine kinase inhibitor (TKI) that targets anaplastic lymphoma kinase (ALK), MET, and ROS1, has shown marked antitumor activity in patients with ROS1-positive advanced NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	108-111
30976989-2	2019	Crizotinib, an oral small-molecule tyrosine kinase inhibitor (TKI) that targets anaplastic lymphoma kinase (ALK), MET, and ROS1, has shown marked antitumor activity in patients with ROS1-positive advanced NSCLC.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	123-127
30976989-2	2019	Crizotinib, an oral small-molecule tyrosine kinase inhibitor (TKI) that targets anaplastic lymphoma kinase (ALK), MET, and ROS1, has shown marked antitumor activity in patients with ROS1-positive advanced NSCLC.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	182-186
30976989-3	2019	OBJECTIVE: Our objective was to analyze the efficacy and safety of crizotinib treatment in Chinese patients with advanced NSCLC with ROS1 rearrangement in real-world clinical practice.	Crizotinib	67-77	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	133-137
30976989-14	2019	CONCLUSION: Crizotinib was effective and well tolerated in Chinese patients with ROS1-positive advanced NSCLC in real-world clinical practice.	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	81-85
31025247-0	2019	Efficacy of Crizotinib for Advanced ALK-Rearranged Non-Small-Cell Lung Cancer Patients with Brain Metastasis: A Multicenter, Retrospective Study in China.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	36-39
30863883-6	2019	Short-term neoadjuvant therapy with crizotinib for 4 weeks might be a promising therapy in locally advanced ALK-positive NSCLC and might provide a chance for resectability.	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	108-111
31025247-1	2019	BACKGROUND: The efficacy of crizotinib for anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) patients with brain metastasis is controversial.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	43-69
31025247-1	2019	BACKGROUND: The efficacy of crizotinib for anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) patients with brain metastasis is controversial.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	71-74
31025247-4	2019	PATIENTS AND METHODS: We reviewed the medical records of unselected ALK-rearranged NSCLC patients treated with crizotinib at five hospitals in China from January 1, 2013 to November 30, 2017.	Crizotinib	111-121	ALK receptor tyrosine kinase	Homo sapiens	68-71
31025247-11	2019	CONCLUSIONS: ALK-rearranged advanced NSCLC patients with baseline brain metastasis can still achieve OS benefits from crizotinib treatment.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	13-16
31191129-2	2019	Lung adenocarcinomas harboring ALK translocations may be targeted with drugs such as crizotinib.	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	31-34
30638795-0	2019	Combined Use of Crizotinib and Gefitinib in Advanced Lung Adenocarcinoma With Leptomeningeal Metastases Harboring MET Amplification After the Development of Gefitinib Resistance: A Case Report and Literature Review.	Crizotinib	16-26	SAFB like transcription modulator	Homo sapiens	114-117
31280674-4	2019	Interestingly, all of the target compounds displayed IC50 values in the range of 3.9-11.1 nM in the c-Met kinase inhibition assay which were lower than the value for crizotinib (11.1 nM).	Crizotinib	166-176	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	100-105
31280674-5	2019	Conclusion: Target compound 10b can be considered as a leading drug candidate due to its lower IC50 values than crizotinib in both HGF-induced proliferation and c-Met kinase inhibition assays.	Crizotinib	112-122	hepatocyte growth factor	Homo sapiens	131-134
31280674-5	2019	Conclusion: Target compound 10b can be considered as a leading drug candidate due to its lower IC50 values than crizotinib in both HGF-induced proliferation and c-Met kinase inhibition assays.	Crizotinib	112-122	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	161-166
31027745-0	2019	Next-Generation Sequencer Analysis of Pulmonary Pleomorphic Carcinoma With a CD74-ROS1 Fusion Successfully Treated With Crizotinib.	Crizotinib	120-130	CD74 molecule	Homo sapiens	77-81
31027745-0	2019	Next-Generation Sequencer Analysis of Pulmonary Pleomorphic Carcinoma With a CD74-ROS1 Fusion Successfully Treated With Crizotinib.	Crizotinib	120-130	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	82-86
31027700-0	2019	Comparison of ALK detection by FISH, IHC and NGS to predict benefit from crizotinib in advanced non-small-cell lung cancer.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	14-17
31118681-5	2019	The efficacy of crizotinib treatment was evaluated in ROS1 fusion-positive NSCLC patients.	Crizotinib	16-26	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	54-58
30920172-0	2019	Favorable predictors for survival in advanced ALK-positive non-small cell lung cancer patients beyond crizotinib resistance.	Crizotinib	102-112	ALK receptor tyrosine kinase	Homo sapiens	46-49
30920172-1	2019	BACKGROUND: Crizotinib has demonstrated favorable efficacy in patients with advanced ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	85-88
30920172-2	2019	Unfortunately, the majority of ALK-positive patients ultimately develop acquired resistance within one year after the initiation of crizotinib treatment; however, the estimation of overall survival (OS) beyond crizotinib resistance has not yet been fully demonstrated.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	31-34
30920172-2	2019	Unfortunately, the majority of ALK-positive patients ultimately develop acquired resistance within one year after the initiation of crizotinib treatment; however, the estimation of overall survival (OS) beyond crizotinib resistance has not yet been fully demonstrated.	Crizotinib	210-220	ALK receptor tyrosine kinase	Homo sapiens	31-34
30920172-12	2019	CONCLUSION: Long PFS with crizotinib (>=10.4 months), intracranial progression, and use of next-generation ALK inhibitors might be favorable predictors for OS in advanced ALK-positive NSCLC patients.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	174-177
30993895-0	2019	Clinical features and outcomes of ALK rearranged non-small cell lung cancer with primary resistance to crizotinib.	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	34-37
30993895-1	2019	BACKGROUND: Crizotinib is associated with a favorable survival benefit in patients with ALK-positive non-small cell lung cancer (NSCLC); however, a subset of patients harboring ALK rearrangement shows a poor response.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	88-91
30993895-1	2019	BACKGROUND: Crizotinib is associated with a favorable survival benefit in patients with ALK-positive non-small cell lung cancer (NSCLC); however, a subset of patients harboring ALK rearrangement shows a poor response.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	177-180
30993895-7	2019	Patients administered ALK-tyrosine kinase inhibitors after crizotinib progression had significantly longer survival than the PRR group treated with best supportive care (P = 0.007), but no significant difference was found between ALK-tyrosine kinase inhibitor treatment and single chemotherapy (P = 0.944).	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	22-25
30993895-9	2019	Nevertheless, next-generation ALK inhibitors and chemotherapy after crizotinib progression could confer a therapeutic and survival benefit in this population.	Crizotinib	68-78	ALK receptor tyrosine kinase	Homo sapiens	30-33
30742941-2	2019	In this study, we investigated the therapeutic combination of a CD30-targeting ADC (anti-CD30-lidamycin [LDM]) with a small-molecule inhibitor (crizotinib) of nucleophosmin-anaplastic lymphoma kinase NPM-ALK in CD30+/ALK+ anaplastic large cell lymphoma (ALCL).	Crizotinib	144-154	ALK receptor tyrosine kinase	Homo sapiens	204-207
30742941-2	2019	In this study, we investigated the therapeutic combination of a CD30-targeting ADC (anti-CD30-lidamycin [LDM]) with a small-molecule inhibitor (crizotinib) of nucleophosmin-anaplastic lymphoma kinase NPM-ALK in CD30+/ALK+ anaplastic large cell lymphoma (ALCL).	Crizotinib	144-154	ALK receptor tyrosine kinase	Homo sapiens	217-220
30742941-3	2019	In vitro, anti-CD30-LDM showed strong synergistic antiproliferative activity when combined with crizotinib.	Crizotinib	96-106	TNF receptor superfamily member 8	Homo sapiens	15-19
30742941-6	2019	Interestingly, the addition of crizotinib inhibited the expression of phosphorylated ERK1/2 and further augmented anti-CD30-LDM-mediated apoptosis, providing a potential synergistic mechanism for DNA-damaging agents combined with NPM-ALK inhibitors.	Crizotinib	31-41	mitogen-activated protein kinase 3	Homo sapiens	85-91
30742941-6	2019	Interestingly, the addition of crizotinib inhibited the expression of phosphorylated ERK1/2 and further augmented anti-CD30-LDM-mediated apoptosis, providing a potential synergistic mechanism for DNA-damaging agents combined with NPM-ALK inhibitors.	Crizotinib	31-41	TNF receptor superfamily member 8	Homo sapiens	119-123
30742941-6	2019	Interestingly, the addition of crizotinib inhibited the expression of phosphorylated ERK1/2 and further augmented anti-CD30-LDM-mediated apoptosis, providing a potential synergistic mechanism for DNA-damaging agents combined with NPM-ALK inhibitors.	Crizotinib	31-41	nucleophosmin 1	Homo sapiens	230-233
30742941-6	2019	Interestingly, the addition of crizotinib inhibited the expression of phosphorylated ERK1/2 and further augmented anti-CD30-LDM-mediated apoptosis, providing a potential synergistic mechanism for DNA-damaging agents combined with NPM-ALK inhibitors.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	234-237
30742941-8	2019	This research demonstrated for the first time that the combination of anti-CD30-LDM and crizotinib exhibits a synergistic inhibitory effect in tumor cells.	Crizotinib	88-98	TNF receptor superfamily member 8	Homo sapiens	75-79
31114237-5	2019	Since the biopsy was ALK (D5F3) positive, the effect of crizotinib treatment was significant, though crizotinib resistance unfortunately only occurred after 4 months.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	21-24
31143519-1	2019	Crizotinib is a tyrosine kinase inhibitor (TKI) approved for the treatment of non-small cell lung cancers (NSLCL) and lymphomas expressing activating translocations or mutations of oncogenic tyrosine kinases (in particular ALK and ROS1).	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	223-226
31143519-1	2019	Crizotinib is a tyrosine kinase inhibitor (TKI) approved for the treatment of non-small cell lung cancers (NSLCL) and lymphomas expressing activating translocations or mutations of oncogenic tyrosine kinases (in particular ALK and ROS1).	Crizotinib	0-10	Ros1 proto-oncogene	Mus musculus	231-235
31143519-2	2019	We recently observed that high-dose (final concentration in vivo: ~10 microM) crizotinib can induce immunogenic cell death (ICD) in cancer cells lacking ALK/ROS1 activation through off-target effects that require the inhibition of several other tyrosine kinases.	Crizotinib	78-88	anaplastic lymphoma kinase	Mus musculus	153-156
31143519-2	2019	We recently observed that high-dose (final concentration in vivo: ~10 microM) crizotinib can induce immunogenic cell death (ICD) in cancer cells lacking ALK/ROS1 activation through off-target effects that require the inhibition of several other tyrosine kinases.	Crizotinib	78-88	Ros1 proto-oncogene	Mus musculus	157-161
30791979-0	2019	miR-100-5p confers resistance to ALK tyrosine kinase inhibitors Crizotinib and Lorlatinib in EML4-ALK positive NSCLC.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	33-36
30791979-0	2019	miR-100-5p confers resistance to ALK tyrosine kinase inhibitors Crizotinib and Lorlatinib in EML4-ALK positive NSCLC.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	98-101
30791979-9	2019	Furthermore, ALK TKI-refractory cancer cells were exposed to a synthetic miRNA inhibitory Locked Nucleic Acid (LNA)-library in the presence of ALK TKIs Crizotinib or Lorlatinib.	Crizotinib	152-162	ALK receptor tyrosine kinase	Homo sapiens	13-16
30791979-10	2019	The outcome of the combined approaches uncovered miR-100-5p to confer resistance to Crizotinib and Lorlatinib in EML4-ALK NSCLC cells and to be a potential therapeutic target in drug resistance.	Crizotinib	84-94	EMAP like 4	Homo sapiens	113-117
30791979-10	2019	The outcome of the combined approaches uncovered miR-100-5p to confer resistance to Crizotinib and Lorlatinib in EML4-ALK NSCLC cells and to be a potential therapeutic target in drug resistance.	Crizotinib	84-94	ALK receptor tyrosine kinase	Homo sapiens	118-121
30940805-5	2019	Crizotinib plus cisplatin leads to an increase in the expression of PD-1 and PD-L1 in tumors, coupled to a strong sensitization of NSCLC to immunotherapy with PD-1 antibodies.	Crizotinib	0-10	programmed cell death 1	Homo sapiens	68-72
30940805-5	2019	Crizotinib plus cisplatin leads to an increase in the expression of PD-1 and PD-L1 in tumors, coupled to a strong sensitization of NSCLC to immunotherapy with PD-1 antibodies.	Crizotinib	0-10	programmed cell death 1	Homo sapiens	159-163
30737231-3	2019	In this study, we report that both ALK-mutant L1196M and EMT were concomitantly detected in a single crizotinib-resistant lesion in a patient with ALK-rearranged lung cancer.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	35-38
30737231-3	2019	In this study, we report that both ALK-mutant L1196M and EMT were concomitantly detected in a single crizotinib-resistant lesion in a patient with ALK-rearranged lung cancer.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	147-150
30737231-5	2019	Preclinical experiments with crizotinib-resistant lung cancer cells showed that EMT associated with decreased expression of miR-200c and increased expression of ZEB1 caused cross-resistance to new-generation ALK inhibitors alectinib, ceritinib, and lorlatinib.	Crizotinib	29-39	microRNA 200c	Homo sapiens	124-132
30737231-5	2019	Preclinical experiments with crizotinib-resistant lung cancer cells showed that EMT associated with decreased expression of miR-200c and increased expression of ZEB1 caused cross-resistance to new-generation ALK inhibitors alectinib, ceritinib, and lorlatinib.	Crizotinib	29-39	zinc finger E-box binding homeobox 1	Homo sapiens	161-165
30737231-5	2019	Preclinical experiments with crizotinib-resistant lung cancer cells showed that EMT associated with decreased expression of miR-200c and increased expression of ZEB1 caused cross-resistance to new-generation ALK inhibitors alectinib, ceritinib, and lorlatinib.	Crizotinib	29-39	ALK receptor tyrosine kinase	Homo sapiens	208-211
30737231-8	2019	SIGNIFICANCE: These findings show that dual inhibition of HDAC and ALK receptor tyrosine kinase activities provides a means to circumvent crizotinib resistance in lung cancer.	Crizotinib	138-148	ALK receptor tyrosine kinase	Homo sapiens	67-70
30843662-0	2019	Concomitant TP53 mutations with response to crizotinib treatment in patients with ALK-rearranged non-small-cell lung cancer.	Crizotinib	44-54	tumor protein p53	Homo sapiens	12-16
30843662-0	2019	Concomitant TP53 mutations with response to crizotinib treatment in patients with ALK-rearranged non-small-cell lung cancer.	Crizotinib	44-54	ALK receptor tyrosine kinase	Homo sapiens	82-85
30843662-4	2019	The clinicopathologic features of the TP53 mutations and its impact on the effect of crizotinib treatment were analyzed.	Crizotinib	85-95	tumor protein p53	Homo sapiens	38-42
30843662-11	2019	CONCLUSIONS: TP53 mutations, especially nondisruptive mutations, negatively affected the response to crizotinib and correlated with shorter PFS in ALK-rearranged NSCLC patients.	Crizotinib	101-111	tumor protein p53	Homo sapiens	13-17
30843662-11	2019	CONCLUSIONS: TP53 mutations, especially nondisruptive mutations, negatively affected the response to crizotinib and correlated with shorter PFS in ALK-rearranged NSCLC patients.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	147-150
31156305-0	2019	Sequential therapy according to distinct disease progression patterns in advanced ALK-positive non-small-cell lung cancer after crizotinib treatment.	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	82-85
31156305-1	2019	Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC).	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	76-102
31156305-1	2019	Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC).	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	104-107
30879923-0	2019	Cyclosporine A sensitizes lung cancer cells to crizotinib through inhibition of the Ca2+/calcineurin/Erk pathway.	Crizotinib	47-57	mitogen-activated protein kinase 1	Homo sapiens	101-104
30879923-9	2019	Mechanistically, crizotinib treatment led to the activation of Ca2+-calcineurin (CaN)-Kinase suppressor of Ras 2 (KSR2) signaling, resulting in Erk1/2 activation and enhanced survival of cancer cells.	Crizotinib	17-27	kinase suppressor of ras 2	Homo sapiens	86-112
30879923-9	2019	Mechanistically, crizotinib treatment led to the activation of Ca2+-calcineurin (CaN)-Kinase suppressor of Ras 2 (KSR2) signaling, resulting in Erk1/2 activation and enhanced survival of cancer cells.	Crizotinib	17-27	kinase suppressor of ras 2	Homo sapiens	114-118
30879923-9	2019	Mechanistically, crizotinib treatment led to the activation of Ca2+-calcineurin (CaN)-Kinase suppressor of Ras 2 (KSR2) signaling, resulting in Erk1/2 activation and enhanced survival of cancer cells.	Crizotinib	17-27	mitogen-activated protein kinase 3	Homo sapiens	144-150
30879923-10	2019	CsA effectively blocked CaN-KSR2-Erk1/2 signaling, promoting crizotinib-induced apoptosis and G2/M arrest.	Crizotinib	61-71	kinase suppressor of ras 2	Homo sapiens	28-32
30879923-11	2019	Similarly, pharmacologic or genetic inhibition of Erk1/2 also enhanced crizotinib-induced growth inhibition in vitro.	Crizotinib	71-81	mitogen-activated protein kinase 3	Homo sapiens	50-56
30879923-12	2019	Xenograft studies further confirmed that CsA or Erk1/2 inhibitor PD98059 enhanced the anti-cancer activity of crizotinib through inhibition of CaN-Erk1/2 axis.	Crizotinib	110-120	mitogen-activated protein kinase 3	Homo sapiens	48-54
30879923-12	2019	Xenograft studies further confirmed that CsA or Erk1/2 inhibitor PD98059 enhanced the anti-cancer activity of crizotinib through inhibition of CaN-Erk1/2 axis.	Crizotinib	110-120	mitogen-activated protein kinase 3	Homo sapiens	147-153
30652510-0	2019	Comparison of cardiovascular effects of crizotinib and chemotherapy in ALK-positive advanced non-small-cell lung cancer.	Crizotinib	40-50	ALK receptor tyrosine kinase	Homo sapiens	71-74
30066208-4	2019	Here we report the case of a stage IV ALK-rearranged NSCLC patient exposed to serial crizotinib, brigatinib, ceritinib, and lorlatinib (this latter brought to complete brain and leptomeningeal disease response), in a period of more than five years.	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	38-41
30449794-0	2019	Effectiveness of Crizotinib for Inflammatory Myofibroblastic Tumor with ALK mutation.	Crizotinib	17-27	ALK receptor tyrosine kinase	Homo sapiens	72-75
30449794-3	2019	While crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is only approved for non-small-cell lung cancer with ALK mutation, it is reportedly effective for other malignant tumors with ALK mutation.	Crizotinib	6-16	ALK receptor tyrosine kinase	Homo sapiens	21-47
30449794-3	2019	While crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is only approved for non-small-cell lung cancer with ALK mutation, it is reportedly effective for other malignant tumors with ALK mutation.	Crizotinib	6-16	ALK receptor tyrosine kinase	Homo sapiens	49-52
30449794-3	2019	While crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is only approved for non-small-cell lung cancer with ALK mutation, it is reportedly effective for other malignant tumors with ALK mutation.	Crizotinib	6-16	ALK receptor tyrosine kinase	Homo sapiens	118-121
30449794-3	2019	While crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is only approved for non-small-cell lung cancer with ALK mutation, it is reportedly effective for other malignant tumors with ALK mutation.	Crizotinib	6-16	ALK receptor tyrosine kinase	Homo sapiens	118-121
30449794-4	2019	We herein report a case involving a 37-year-old woman with retroperitoneal IMT with ALK mutation, who experienced recurrence after complete resection, in whom crizotinib treatment resulted in complete response.	Crizotinib	159-169	ALK receptor tyrosine kinase	Homo sapiens	84-87
30922571-0	2019	Neoadjuvant Crizotinib for ALK Re-arranged NSCLC?	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	27-30
30922580-0	2019	Identification of a Novel MET Exon 14 Skipping Variant Coexistent with EGFR Mutation in Lung Adenocarcinoma Sensitive to Combined Treatment with Afatinib and Crizotinib.	Crizotinib	158-168	epidermal growth factor receptor	Homo sapiens	71-75
30885356-10	2019	After an extensive discussion of treatment options, the patient opted to treatment with crizotinib, a small-molecule dual inhibitor of the MET and ALK.	Crizotinib	88-98	ALK receptor tyrosine kinase	Homo sapiens	147-150
30679319-5	2019	The tumor did respond to crizotinib, a first-generation ALK inhibitor.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	56-59
30679319-6	2019	When her tumor progressed, circulating tumor DNA detection revealed ALK L1196 M and G1269A mutation resistance to crizotinib, but she had a response to brigatinib.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	68-71
30888598-2	2019	The efficacy of EGFR tyrosine kinase inhibitors (TKIs) and the ALK-specific TKI crizotinib in these patients has not been well-established.	Crizotinib	80-90	ALK receptor tyrosine kinase	Homo sapiens	63-66
30888598-9	2019	The ORR to crizotinib was 66.7% (8/12) for double-positive patients and 65.0% (39/60) for ALK-rearranged patients (p = 1.00), with a median PFS of 11.1 and 12.5 months, respectively (HR 1.39; 95% CI 0.69-2.80; p = 0.28).	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	90-93
30981578-3	2019	Here we found that crizotinib showed good inhibitory activity against JAK2 by enzymatic assays (IC50 = 27 nM).	Crizotinib	19-29	Janus kinase 2	Homo sapiens	70-74
31213843-0	2019	Complete response to crizotinib in a metastatic adenocarcinoma of unknown primary harboring MET amplification and NTRK1 co-occurring mutation.	Crizotinib	21-31	neurotrophic receptor tyrosine kinase 1	Homo sapiens	114-119
32914017-0	2019	Crizotinib and Surgery for Long-Term Disease Control in Children and Adolescents With ALK-Positive Inflammatory Myofibroblastic Tumors.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	86-89
30626830-3	2019	We herein report the efficacy of crizotinib treatment for treating the symptoms of HPO associated with c-ros oncogene 1 receptor tyrosine kinase (ROS1)-rearranged lung cancer.	Crizotinib	33-43	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	103-144
30626830-3	2019	We herein report the efficacy of crizotinib treatment for treating the symptoms of HPO associated with c-ros oncogene 1 receptor tyrosine kinase (ROS1)-rearranged lung cancer.	Crizotinib	33-43	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	146-150
31190983-2	2019	At present, three or more generations of ALK inhibitors have been used for ALK-positive NSCLC treatment, including crizotinib, alectinib, ceritinib, and brigatinib.	Crizotinib	115-125	ALK receptor tyrosine kinase	Homo sapiens	41-44
30691963-0	2019	Durable Clinical Response to Crizotinib in IRF2BP2-NTRK1 Non-small-cell Lung Cancer.	Crizotinib	29-39	interferon regulatory factor 2 binding protein 2	Homo sapiens	43-50
30691963-0	2019	Durable Clinical Response to Crizotinib in IRF2BP2-NTRK1 Non-small-cell Lung Cancer.	Crizotinib	29-39	neurotrophic receptor tyrosine kinase 1	Homo sapiens	51-56
30819904-0	2019	Leukemic presentation of ALK-positive anaplastic large cell lymphoma with a novel partner, poly(A) binding protein cytoplasmic 1 (PABPC1), responding to single-agent crizotinib.	Crizotinib	166-176	ALK receptor tyrosine kinase	Homo sapiens	25-28
30819904-0	2019	Leukemic presentation of ALK-positive anaplastic large cell lymphoma with a novel partner, poly(A) binding protein cytoplasmic 1 (PABPC1), responding to single-agent crizotinib.	Crizotinib	166-176	poly(A) binding protein cytoplasmic 1	Homo sapiens	91-128
30819904-0	2019	Leukemic presentation of ALK-positive anaplastic large cell lymphoma with a novel partner, poly(A) binding protein cytoplasmic 1 (PABPC1), responding to single-agent crizotinib.	Crizotinib	166-176	poly(A) binding protein cytoplasmic 1	Homo sapiens	130-136
31095455-2	2019	The aim of this prospective-retrospective cohort study was to obtain real-world data on the use of crizotinib or chemotherapy in patients with ALK-positive metastatic NSCLC in Russia.	Crizotinib	99-109	ALK receptor tyrosine kinase	Homo sapiens	143-146
31095455-15	2019	CONCLUSION: The improved OS observed in crizotinib clinical trials in ALK-positive NSCLC was also observed in the less selective patient populations treated in daily practice in Russia.	Crizotinib	40-50	ALK receptor tyrosine kinase	Homo sapiens	70-73
30664990-5	2019	In addition, we used the Guardant360 NGS assay to detect potential genetic mediators of resistance in plasma from patients with ROS1-positive NSCLC who were relapsing on crizotinib.	Crizotinib	170-180	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	128-132
30664990-10	2019	Six (33%) of 18 post-crizotinib plasma specimens harbored ROS1 kinase domain mutations, five of which were ROS1 G2032R.	Crizotinib	21-31	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	58-62
30664990-10	2019	Six (33%) of 18 post-crizotinib plasma specimens harbored ROS1 kinase domain mutations, five of which were ROS1 G2032R.	Crizotinib	21-31	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	107-111
30664990-11	2019	Two (11%) post-crizotinib plasma specimens had genetic alterations (n = 1 each BRAF V600E and PIK3CA E545K) potentially associated with ROS1-independent signaling.	Crizotinib	15-25	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	136-140
30697903-3	2019	When standard surgical treatment is not feasible, ALK inhibitors may play an important role, as recently reported for the first-generation ALK inhibitors (crizotinib).	Crizotinib	155-165	ALK receptor tyrosine kinase	Homo sapiens	50-53
30697903-3	2019	When standard surgical treatment is not feasible, ALK inhibitors may play an important role, as recently reported for the first-generation ALK inhibitors (crizotinib).	Crizotinib	155-165	ALK receptor tyrosine kinase	Homo sapiens	139-142
30298279-7	2019	The evidence selected in support of crizotinib was PROFILE 1014, an open-label RCT of crizotinib, compared with pemetrexed/cisplatin CT (without maintenance therapy), in previously untreated advanced or metastatic ALK+ NSCLC.	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	214-217
30742941-0	2019	Crizotinib enhances anti-CD30-LDM induced antitumor efficacy in NPM-ALK positive anaplastic large cell lymphoma.	Crizotinib	0-10	TNF receptor superfamily member 8	Homo sapiens	25-29
30742941-0	2019	Crizotinib enhances anti-CD30-LDM induced antitumor efficacy in NPM-ALK positive anaplastic large cell lymphoma.	Crizotinib	0-10	nucleophosmin 1	Homo sapiens	64-67
30742941-0	2019	Crizotinib enhances anti-CD30-LDM induced antitumor efficacy in NPM-ALK positive anaplastic large cell lymphoma.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	68-71
30742941-2	2019	In this study, we investigated the therapeutic combination of a CD30-targeting ADC (anti-CD30-lidamycin [LDM]) with a small-molecule inhibitor (crizotinib) of nucleophosmin-anaplastic lymphoma kinase NPM-ALK in CD30+/ALK+ anaplastic large cell lymphoma (ALCL).	Crizotinib	144-154	nucleophosmin 1	Homo sapiens	200-203
30408570-0	2019	Neoadjuvant Crizotinib in Resectable Locally Advanced Non-Small Cell Lung Cancer with ALK Rearrangement.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	86-89
30408570-4	2019	METHODS: We have described 11 ALK receptor tyrosine kinase gene (ALK)-positive patients with pathologically confirmed N2 NSCLC who were treated with neoadjuvant crizotinib.	Crizotinib	161-171	ALK receptor tyrosine kinase	Homo sapiens	30-33
30408570-4	2019	METHODS: We have described 11 ALK receptor tyrosine kinase gene (ALK)-positive patients with pathologically confirmed N2 NSCLC who were treated with neoadjuvant crizotinib.	Crizotinib	161-171	ALK receptor tyrosine kinase	Homo sapiens	65-68
30521972-0	2019	Interstitial Lung Disease Onset and Its Risk Factors in Japanese Patients With ALK-Positive NSCLC After Treatment With Crizotinib.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	79-82
30888598-12	2019	CONCLUSIONS: Both first-generation EGFR TKIs and the ALK TKI crizotinib were effective in these patients.	Crizotinib	61-71	ALK receptor tyrosine kinase	Homo sapiens	53-56
30895431-0	2019	Distribution of ALK Fusion Variants and Correlation with Clinical Outcomes in Chinese Patients with Non-Small Cell Lung Cancer Treated with Crizotinib.	Crizotinib	140-150	ALK receptor tyrosine kinase	Homo sapiens	16-19
30895431-2	2019	Crizotinib, a US Food and Drug Administration (FDA)-approved tyrosine kinase inhibitor for treating ALK-rearranged NSCLC, has shown remarkable response in ALK-positive NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	100-103
30895431-2	2019	Crizotinib, a US Food and Drug Administration (FDA)-approved tyrosine kinase inhibitor for treating ALK-rearranged NSCLC, has shown remarkable response in ALK-positive NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	155-158
30895431-7	2019	The clinical response to crizotinib and survival data in ALK-positive patients was retrospectively analyzed.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	57-60
30895431-14	2019	CONCLUSIONS: This study illustrates the patterns of ALK fusion variants present in Chinese NSCLC patients and might help explain heterogeneous clinical outcomes to crizotinib treatment according to different ALK fusion variants.	Crizotinib	164-174	ALK receptor tyrosine kinase	Homo sapiens	52-55
30895431-14	2019	CONCLUSIONS: This study illustrates the patterns of ALK fusion variants present in Chinese NSCLC patients and might help explain heterogeneous clinical outcomes to crizotinib treatment according to different ALK fusion variants.	Crizotinib	164-174	ALK receptor tyrosine kinase	Homo sapiens	208-211
30866974-1	2019	BACKGROUND: Despite development of several next-generation tyrosine kinase inhibitors (TKIs), crizotinib remains one of the first-line treatment options for advanced ALK-positive NSCLC and is widely used in situations where next-generation TKIs aren"t yet approved or economically inaccessible.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	166-169
30866974-2	2019	However, the pattern of failure and clinical value of radiotherapy in metastatic crizotinib-treated ALK-mutant lung cancer, with or without baseline brain metastases (BBM), are largely unknown.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	100-103
30296185-12	2019	CONCLUSIONS: Despite widespread crizotinib use in patients with ALK+ aNSCLC, a high proportion of patients progressed.	Crizotinib	32-42	ALK receptor tyrosine kinase	Homo sapiens	64-67
30881166-0	2019	Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification.	Crizotinib	68-78	epidermal growth factor receptor	Homo sapiens	97-101
30657349-2	2019	The treatment drugs of ALK-positive NSCLC mainly included crizotinib, ceritinib, alectinib, and brigatinib.	Crizotinib	58-68	ALK receptor tyrosine kinase	Homo sapiens	23-26
30797494-0	2019	Mutation tracking of a patient with EGFR-mutant lung cancer harboring de novo MET amplification: Successful treatment with gefitinib and crizotinib.	Crizotinib	137-147	epidermal growth factor receptor	Homo sapiens	36-40
30660961-4	2019	While THP-1 cells do not respond to any of these inhibitors, CTV-1 cells are potently inhibited by dasatinib, bosutinib, crizotinib, A-770041, and WH-4-23, all potent inhibitors for Lck, a Src family kinase.	Crizotinib	121-131	LCK proto-oncogene, Src family tyrosine kinase	Homo sapiens	182-185
30797494-0	2019	Mutation tracking of a patient with EGFR-mutant lung cancer harboring de novo MET amplification: Successful treatment with gefitinib and crizotinib.	Crizotinib	137-147	SAFB like transcription modulator	Homo sapiens	78-81
30797499-0	2019	Identification of a novel WNK1-ROS1 fusion in a lung adenocarcinoma sensitive to crizotinib.	Crizotinib	81-91	WNK lysine deficient protein kinase 1	Homo sapiens	26-30
30797499-0	2019	Identification of a novel WNK1-ROS1 fusion in a lung adenocarcinoma sensitive to crizotinib.	Crizotinib	81-91	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	31-35
30797499-9	2019	When disease progressed, ROS1 G2032R mutation-a classical mechanism of crizotinib resistance-was detected in the DNA sample extracted from the patient"s plasma sample.	Crizotinib	71-81	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	25-29
30797499-10	2019	CONCLUSION: We identified a novel WNK1-ROS1 fusion that was sensitive to crizotinib and developed an ROS1 G2032R mutation when the disease progressed.	Crizotinib	73-83	WNK lysine deficient protein kinase 1	Homo sapiens	34-38
30797499-10	2019	CONCLUSION: We identified a novel WNK1-ROS1 fusion that was sensitive to crizotinib and developed an ROS1 G2032R mutation when the disease progressed.	Crizotinib	73-83	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	39-43
30797499-10	2019	CONCLUSION: We identified a novel WNK1-ROS1 fusion that was sensitive to crizotinib and developed an ROS1 G2032R mutation when the disease progressed.	Crizotinib	73-83	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	101-105
30867736-7	2019	ALK-positive patients treated with crizotinib, who exhibited high levels of p-c-Kit had significantly lower progression-free survival times than those with low levels.	Crizotinib	35-45	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	78-83
30882666-0	2019	ALK-rearranged lung adenocarcinoma patient with development of severe sinus bradycardia after treatment with crizotinib: A case report.	Crizotinib	109-119	ALK receptor tyrosine kinase	Homo sapiens	0-3
30882666-2	2019	Crizotinib, as an ALK inhibitor, has been used in the treatment of ALK-rearranged NSCLC for several years and some adverse effects should be given attention.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	18-21
30882666-2	2019	Crizotinib, as an ALK inhibitor, has been used in the treatment of ALK-rearranged NSCLC for several years and some adverse effects should be given attention.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	67-70
30867736-7	2019	ALK-positive patients treated with crizotinib, who exhibited high levels of p-c-Kit had significantly lower progression-free survival times than those with low levels.	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	0-3
30867785-0	2019	Clinicopathological features and clinical efficacy of crizotinib in Chinese patients with ROS1-positive non-small cell lung cancer.	Crizotinib	54-64	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	90-94
30867785-2	2019	The present study explored the clinicopathological features and clinical efficacy of crizotinib in patients with ROS1-positive NSCLC.	Crizotinib	85-95	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	113-117
30867785-16	2019	In conclusion, the rate of ROS1 fusion in NSCLC among the patients is low, and crizotinib is an effective and safe drug for the treatment of ROS1-positive advanced NSCLC.	Crizotinib	79-89	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	141-145
30867736-9	2019	Furthermore, multivariate analysis indicated that high levels of p-c-Kit in patients with ALK fusion was the only significant predictive factor for crizotinib efficacy and was a prognostic factor for poor overall survival time.	Crizotinib	148-158	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	67-72
30867736-9	2019	Furthermore, multivariate analysis indicated that high levels of p-c-Kit in patients with ALK fusion was the only significant predictive factor for crizotinib efficacy and was a prognostic factor for poor overall survival time.	Crizotinib	148-158	ALK receptor tyrosine kinase	Homo sapiens	90-93
30867736-12	2019	c-Kit signaling activation may be associated with poor efficacy of crizotinib and poor prognosis in advanced ALK fusion NSCLC.	Crizotinib	67-77	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	0-5
30867766-3	2019	The ALK inhibitor, crizotinib, failed to control the tumor and the patient died of the disease.	Crizotinib	19-29	ALK receptor tyrosine kinase	Homo sapiens	4-7
30863492-3	2019	The de novo mode of cetuximab resistance in SC cells could be overcome by crizotinib, a multi-RTK inhibitor that also targets MET and RON.	Crizotinib	74-84	macrophage stimulating 1 receptor	Homo sapiens	134-137
30791921-0	2019	Crizotinib with or without an EGFR-TKI in treating EGFR-mutant NSCLC patients with acquired MET amplification after failure of EGFR-TKI therapy: a multicenter retrospective study.	Crizotinib	0-10	epidermal growth factor receptor	Homo sapiens	51-55
30791921-0	2019	Crizotinib with or without an EGFR-TKI in treating EGFR-mutant NSCLC patients with acquired MET amplification after failure of EGFR-TKI therapy: a multicenter retrospective study.	Crizotinib	0-10	epidermal growth factor receptor	Homo sapiens	51-55
30791921-2	2019	Herein we report the clinical outcomes of patients with c-MET amplification resistance to EGFR-TKIs treated with crizotinib.	Crizotinib	113-123	epidermal growth factor receptor	Homo sapiens	90-94
30791921-5	2019	We assessed the efficacy and safety of crizotinib to overcome EGFR-TKI resistance in EGFR-activating mutations NSCLC with acquired MET amplification.	Crizotinib	39-49	epidermal growth factor receptor	Homo sapiens	62-66
30791921-5	2019	We assessed the efficacy and safety of crizotinib to overcome EGFR-TKI resistance in EGFR-activating mutations NSCLC with acquired MET amplification.	Crizotinib	39-49	epidermal growth factor receptor	Homo sapiens	85-89
30791921-7	2019	Fourteen patients received crizotinib treatment after acquired resistance to EGFR-TKIs.	Crizotinib	27-37	epidermal growth factor receptor	Homo sapiens	77-81
30791921-14	2019	CONCLUSIONS: We observed the clinical evidence of efficacy generated by combination of crizotinib and previous EGFR-TKIs after the resistance to first-generation EGFR-TKIs.	Crizotinib	87-97	epidermal growth factor receptor	Homo sapiens	162-166
30352902-6	2019	In one patient, the KRAS mutation was acquired post-crizotinib, while the remaining 4 METex14 patients harbored the KRAS mutation prior to MET TKI therapy.	Crizotinib	52-62	KRAS proto-oncogene, GTPase	Homo sapiens	20-24
30804663-2	2019	Brigatinib has demonstrated a wider spectrum of preclinical activity against crizotinib-resistant ALK mutant advanced NSCLC.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	98-101
30804692-6	2019	Ten observational studies reported median overall survival of crizotinib-led sequences ranging from 30.3 to 63.75 months from initiation of crizotinib; 49.4-89.6 months from metastatic non-small-cell lung cancer diagnosis; and 15.5-22.0 months from initiation of the second-generation ALK inhibitor after initial crizotinib.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	285-288
30799936-0	2019	NCOA1-ALK: a novel ALK rearrangement in one lung adenocarcinoma patient responding to crizotinib treatment.	Crizotinib	86-96	nuclear receptor coactivator 1	Homo sapiens	0-5
30799936-0	2019	NCOA1-ALK: a novel ALK rearrangement in one lung adenocarcinoma patient responding to crizotinib treatment.	Crizotinib	86-96	ALK receptor tyrosine kinase	Homo sapiens	6-9
30799936-0	2019	NCOA1-ALK: a novel ALK rearrangement in one lung adenocarcinoma patient responding to crizotinib treatment.	Crizotinib	86-96	ALK receptor tyrosine kinase	Homo sapiens	19-22
30799936-7	2019	Our findings provide valuable information about responses to crizotinib in patients with this form of ALK rearrangement and better understanding of ALK-TKI applications.	Crizotinib	61-71	ALK receptor tyrosine kinase	Homo sapiens	102-105
30863492-7	2019	Conversely, addition of RTK ligands HGF and NRG1 induced cetuximab resistance in CC cells, which could be blocked by addition of crizotinib.	Crizotinib	129-139	hepatocyte growth factor	Homo sapiens	36-39
30863492-7	2019	Conversely, addition of RTK ligands HGF and NRG1 induced cetuximab resistance in CC cells, which could be blocked by addition of crizotinib.	Crizotinib	129-139	neuregulin 1	Homo sapiens	44-48
30771874-3	2019	METHODS: A comprehensive systematic review of literature has been conducted to include prospective trials that used the ALK inhibitors Crizotinib, Ceritinib, Alectinib, Brigatinib and Lorlatinib in patients with advanced NSCLC and have available efficacy and toxicity results.	Crizotinib	135-145	ALK receptor tyrosine kinase	Homo sapiens	120-123
30709876-0	2019	Refractory and metastatic infantile fibrosarcoma harboring LMNA-NTRK1 fusion shows complete and durable response to crizotinib.	Crizotinib	116-126	lamin A/C	Homo sapiens	59-63
30709876-0	2019	Refractory and metastatic infantile fibrosarcoma harboring LMNA-NTRK1 fusion shows complete and durable response to crizotinib.	Crizotinib	116-126	neurotrophic receptor tyrosine kinase 1	Homo sapiens	64-69
30709876-4	2019	In this report, we outline the use of integrative clinical sequencing (ICS) including RNA-seq in a patient with refractory, metastatic IFS to reveal an unusual fusion (LMNA-NTRK1), not detected by routine FISH testing, which was treated with oral crizotinib and resulted in a complete and durable long-term response.	Crizotinib	247-257	lamin A/C	Homo sapiens	168-172
30709876-4	2019	In this report, we outline the use of integrative clinical sequencing (ICS) including RNA-seq in a patient with refractory, metastatic IFS to reveal an unusual fusion (LMNA-NTRK1), not detected by routine FISH testing, which was treated with oral crizotinib and resulted in a complete and durable long-term response.	Crizotinib	247-257	neurotrophic receptor tyrosine kinase 1	Homo sapiens	173-178
30771874-6	2019	There were differences in the toxicity patterns between the different ALK inhibitors with more GI and hepatic toxicities with Ceritinib, more visual disorders with Crizotinib, more dysgeusia with crizotinib and Alectinib and possibly more respiratory complications with Brigatinib.	Crizotinib	164-174	ALK receptor tyrosine kinase	Homo sapiens	70-73
30771874-6	2019	There were differences in the toxicity patterns between the different ALK inhibitors with more GI and hepatic toxicities with Ceritinib, more visual disorders with Crizotinib, more dysgeusia with crizotinib and Alectinib and possibly more respiratory complications with Brigatinib.	Crizotinib	196-206	ALK receptor tyrosine kinase	Homo sapiens	70-73
30463991-8	2019	Among three MET-amplified cell lines, one cell line was sensitive to a combination of osimertinib and crizotinib.	Crizotinib	102-112	SAFB like transcription modulator	Homo sapiens	12-15
30642440-0	2019	Case report: Crizotinib is effective in a patient with ROS1-rearranged pulmonary inflammatory myofibroblastic tumor.	Crizotinib	13-23	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	55-59
30642440-7	2019	The patient achieved continuous remission after treatment with crizotinib (250 mg, bid).	Crizotinib	63-73	BH3 interacting domain death agonist	Homo sapiens	83-86
30649748-3	2019	To date, two small molecule c-MET inhibitors, cabozantinib and crizotinib, have been approved by regulatory authorities for the treatment of selected cancer types, but several novel c-MET inhibitors (either monoclonal antibodies or small molecule c-MET tyrosine kinase inhibitors) and treatment combinations are currently under study in different settings.	Crizotinib	63-73	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	28-33
30412912-10	2019	KRAS mutant cell lines LoVo, HCT116, and DLD1 were resistant to cetuximab but sensitive to crizotinib.	Crizotinib	91-101	KRAS proto-oncogene, GTPase	Homo sapiens	0-4
30675302-0	2019	ALK-G1269A mutation in epithelioid inflammatory myofibroblastic sarcoma after progression on crizotinib: A case report.	Crizotinib	93-103	ALK receptor tyrosine kinase	Homo sapiens	0-3
30675302-4	2019	Herein, a chromosomal ALK-G1269A mutation was identified using next-generation sequencing (NGS) and the mutation was confirmed by Sanger sequencing in a patient with crizotinib-resistant EIMS who benefited from treatment with the second-generation ALK inhibitor AP26113.	Crizotinib	166-176	ALK receptor tyrosine kinase	Homo sapiens	22-25
30675302-4	2019	Herein, a chromosomal ALK-G1269A mutation was identified using next-generation sequencing (NGS) and the mutation was confirmed by Sanger sequencing in a patient with crizotinib-resistant EIMS who benefited from treatment with the second-generation ALK inhibitor AP26113.	Crizotinib	166-176	ALK receptor tyrosine kinase	Homo sapiens	248-251
30412912-12	2019	Immunoblot analysis showed that crizotinib blocked radiation-induced c-Met phosphorylation and attenuated downstream signaling pathways.	Crizotinib	32-42	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	69-74
30412912-14	2019	Additionally, crizotinib completely blocked HGF induced cell migration.	Crizotinib	14-24	hepatocyte growth factor	Homo sapiens	44-47
30412912-15	2019	CONCLUSIONS: Inhibition of c-Met with crizotinib effectively sensitizes cetuximab-resistant KRAS mutant colorectal cancer cell lines to radiation.	Crizotinib	38-48	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	27-32
30412912-15	2019	CONCLUSIONS: Inhibition of c-Met with crizotinib effectively sensitizes cetuximab-resistant KRAS mutant colorectal cancer cell lines to radiation.	Crizotinib	38-48	KRAS proto-oncogene, GTPase	Homo sapiens	92-96
30915158-2	2019	Crizotinib is very effective in ROS1-positive patients and is now Food and Drug Administration (FDA) approved for the treatment of patients with advanced ROS1-positive NSCLC.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	32-36
30915158-2	2019	Crizotinib is very effective in ROS1-positive patients and is now Food and Drug Administration (FDA) approved for the treatment of patients with advanced ROS1-positive NSCLC.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	154-158
30692572-3	2019	Inhibitors of MTH1 (TH588 and (S)-crizotinib) were shown to reduce cancer cell viability.	Crizotinib	30-44	nudix hydrolase 1	Homo sapiens	14-18
30692572-7	2019	(S)-crizotinib reduced tyrosine phosphorylation of c-MET and ErbB3 whereas TH588 induced a mitotic cell cycle arrest, which was not affected by adding ROS-modulating compounds.	Crizotinib	0-14	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	51-56
30692572-7	2019	(S)-crizotinib reduced tyrosine phosphorylation of c-MET and ErbB3 whereas TH588 induced a mitotic cell cycle arrest, which was not affected by adding ROS-modulating compounds.	Crizotinib	0-14	erb-b2 receptor tyrosine kinase 3	Homo sapiens	61-66
30687633-4	2018	Materials and Methods: A comprehensive search was conducted using electronic databases of PubMed, Medline and Cochrane Library to identify the studies involving comparison of ALK inhibitors to chemotherapy and Next generation ALK inhibitors to crizotinib.	Crizotinib	244-254	ALK receptor tyrosine kinase	Homo sapiens	175-178
30687633-4	2018	Materials and Methods: A comprehensive search was conducted using electronic databases of PubMed, Medline and Cochrane Library to identify the studies involving comparison of ALK inhibitors to chemotherapy and Next generation ALK inhibitors to crizotinib.	Crizotinib	244-254	ALK receptor tyrosine kinase	Homo sapiens	226-229
30687633-8	2018	ALK inhibitors including crizotinib, ceritinib and alectinib revealed significantly better PFS (HR 0.42 [0.35, 0.50; p < 0.00001]), ORR (Overall OR 6.59 [4.86, 8.94; p < 0.00001] as compared to chemotherapy in the first line as well as second line treatment settings.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	0-3
30719217-5	2019	Similar to other rearrangements involving ROS1, the resulting fusion protein is believed to act as a major driver of carcinogenesis and may be subject to inhibition by drugs that target ROS1 such as crizotinib.	Crizotinib	199-209	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	42-46
30719217-5	2019	Similar to other rearrangements involving ROS1, the resulting fusion protein is believed to act as a major driver of carcinogenesis and may be subject to inhibition by drugs that target ROS1 such as crizotinib.	Crizotinib	199-209	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	186-190
30350109-5	2019	In vitro analysis demonstrated the oncogenic activity of this fusion, which was suppressed by the ALK/ROS1 inhibitor, crizotinib.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	98-101
30350109-5	2019	In vitro analysis demonstrated the oncogenic activity of this fusion, which was suppressed by the ALK/ROS1 inhibitor, crizotinib.	Crizotinib	118-128	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	102-106
30422759-0	2019	Responses to crizotinib can occur in c-MET overexpressing nonsmall cell lung cancer after developing EGFR-TKI resistance.	Crizotinib	13-23	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	37-42
30422759-0	2019	Responses to crizotinib can occur in c-MET overexpressing nonsmall cell lung cancer after developing EGFR-TKI resistance.	Crizotinib	13-23	epidermal growth factor receptor	Homo sapiens	101-105
30744539-0	2019	Case report: HER2 amplification as a resistance mechanism to crizotinib in NSCLC with MET exon 14 skipping.	Crizotinib	61-71	erb-b2 receptor tyrosine kinase 2	Homo sapiens	13-17
30744539-4	2019	Then, amplification of multiple genes such as erb-b2 receptor tyrosine kinase 2 (HER2) was detected when disease progressed, indicating novel resistance mechanisms to crizotinib.	Crizotinib	167-177	erb-b2 receptor tyrosine kinase 2	Homo sapiens	81-85
30744539-6	2019	This was the first NSCLC case with MET exon 14 skipping which reported the HER2 gene amplification at the time of progression during crizotinib treatment, indicating that bypass mechanisms contribute to the development of acquired resistance to MET inhibitors.	Crizotinib	133-143	erb-b2 receptor tyrosine kinase 2	Homo sapiens	75-79
31131689-3	2019	Here, we report the patient with primary dual MET/EGFR mutation treated with icotinib shows a disease progression, but the chest computed tomography shows the mass has significantly shrunk after 3 weeks of single-agent crizotinib.	Crizotinib	219-229	epidermal growth factor receptor	Homo sapiens	50-54
30412912-0	2019	Enhancing the Radiation Response in KRAS Mutant Colorectal Cancers Using the c-Met Inhibitor Crizotinib.	Crizotinib	93-103	KRAS proto-oncogene, GTPase	Homo sapiens	36-40
30412912-0	2019	Enhancing the Radiation Response in KRAS Mutant Colorectal Cancers Using the c-Met Inhibitor Crizotinib.	Crizotinib	93-103	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	77-82
30412912-2	2019	In this study, we used a small molecule inhibitor of c-Met, crizotinib, in cetuximab-resistant, mutant KRAS-driven colorectal cancer cell lines and assessed radiosensitization.	Crizotinib	60-70	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	53-58
30412912-2	2019	In this study, we used a small molecule inhibitor of c-Met, crizotinib, in cetuximab-resistant, mutant KRAS-driven colorectal cancer cell lines and assessed radiosensitization.	Crizotinib	60-70	KRAS proto-oncogene, GTPase	Homo sapiens	103-107
30412912-6	2019	Immunoblot analysis was used to determine the effect of crizotinib on c-Met and downstream pathways and DNA damage response.	Crizotinib	56-66	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	70-75
30191596-0	2019	Molecular inhibitory mechanism study on the potent inhibitor brigatinib against four crizotinib-resistant ALK mutations.	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	106-109
30642448-0	2019	Exploration of germline variants responsible for adverse events of crizotinib in anaplastic lymphoma kinase-positive non-small cell lung cancer by target-gene panel sequencing.	Crizotinib	67-77	ALK receptor tyrosine kinase	Homo sapiens	81-107
30642448-1	2019	OBJECTIVES: Crizotinib is a standard treatment for advanced anaplastic lymphoma kinase (ALK)- or ROS1-fusion-gene-positive non-small cell lung cancer; however, serious adverse events (AEs), including elevated alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and interstitial lung disease (ILD), develop occasionally.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	60-86
30642448-1	2019	OBJECTIVES: Crizotinib is a standard treatment for advanced anaplastic lymphoma kinase (ALK)- or ROS1-fusion-gene-positive non-small cell lung cancer; however, serious adverse events (AEs), including elevated alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and interstitial lung disease (ILD), develop occasionally.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	88-91
30642448-1	2019	OBJECTIVES: Crizotinib is a standard treatment for advanced anaplastic lymphoma kinase (ALK)- or ROS1-fusion-gene-positive non-small cell lung cancer; however, serious adverse events (AEs), including elevated alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and interstitial lung disease (ILD), develop occasionally.	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	97-101
30642448-1	2019	OBJECTIVES: Crizotinib is a standard treatment for advanced anaplastic lymphoma kinase (ALK)- or ROS1-fusion-gene-positive non-small cell lung cancer; however, serious adverse events (AEs), including elevated alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and interstitial lung disease (ILD), develop occasionally.	Crizotinib	12-22	glutamic--pyruvic transaminase	Homo sapiens	209-233
30642448-1	2019	OBJECTIVES: Crizotinib is a standard treatment for advanced anaplastic lymphoma kinase (ALK)- or ROS1-fusion-gene-positive non-small cell lung cancer; however, serious adverse events (AEs), including elevated alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and interstitial lung disease (ILD), develop occasionally.	Crizotinib	12-22	solute carrier family 17 member 5	Homo sapiens	268-271
30642448-8	2019	CONCLUSION: Nonsynonymous EPHX1 and TCF7L2 SNVs might be associated with clinically significant crizotinib-associated AEs.	Crizotinib	96-106	epoxide hydrolase 1	Homo sapiens	26-31
30642448-8	2019	CONCLUSION: Nonsynonymous EPHX1 and TCF7L2 SNVs might be associated with clinically significant crizotinib-associated AEs.	Crizotinib	96-106	transcription factor 7 like 2	Homo sapiens	36-42
31359737-8	2019	Furthermore, beta-GP increased c-Met phosphorylation at day 21, an effect ameliorated by C2 and C4 and the c-Met inhibitor, crizotinib.	Crizotinib	124-134	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	31-36
31359737-8	2019	Furthermore, beta-GP increased c-Met phosphorylation at day 21, an effect ameliorated by C2 and C4 and the c-Met inhibitor, crizotinib.	Crizotinib	124-134	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	107-112
31359737-9	2019	We next interrogated the effects of the Notch inhibitor DAPT and confirmed an inhibition of beta-GP up-regulated Notch3 protein by C2, DAPT and crizotinib compared to controls.	Crizotinib	144-154	notch receptor 3	Homo sapiens	113-119
28669346-0	2019	Crizotinib Versus Chemotherapy on ALK-positive NSCLC: A Systematic Review of Efficacy and Safety.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	34-37
28669346-1	2019	INTRODUCTION: Crizotinib was approved to treat anaplastic lymphoma kinase (ALK)- positive non-small cell lung cancer (NSCLC) by the Food and Drug Administration in 2011.We conducted a systematic review of clinical trials and retrospective studies to compare the efficacy and safety of crizotinib with chemotherapy.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	47-73
28669346-1	2019	INTRODUCTION: Crizotinib was approved to treat anaplastic lymphoma kinase (ALK)- positive non-small cell lung cancer (NSCLC) by the Food and Drug Administration in 2011.We conducted a systematic review of clinical trials and retrospective studies to compare the efficacy and safety of crizotinib with chemotherapy.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	75-78
28669346-14	2019	Crizotinib treatment would be a favorable treatment option for patients with ALK-positive NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	77-80
30381078-0	2019	CT-707 Overcomes Resistance of Crizotinib through Activating PDPK1- AKT1 Pathway by Targeting FAK.	Crizotinib	31-41	3-phosphoinositide dependent protein kinase 1	Homo sapiens	61-66
30381078-0	2019	CT-707 Overcomes Resistance of Crizotinib through Activating PDPK1- AKT1 Pathway by Targeting FAK.	Crizotinib	31-41	AKT serine/threonine kinase 1	Homo sapiens	68-72
30381078-0	2019	CT-707 Overcomes Resistance of Crizotinib through Activating PDPK1- AKT1 Pathway by Targeting FAK.	Crizotinib	31-41	protein tyrosine kinase 2	Homo sapiens	94-97
30381078-5	2019	RESULTS: Importantly, our study provided evidence that CT-707 overcomes resistance to crizotinib through activating PDPK1-AKT1 pathway by targeting FAK.	Crizotinib	86-96	3-phosphoinositide dependent protein kinase 1	Homo sapiens	116-121
30381078-5	2019	RESULTS: Importantly, our study provided evidence that CT-707 overcomes resistance to crizotinib through activating PDPK1-AKT1 pathway by targeting FAK.	Crizotinib	86-96	AKT serine/threonine kinase 1	Homo sapiens	122-126
30381078-5	2019	RESULTS: Importantly, our study provided evidence that CT-707 overcomes resistance to crizotinib through activating PDPK1-AKT1 pathway by targeting FAK.	Crizotinib	86-96	protein tyrosine kinase 2	Homo sapiens	148-151
30362839-0	2019	Comparative efficacy of first-line ceritinib and crizotinib in advanced or metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer: an adjusted indirect comparison with external controls.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	86-112
30191596-3	2019	Comparison between ALK-brigatinib and ALK-crizotinib suggests that the scaffold of brigatinib is well anchored to the residue Met1199 of hinge region by two hydrogen bonds, and the residue Lys1150 has the strong electrostatic interaction with the dimethylphosphine oxide moiety in brigatinib.	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	38-41
29081033-11	2019	Crizotinib treatment had a long-term effect in ALK positive IMT patients, however itwas only temporary efficient in relapsed, progressive STS and NBL.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	47-50
30205166-4	2019	METHODS: Patients with advanced ALK receptor tyrosine kinase (ALK)-driven, ROS1-driven, or MET proto-oncogene, receptor tyrosine kinase (MET)-driven NSCLC treated with crizotinib, with or without preceding ICI therapy, were identified.	Crizotinib	168-178	ALK receptor tyrosine kinase	Homo sapiens	32-35
30205166-4	2019	METHODS: Patients with advanced ALK receptor tyrosine kinase (ALK)-driven, ROS1-driven, or MET proto-oncogene, receptor tyrosine kinase (MET)-driven NSCLC treated with crizotinib, with or without preceding ICI therapy, were identified.	Crizotinib	168-178	SAFB like transcription modulator	Homo sapiens	0-3
30205166-6	2019	RESULTS: We identified 453 patients who had NSCLC with an oncogenic alteration in ALK receptor tyrosine kinase gene (ALK), ROS1, or MET proto-oncogene, receptor tyrosine kinase gene (MET) and were treated with crizotinib (11 with and 442 without prior ICI therapy).	Crizotinib	210-220	ALK receptor tyrosine kinase	Homo sapiens	82-85
30161279-1	2019	Drug resistance to anaplastic lymphoma kinase (ALK) inhibitors (crizotinib and ceritinib) is caused by mutation in the region encoding kinase domain of ALK.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	19-45
30161279-1	2019	Drug resistance to anaplastic lymphoma kinase (ALK) inhibitors (crizotinib and ceritinib) is caused by mutation in the region encoding kinase domain of ALK.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	47-50
30161279-1	2019	Drug resistance to anaplastic lymphoma kinase (ALK) inhibitors (crizotinib and ceritinib) is caused by mutation in the region encoding kinase domain of ALK.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	152-155
30642546-1	2019	OBJECTIVES: ALK tyrosine kinase inhibitors (TKIs), including crizotinib and several next generation TKIs, have demonstrated beneficial clinical outcomes in ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	61-71	ALK receptor tyrosine kinase	Homo sapiens	12-15
30642546-1	2019	OBJECTIVES: ALK tyrosine kinase inhibitors (TKIs), including crizotinib and several next generation TKIs, have demonstrated beneficial clinical outcomes in ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	61-71	ALK receptor tyrosine kinase	Homo sapiens	156-159
30642546-5	2019	Half of the patients harbored ALK activating mutations upon progression on crizotinib treatment.	Crizotinib	75-85	ALK receptor tyrosine kinase	Homo sapiens	30-33
30642546-7	2019	Specifically, ALK G1269 A, L1196 M, and C1156Y substitutions were more common in crizotinib-alone samples, while ALK G1202R was significantly more enriched post-multi-TKIs (P = 0.009).	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	14-17
30642546-9	2019	Furthermore, dual activation of ALK and bypass signaling was more frequently found in the multi-TKIs group (5/17, 29%) in contrast to crizotinib-alone (2/35, 6%) (P = 0.031).	Crizotinib	134-144	ALK receptor tyrosine kinase	Homo sapiens	32-35
30642546-10	2019	Additionally, concurrent TP53 mutation demonstrated significantly shorter progression-free survival (PFS) compared with TP53 wildtype in crizotinib-alone group (median PFS: 8 vs 13 months, Hazard Ratio = 1.494, P = 0.019).	Crizotinib	137-147	tumor protein p53	Homo sapiens	25-29
30642546-11	2019	CONCLUSION: Concurrent ALK activating mutations and/or upregulated bypass signaling are more enriched in patients undergoing multiple ALK TKI treatments compared to crizotinib alone.	Crizotinib	165-175	ALK receptor tyrosine kinase	Homo sapiens	23-26
30642546-11	2019	CONCLUSION: Concurrent ALK activating mutations and/or upregulated bypass signaling are more enriched in patients undergoing multiple ALK TKI treatments compared to crizotinib alone.	Crizotinib	165-175	ALK receptor tyrosine kinase	Homo sapiens	134-137
30290287-0	2019	MYC Amplification as a Potential Mechanism of Primary Resistance to Crizotinib in ALK-Rearranged Non-Small Cell Lung Cancer: A Brief Report.	Crizotinib	68-78	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	0-3
31527380-7	2019	SUMMARY: According to some retrospective trials, for ALKi-naive ALK rearrangement NSCLC patients with brain metastasis, crizotinib together with radiotherapy seem to improve intracranial control rate, progression-free survival, and very likely improve overall survival; next-generation ALK-TKIs are now replacing crizotinib as first-line treatment.	Crizotinib	120-130	ALK receptor tyrosine kinase	Homo sapiens	53-56
31527380-7	2019	SUMMARY: According to some retrospective trials, for ALKi-naive ALK rearrangement NSCLC patients with brain metastasis, crizotinib together with radiotherapy seem to improve intracranial control rate, progression-free survival, and very likely improve overall survival; next-generation ALK-TKIs are now replacing crizotinib as first-line treatment.	Crizotinib	120-130	ALK receptor tyrosine kinase	Homo sapiens	64-67
31527380-9	2019	Second-/third-generation ALK inhibitors had higher intracranial ORR and DCR even after crizotinib-refractory situations, and they alone had a strong efficacy against intracranial tumors, in which situation radiotherapy might be omitted.	Crizotinib	87-97	ALK receptor tyrosine kinase	Homo sapiens	25-28
31527380-13	2019	Key Messages: Next-generation ALK-TKIs are now replacing crizotinib as first-line treatment in ALKi-naive ALK rearrangement NSCLC patients with brain metastasis, and they alone might have a strong efficacy against intracranial tumors in crizotinib-refractory situations in which occasion radiotherapy might be omitted.	Crizotinib	237-247	ALK receptor tyrosine kinase	Homo sapiens	30-33
30290287-0	2019	MYC Amplification as a Potential Mechanism of Primary Resistance to Crizotinib in ALK-Rearranged Non-Small Cell Lung Cancer: A Brief Report.	Crizotinib	68-78	ALK receptor tyrosine kinase	Homo sapiens	82-85
30290287-1	2019	INTRODUCTION: Translocations of the anaplastic lymphoma kinase (ALK) can be effectively targeted in advanced non-small cell lung cancer by ALK-TKI inhibitors including Crizotinib.	Crizotinib	168-178	ALK receptor tyrosine kinase	Homo sapiens	36-62
30290287-1	2019	INTRODUCTION: Translocations of the anaplastic lymphoma kinase (ALK) can be effectively targeted in advanced non-small cell lung cancer by ALK-TKI inhibitors including Crizotinib.	Crizotinib	168-178	ALK receptor tyrosine kinase	Homo sapiens	64-67
30290287-1	2019	INTRODUCTION: Translocations of the anaplastic lymphoma kinase (ALK) can be effectively targeted in advanced non-small cell lung cancer by ALK-TKI inhibitors including Crizotinib.	Crizotinib	168-178	ALK receptor tyrosine kinase	Homo sapiens	139-142
30290287-8	2019	Human EML4-ALK rearranged cells infected with a lentiviral vector carrying full-length human MYC cDNA were treated in vitro with crizotinib and alectinib.	Crizotinib	129-139	EMAP like 4	Homo sapiens	6-10
30290287-8	2019	Human EML4-ALK rearranged cells infected with a lentiviral vector carrying full-length human MYC cDNA were treated in vitro with crizotinib and alectinib.	Crizotinib	129-139	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	93-96
30118545-0	2018	Synthesis of deuterium-labeled crizotinib, a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK).	Crizotinib	31-41	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	126-131
30786826-3	2019	Crizotinib was the first ALK inhibitor developed and it demonstrated improved outcomes in patients with ALK-positive advanced NSCLC in comparison with chemotherapy.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	25-28
30786826-3	2019	Crizotinib was the first ALK inhibitor developed and it demonstrated improved outcomes in patients with ALK-positive advanced NSCLC in comparison with chemotherapy.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	104-107
30786826-4	2019	However, despite an initial response, all ALK-positive NSCLC patients develop acquired resistance to crizotinib.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	42-45
30466782-7	2018	A comprehensive analysis of tyrosine phosphorylation in receptor tyrosine kinases in combination with small molecule chemical library screening revealed upregulated c-MET phosphorylation in this resistance cell line with elevated sensitivity to c-MET TKI (crizotinib) and PI3K/mTOR dual inhibitor (BEZ235).	Crizotinib	256-266	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	165-170
30466782-7	2018	A comprehensive analysis of tyrosine phosphorylation in receptor tyrosine kinases in combination with small molecule chemical library screening revealed upregulated c-MET phosphorylation in this resistance cell line with elevated sensitivity to c-MET TKI (crizotinib) and PI3K/mTOR dual inhibitor (BEZ235).	Crizotinib	256-266	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	245-250
30466782-7	2018	A comprehensive analysis of tyrosine phosphorylation in receptor tyrosine kinases in combination with small molecule chemical library screening revealed upregulated c-MET phosphorylation in this resistance cell line with elevated sensitivity to c-MET TKI (crizotinib) and PI3K/mTOR dual inhibitor (BEZ235).	Crizotinib	256-266	mechanistic target of rapamycin kinase	Homo sapiens	277-281
30339198-0	2018	Identification of a novel crizotinib-sensitive MET-ATXN7L1 gene fusion variant in lung adenocarcinoma by next generation sequencing.	Crizotinib	26-36	ataxin 7 like 1	Homo sapiens	51-58
30025202-1	2018	Crizotinib, a drug for anaplastic lymphoma kinase (ALK) positive and c-ros oncogene 1 receptor tyrosine kinase (ROS1) positive non-small cell lung cancer (NSCLC), was structurally optimized via a strategy of structure-based fragment replacing.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	23-49
30025202-1	2018	Crizotinib, a drug for anaplastic lymphoma kinase (ALK) positive and c-ros oncogene 1 receptor tyrosine kinase (ROS1) positive non-small cell lung cancer (NSCLC), was structurally optimized via a strategy of structure-based fragment replacing.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	51-54
30025202-1	2018	Crizotinib, a drug for anaplastic lymphoma kinase (ALK) positive and c-ros oncogene 1 receptor tyrosine kinase (ROS1) positive non-small cell lung cancer (NSCLC), was structurally optimized via a strategy of structure-based fragment replacing.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	69-110
30025202-1	2018	Crizotinib, a drug for anaplastic lymphoma kinase (ALK) positive and c-ros oncogene 1 receptor tyrosine kinase (ROS1) positive non-small cell lung cancer (NSCLC), was structurally optimized via a strategy of structure-based fragment replacing.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	112-116
30025202-2	2018	Computational study showed it was beneficial for interaction of crizotinib and ALK to increase the distance between pyridyl ring and phenyl ring in crizotinib, and thus, a series of novel glycol diaryl ethers were synthesized.	Crizotinib	148-158	ALK receptor tyrosine kinase	Homo sapiens	79-82
30657798-5	2018	We describe a case of lichenoid drug eruption (LDE) that appeared 4 weeks after initiation of treatment with crizotinib in a 61-year-old man with ALK-positive metastatic lung adenocarcinoma.	Crizotinib	109-119	ALK receptor tyrosine kinase	Homo sapiens	146-149
30555260-0	2018	Efficacy and safety of crizotinib in patients with anaplastic lymphoma kinase-positive advanced-stage non-small-cell lung cancer.	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	51-77
30555260-4	2018	Crizotinib, a tyrosine kinase inhibitor (TKI), was approved by the Food and Drug Administration (FDA) in 2011 for the treatment of advanced ALK-positive non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	140-143
30555260-6	2018	Crizotinib 250 mg BID was given orally with/without food intake.	Crizotinib	0-10	BH3 interacting domain death agonist	Homo sapiens	18-21
30555260-12	2018	Conclusion: In NSCLC, crizotinib is a viable treatment option with good response and tolerable toxicity for patients with ALK-positive advanced disease.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	122-125
30477470-0	2018	Crizotinib in advanced non-small-cell lung cancer with concomitant ALK rearrangement and c-Met overexpression.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	67-70
30477470-0	2018	Crizotinib in advanced non-small-cell lung cancer with concomitant ALK rearrangement and c-Met overexpression.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	89-94
30477470-1	2018	OBJECTIVE: Crizotinib can target against mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK), which has been considered as a multi-targeted tyrosine kinase inhibitor (TKI).	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	85-111
30477470-1	2018	OBJECTIVE: Crizotinib can target against mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK), which has been considered as a multi-targeted tyrosine kinase inhibitor (TKI).	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	113-116
30477470-2	2018	The objective of this study was to explore the efficacy of crizotinib in advanced non-small-cell lung cancer (NSCLC) with concomitant ALK rearrangement and c-Met overexpression.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	134-137
30477470-2	2018	The objective of this study was to explore the efficacy of crizotinib in advanced non-small-cell lung cancer (NSCLC) with concomitant ALK rearrangement and c-Met overexpression.	Crizotinib	59-69	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	156-161
30477470-5	2018	The efficacy of crizotinib was explored in the ALK-rearranged patients with or without c-Met overexpression.	Crizotinib	16-26	ALK receptor tyrosine kinase	Homo sapiens	47-50
30477470-5	2018	The efficacy of crizotinib was explored in the ALK-rearranged patients with or without c-Met overexpression.	Crizotinib	16-26	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	87-92
30477470-7	2018	A total of 116 ALK-rearranged patients received the treatment of crizotinib.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	15-18
30519133-3	2018	Here, we report a novel VKORC1L1-ALK fusion and an ALK T1151K resistance mutation detected in a lung cancer patient who had been on crizotinib for over 8 years.	Crizotinib	132-142	vitamin K epoxide reductase complex subunit 1 like 1	Homo sapiens	24-32
30519133-3	2018	Here, we report a novel VKORC1L1-ALK fusion and an ALK T1151K resistance mutation detected in a lung cancer patient who had been on crizotinib for over 8 years.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	33-36
30519133-3	2018	Here, we report a novel VKORC1L1-ALK fusion and an ALK T1151K resistance mutation detected in a lung cancer patient who had been on crizotinib for over 8 years.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	51-54
30071258-2	2018	These data are supported by some clinical studies, which showed improved responses to crizotinib in non-small cell lung cancer (NSCLC) patients carrying particular variants of ALK translocation.	Crizotinib	86-96	ALK receptor tyrosine kinase	Homo sapiens	176-179
29877262-2	2018	We herein report the case of a lung cancer patient with carcinomatous meningitis who had an ALK I1171T resistance mutation revealed by direct DNA sequencing of the cerebrospinal fluid after treatment with cytotoxic chemotherapy, crizotinib, and alectinib.	Crizotinib	229-239	ALK receptor tyrosine kinase	Homo sapiens	92-95
29981925-5	2018	We measured progression-free survival and time to CNS progression in ROS1-positive and ALK-positive patients who were taking crizotinib.	Crizotinib	125-135	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	69-73
29981925-5	2018	We measured progression-free survival and time to CNS progression in ROS1-positive and ALK-positive patients who were taking crizotinib.	Crizotinib	125-135	ALK receptor tyrosine kinase	Homo sapiens	87-90
29981925-13	2018	The CNS is a common first site of progression in ROS1-positive patients who are taking crizotinib.	Crizotinib	87-97	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	49-53
30010043-0	2018	CUX1-ALK, a Novel ALK Rearrangement That Responds to Crizotinib in Non-Small Cell Lung Cancer.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	5-8
30010043-0	2018	CUX1-ALK, a Novel ALK Rearrangement That Responds to Crizotinib in Non-Small Cell Lung Cancer.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	18-21
30010043-3	2018	The most common ALK rearrangement is echinoderm microtubule associated protein like 4 (EML4)-ALK, with several variants that can be targeted by the tyrosine kinase inhibitor crizotinib.	Crizotinib	174-184	ALK receptor tyrosine kinase	Homo sapiens	16-19
30010043-3	2018	The most common ALK rearrangement is echinoderm microtubule associated protein like 4 (EML4)-ALK, with several variants that can be targeted by the tyrosine kinase inhibitor crizotinib.	Crizotinib	174-184	EMAP like 4	Homo sapiens	87-91
30010043-3	2018	The most common ALK rearrangement is echinoderm microtubule associated protein like 4 (EML4)-ALK, with several variants that can be targeted by the tyrosine kinase inhibitor crizotinib.	Crizotinib	174-184	ALK receptor tyrosine kinase	Homo sapiens	93-96
30010043-8	2018	Expression of the cut-like homeobox 1-ALK fusion protein in 293T cells confirmed the self-phosphorylation of the fusion protein and the activation of ALK downstream signaling pathways, including the mitogen-activated protein kinase, Janus kinase-signal transducer and activator of transcription, and phosphoinositide 3-kinase/AKT signaling pathways, which could all be inhibited by the addition of crizotinib.	Crizotinib	398-408	cut like homeobox 1	Homo sapiens	18-37
30010043-8	2018	Expression of the cut-like homeobox 1-ALK fusion protein in 293T cells confirmed the self-phosphorylation of the fusion protein and the activation of ALK downstream signaling pathways, including the mitogen-activated protein kinase, Janus kinase-signal transducer and activator of transcription, and phosphoinositide 3-kinase/AKT signaling pathways, which could all be inhibited by the addition of crizotinib.	Crizotinib	398-408	ALK receptor tyrosine kinase	Homo sapiens	38-41
30010043-8	2018	Expression of the cut-like homeobox 1-ALK fusion protein in 293T cells confirmed the self-phosphorylation of the fusion protein and the activation of ALK downstream signaling pathways, including the mitogen-activated protein kinase, Janus kinase-signal transducer and activator of transcription, and phosphoinositide 3-kinase/AKT signaling pathways, which could all be inhibited by the addition of crizotinib.	Crizotinib	398-408	ALK receptor tyrosine kinase	Homo sapiens	150-153
30642546-12	2019	Concomitant TP53 mutation correlated to unfavorable survival when receiving a single TKI crizotinib.	Crizotinib	89-99	tumor protein p53	Homo sapiens	12-16
29515255-5	2018	Accordingly, the combination of the ALK/MET inhibitor crizotinib and selective HDAC8 inhibitors (3-6 microM PCI-34051 or 10 microM 20a) efficiently killed neuroblastoma cell lines carrying wildtype ALK (SK-N-BE(2)-C, IMR5/75), amplified ALK (NB-1), and those carrying the activating ALK F1174L mutation (Kelly), and, in cells carrying the activating R1275Q mutation (LAN-5), combination treatment decreased viable cell count.	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	36-39
29515255-5	2018	Accordingly, the combination of the ALK/MET inhibitor crizotinib and selective HDAC8 inhibitors (3-6 microM PCI-34051 or 10 microM 20a) efficiently killed neuroblastoma cell lines carrying wildtype ALK (SK-N-BE(2)-C, IMR5/75), amplified ALK (NB-1), and those carrying the activating ALK F1174L mutation (Kelly), and, in cells carrying the activating R1275Q mutation (LAN-5), combination treatment decreased viable cell count.	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	198-201
29515255-5	2018	Accordingly, the combination of the ALK/MET inhibitor crizotinib and selective HDAC8 inhibitors (3-6 microM PCI-34051 or 10 microM 20a) efficiently killed neuroblastoma cell lines carrying wildtype ALK (SK-N-BE(2)-C, IMR5/75), amplified ALK (NB-1), and those carrying the activating ALK F1174L mutation (Kelly), and, in cells carrying the activating R1275Q mutation (LAN-5), combination treatment decreased viable cell count.	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	198-201
29515255-5	2018	Accordingly, the combination of the ALK/MET inhibitor crizotinib and selective HDAC8 inhibitors (3-6 microM PCI-34051 or 10 microM 20a) efficiently killed neuroblastoma cell lines carrying wildtype ALK (SK-N-BE(2)-C, IMR5/75), amplified ALK (NB-1), and those carrying the activating ALK F1174L mutation (Kelly), and, in cells carrying the activating R1275Q mutation (LAN-5), combination treatment decreased viable cell count.	Crizotinib	54-64	CD177 molecule	Homo sapiens	242-246
29515255-5	2018	Accordingly, the combination of the ALK/MET inhibitor crizotinib and selective HDAC8 inhibitors (3-6 microM PCI-34051 or 10 microM 20a) efficiently killed neuroblastoma cell lines carrying wildtype ALK (SK-N-BE(2)-C, IMR5/75), amplified ALK (NB-1), and those carrying the activating ALK F1174L mutation (Kelly), and, in cells carrying the activating R1275Q mutation (LAN-5), combination treatment decreased viable cell count.	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	198-201
29515255-6	2018	The effective dose of crizotinib in neuroblastoma cell lines ranged from 0.05 microM (ALK-amplified) to 0.8 microM (wildtype ALK).	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	86-89
29515255-6	2018	The effective dose of crizotinib in neuroblastoma cell lines ranged from 0.05 microM (ALK-amplified) to 0.8 microM (wildtype ALK).	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	125-128
30072474-0	2018	Amplification of Wild-type KRAS Imparts Resistance to Crizotinib in MET Exon 14 Mutant Non-Small Cell Lung Cancer.	Crizotinib	54-64	KRAS proto-oncogene, GTPase	Homo sapiens	27-31
30072474-0	2018	Amplification of Wild-type KRAS Imparts Resistance to Crizotinib in MET Exon 14 Mutant Non-Small Cell Lung Cancer.	Crizotinib	54-64	SAFB like transcription modulator	Homo sapiens	68-71
30072474-3	2018	In this study, we characterize acquired amplification of wild-type (WT) KRAS as a molecular mechanism behind crizotinib resistance in three cases of METex14-mutant NSCLC and propose a combination therapy to target it.	Crizotinib	109-119	KRAS proto-oncogene, GTPase	Homo sapiens	72-76
30072474-8	2018	RESULTS: KRAS amplification is a recurrent genetic event in crizotinib-resistant METex14-mutant NSCLC.	Crizotinib	60-70	KRAS proto-oncogene, GTPase	Homo sapiens	9-13
30072474-10	2018	CONCLUSIONS: Using patient-derived cell line and xenografts, we characterize the mechanism of crizotinib resistance mediated by KRAS amplification in METex14-mutant NSCLC and demonstrate the superior efficacy of the dual MET/PI3K inhibition as a therapeutic strategy addressing this resistance mechanism.	Crizotinib	94-104	KRAS proto-oncogene, GTPase	Homo sapiens	128-132
30072474-10	2018	CONCLUSIONS: Using patient-derived cell line and xenografts, we characterize the mechanism of crizotinib resistance mediated by KRAS amplification in METex14-mutant NSCLC and demonstrate the superior efficacy of the dual MET/PI3K inhibition as a therapeutic strategy addressing this resistance mechanism.	Crizotinib	94-104	SAFB like transcription modulator	Homo sapiens	150-153
30657798-1	2018	Crizotinib was approved by the US Food and Drug Administration in 2011 for the treatment of anaplastic lymphoma kinase (ALK)- or ROS1-positive non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	92-118
30657798-1	2018	Crizotinib was approved by the US Food and Drug Administration in 2011 for the treatment of anaplastic lymphoma kinase (ALK)- or ROS1-positive non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	120-123
30657798-1	2018	Crizotinib was approved by the US Food and Drug Administration in 2011 for the treatment of anaplastic lymphoma kinase (ALK)- or ROS1-positive non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	129-133
30118545-0	2018	Synthesis of deuterium-labeled crizotinib, a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK).	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	144-170
30118545-0	2018	Synthesis of deuterium-labeled crizotinib, a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK).	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	172-175
30205165-0	2018	Identification of a High-Level MET Amplification in CTCs and cfTNA of an ALK-Positive NSCLC Patient Developing Evasive Resistance to Crizotinib.	Crizotinib	133-143	ALK receptor tyrosine kinase	Homo sapiens	73-76
30593165-7	2018	As the ROS1-fusion was found by next generation sequencing, the patient received crizotinib treatment about 3 months.	Crizotinib	81-91	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	7-11
30627092-0	2018	Success of Crizotinib Combined with Whole-Brain Radiotherapy for Brain Metastases in a Patient with Anaplastic Lymphoma Kinase Rearrangement-Positive Non-Small-Cell Lung Cancer.	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	100-126
30627092-1	2018	Although crizotinib shows marked antitumor activity in anaplastic lymphoma kinase (ALK) rearrangement-positive non-small-cell lung cancer (NSCLC) patients, all treated patients ultimately develop resistance to this drug.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	55-81
30627092-1	2018	Although crizotinib shows marked antitumor activity in anaplastic lymphoma kinase (ALK) rearrangement-positive non-small-cell lung cancer (NSCLC) patients, all treated patients ultimately develop resistance to this drug.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	83-86
30627092-2	2018	Isolated central nervous system failure without progression at extracranial sites is a common progression pattern in ALK rearrangement-positive NSCLC patients treated with crizotinib.	Crizotinib	172-182	ALK receptor tyrosine kinase	Homo sapiens	117-120
30627092-3	2018	Here, we report the success of crizotinib combined with whole-brain radiotherapy in an ALK rearrangement-positive NSCLC patient who developed leptomeningeal carcinomatosis and progression of multiple brain metastases.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	87-90
30459281-5	2018	However, monotherapy with the ALK inhibitor crizotinib has been less encouraging in neuroblastoma patients with ALK alterations, raising the question of whether combinatorial therapy would be more effective.	Crizotinib	44-54	ALK receptor tyrosine kinase	Homo sapiens	30-33
30459281-5	2018	However, monotherapy with the ALK inhibitor crizotinib has been less encouraging in neuroblastoma patients with ALK alterations, raising the question of whether combinatorial therapy would be more effective.	Crizotinib	44-54	ALK receptor tyrosine kinase	Homo sapiens	112-115
30459283-3	2018	Here, we performed quantitative mass spectrometry-based proteomics on neuroblastoma cells treated with one of three clinically relevant ALK TKIs (crizotinib, LDK378, or lorlatinib) or an experimentally used ALK TKI (TAE684) to unravel aberrant ALK signaling pathways.	Crizotinib	146-156	ALK tyrosine kinase receptor	Cricetulus griseus	136-139
30228011-11	2018	Ceritinib is an effective agent for both crizotinib-naive and crizotinib-pretreated patients with locally advanced or metastatic ALK-rearranged NSCLC.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	129-132
30010043-0	2018	CUX1-ALK, a Novel ALK Rearrangement That Responds to Crizotinib in Non-Small Cell Lung Cancer.	Crizotinib	53-63	cut like homeobox 1	Homo sapiens	0-4
30381567-0	2018	Concomitant expression of exon 19 mutation epidermal growth factor receptor and anaplastic lymphoma kinase gene rearrangement in metastatic adenocarcinoma lung responsive to crizotinib.	Crizotinib	174-184	epidermal growth factor receptor	Homo sapiens	43-75
30508887-3	2018	Recently, Crizotinib, the antagonist of anaplastic lymphoma kinase (ALK), has been widely used in ALK-rearranged lung cancer treatment.	Crizotinib	10-20	ALK receptor tyrosine kinase	Homo sapiens	40-66
30368411-0	2018	Identification of EML4-ALK Rearrangement and MET Exon 14 R988C Mutation in a Patient with High-Grade Neuroendocrine Lung Carcinoma Who Experienced a Lazarus Response to Crizotinib.	Crizotinib	169-179	EMAP like 4	Homo sapiens	18-22
30013190-7	2018	Furthermore, the BTK inhibitor ibrutinib can effectively inhibit the growth of neuroblastoma xenograft in nude mice, and the combination of ibrutinib and the ALK inhibitor crizotinib further enhances the inhibition.	Crizotinib	172-182	anaplastic lymphoma kinase	Mus musculus	158-161
30333869-10	2018	Application of HGF activated MET and the downstream AKT signaling pathways, decreased apoptotic events and restored cell proliferation, which were reversed by MET inhibition via crizotinib or siRNA knockdown.	Crizotinib	178-188	hepatocyte growth factor	Homo sapiens	15-18
30333869-10	2018	Application of HGF activated MET and the downstream AKT signaling pathways, decreased apoptotic events and restored cell proliferation, which were reversed by MET inhibition via crizotinib or siRNA knockdown.	Crizotinib	178-188	AKT serine/threonine kinase 1	Homo sapiens	52-55
30340555-1	2018	BACKGROUND: Ceritinib demonstrated a statistically significant effect on the progression-free survival versus chemotherapy in patients with advanced anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC) as the first therapy or after previous treatment with crizotinib and one or two prior chemotherapy regimens in global phase 3 studies.	Crizotinib	288-298	ALK receptor tyrosine kinase	Homo sapiens	177-180
30368411-0	2018	Identification of EML4-ALK Rearrangement and MET Exon 14 R988C Mutation in a Patient with High-Grade Neuroendocrine Lung Carcinoma Who Experienced a Lazarus Response to Crizotinib.	Crizotinib	169-179	ALK receptor tyrosine kinase	Homo sapiens	23-26
30368417-0	2018	Combination of Crizotinib and Osimertinib or Erlotinib Might Overcome MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitor in EGFR-Mutated Adenocarcinoma.	Crizotinib	15-25	epidermal growth factor receptor	Homo sapiens	97-101
30368417-0	2018	Combination of Crizotinib and Osimertinib or Erlotinib Might Overcome MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitor in EGFR-Mutated Adenocarcinoma.	Crizotinib	15-25	epidermal growth factor receptor	Homo sapiens	131-135
30368418-0	2018	A Novel EML6-ALK FBXO11-ALK Double Fusion Variant in Lung Adenocarcinoma and Response to Crizotinib.	Crizotinib	89-99	EMAP like 6	Homo sapiens	8-12
30368418-0	2018	A Novel EML6-ALK FBXO11-ALK Double Fusion Variant in Lung Adenocarcinoma and Response to Crizotinib.	Crizotinib	89-99	ALK receptor tyrosine kinase	Homo sapiens	13-16
30368418-0	2018	A Novel EML6-ALK FBXO11-ALK Double Fusion Variant in Lung Adenocarcinoma and Response to Crizotinib.	Crizotinib	89-99	F-box protein 11	Homo sapiens	17-23
30368418-0	2018	A Novel EML6-ALK FBXO11-ALK Double Fusion Variant in Lung Adenocarcinoma and Response to Crizotinib.	Crizotinib	89-99	ALK receptor tyrosine kinase	Homo sapiens	24-27
30142403-0	2018	Bosniak Category III Renal Cysts Caused by Crizotinib in an Anaplastic Lymphoma Kinase Gene-Rearranged Non-Small Cell Lung Cancer Patient.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	60-86
30142403-2	2018	Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor used to treat ALK gene-rearranged non-small cell lung cancer and reported to be associated with complex renal cyst formation.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	17-43
30142403-2	2018	Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor used to treat ALK gene-rearranged non-small cell lung cancer and reported to be associated with complex renal cyst formation.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	45-48
30142403-2	2018	Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor used to treat ALK gene-rearranged non-small cell lung cancer and reported to be associated with complex renal cyst formation.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	74-77
30142403-3	2018	We herein report a case of Bosniak category III renal cysts occurred in a crizotinib-treated ALK gene-rearranged non-small cell lung cancer patients.	Crizotinib	74-84	ALK receptor tyrosine kinase	Homo sapiens	93-96
30508887-3	2018	Recently, Crizotinib, the antagonist of anaplastic lymphoma kinase (ALK), has been widely used in ALK-rearranged lung cancer treatment.	Crizotinib	10-20	ALK receptor tyrosine kinase	Homo sapiens	68-71
30508887-3	2018	Recently, Crizotinib, the antagonist of anaplastic lymphoma kinase (ALK), has been widely used in ALK-rearranged lung cancer treatment.	Crizotinib	10-20	ALK receptor tyrosine kinase	Homo sapiens	98-101
30508887-15	2018	LESSONS: Despite the dramatic benefit of crizotinib for patients with ALK rearrangement, crizotinib-induced severe rash needs to be dealt with caution.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	70-73
30443294-9	2018	Oral crizotinib, an ROS1 inhibitor, was administered at a dose of 250 mg twice daily.	Crizotinib	5-15	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	20-24
30410351-0	2018	Crizotinib presented with promising efficacy but for concomitant mutation in next-generation sequencing-identified ROS1-rearranged non-small-cell lung cancer.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	115-119
30410351-10	2018	Among 22 patients with ROS1-rearranged NSCLC, 20 patients were diagnosed at stage IV, and 19 patients received crizotinib treatment.	Crizotinib	111-121	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	23-27
30410351-15	2018	Conclusion: Crizotinib is highly effective in NGS-identified ROS1-rearranged advanced NSCLC in real-word clinical practice, and the data are consistent with previous clinical trials applying fluorescence in situ hybridization/real-time PCR for ROS1 companion diagnosis.	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	61-65
30410351-15	2018	Conclusion: Crizotinib is highly effective in NGS-identified ROS1-rearranged advanced NSCLC in real-word clinical practice, and the data are consistent with previous clinical trials applying fluorescence in situ hybridization/real-time PCR for ROS1 companion diagnosis.	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	244-248
30410351-16	2018	Concomitant mutations may not be rare and may deteriorate the PFS of crizotinib in patients with ROS1-rearranged NSCLC.	Crizotinib	69-79	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	97-101
30053332-0	2018	Combined effect of cabozantinib and gefitinib in crizotinib-resistant lung tumors harboring ROS1 fusions.	Crizotinib	49-59	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	92-96
30053332-1	2018	The ROS1 tyrosine kinase inhibitor (TKI) crizotinib has shown dramatic effects in patients with non-small cell lung cancer (NSCLC) harboring ROS1 fusion genes.	Crizotinib	41-51	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	4-8
30053332-1	2018	The ROS1 tyrosine kinase inhibitor (TKI) crizotinib has shown dramatic effects in patients with non-small cell lung cancer (NSCLC) harboring ROS1 fusion genes.	Crizotinib	41-51	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	141-145
30053332-8	2018	Recombinant HB-EGF or EGF rendered HCC78 cells or ABC-20 cells resistant to crizotinib.	Crizotinib	76-86	heparin binding EGF like growth factor	Homo sapiens	12-18
30053332-8	2018	Recombinant HB-EGF or EGF rendered HCC78 cells or ABC-20 cells resistant to crizotinib.	Crizotinib	76-86	ATP binding cassette subfamily B member 1	Homo sapiens	50-56
30053332-13	2018	The results of this study indicated that HB-EGF/EGFR and AXL play roles in crizotinib resistance in lung cancers harboring ROS1 fusions.	Crizotinib	75-85	heparin binding EGF like growth factor	Homo sapiens	41-47
30053332-13	2018	The results of this study indicated that HB-EGF/EGFR and AXL play roles in crizotinib resistance in lung cancers harboring ROS1 fusions.	Crizotinib	75-85	epidermal growth factor receptor	Homo sapiens	48-52
30053332-13	2018	The results of this study indicated that HB-EGF/EGFR and AXL play roles in crizotinib resistance in lung cancers harboring ROS1 fusions.	Crizotinib	75-85	AXL receptor tyrosine kinase	Homo sapiens	57-60
30053332-13	2018	The results of this study indicated that HB-EGF/EGFR and AXL play roles in crizotinib resistance in lung cancers harboring ROS1 fusions.	Crizotinib	75-85	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	123-127
30230699-5	2018	RESULTS: Compared with chemotherapy, ALK inhibitors significantly prolonged PFS [hazard ratio (HR) and 95% confidence interval (CI): alectinib, 0.50 (0.43-0.58); ceritinib, 0.75 (0.69-0.83); crizotinib, 0.71 (0.66-0.76)].	Crizotinib	191-201	ALK receptor tyrosine kinase	Homo sapiens	37-40
30230699-6	2018	The ORRs were significantly higher for ALK inhibitors than for chemotherapy [odds ratio (OR) and corresponding 95% CI: alectinib, 11.69 (4.29-36.56); ceritinib, 7.85 (3.44-19.27); crizotinib, 6.04 (3.33-11.71)].	Crizotinib	180-190	ALK receptor tyrosine kinase	Homo sapiens	39-42
30230699-7	2018	The discontinuation rates were lower for ALK inhibitors than for chemotherapy [OR and corresponding 95% CI: alectinib, 0.42 (0.12-1.36); ceritinib, 0.52 (0.20-1.35); crizotinib, 0.70 (0.30-1.62)].	Crizotinib	166-176	ALK receptor tyrosine kinase	Homo sapiens	41-44
30464681-2	2018	In 2015, Canadian thoracic oncology specialists published a consensus guideline about the identification and treatment of ALK-positive patients, recommending use of the alk inhibitor crizotinib in the first line.	Crizotinib	183-193	ALK receptor tyrosine kinase	Homo sapiens	122-125
30352060-1	2018	INTRODUCTION: Anaplastic lymphoma kinase (ALK) rearrangement gene testing is used increasingly to identify patients with advanced non-small-cell lung cancer (NSCLC) who are most likely to benefit from crizotinib.	Crizotinib	201-211	ALK receptor tyrosine kinase	Homo sapiens	14-40
30352060-1	2018	INTRODUCTION: Anaplastic lymphoma kinase (ALK) rearrangement gene testing is used increasingly to identify patients with advanced non-small-cell lung cancer (NSCLC) who are most likely to benefit from crizotinib.	Crizotinib	201-211	ALK receptor tyrosine kinase	Homo sapiens	42-45
29876933-0	2018	Activation of MET signaling by HDAC6 offers a rationale for a novel ricolinostat and crizotinib combinatorial therapeutic strategy in diffuse large B-cell lymphoma.	Crizotinib	85-95	histone deacetylase 6	Homo sapiens	31-36
29935304-2	2018	Brigatinib, another second-generation ALK inhibitor, has shown substantial activity in patients with crizotinib-refractory ALK-positive NSCLC; however, its activity in the alectinib-refractory setting is unknown.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	123-126
29966800-0	2018	Results of PROFILE 1029, a Phase III Comparison of First-Line Crizotinib versus Chemotherapy in East Asian Patients with ALK-Positive Advanced Non-Small Cell Lung Cancer.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	121-124
29966800-1	2018	INTRODUCTION: The phase III randomized PROFILE 1014 study demonstrated superiority of crizotinib to first-line chemotherapy in prolonging progression-free survival (PFS) in previously untreated patients with ALK receptor tyrosine kinase gene (ALK)-positive advanced nonsquamous NSCLC.	Crizotinib	86-96	ALK receptor tyrosine kinase	Homo sapiens	208-211
29966800-1	2018	INTRODUCTION: The phase III randomized PROFILE 1014 study demonstrated superiority of crizotinib to first-line chemotherapy in prolonging progression-free survival (PFS) in previously untreated patients with ALK receptor tyrosine kinase gene (ALK)-positive advanced nonsquamous NSCLC.	Crizotinib	86-96	ALK receptor tyrosine kinase	Homo sapiens	243-246
29966800-11	2018	CONCLUSIONS: First-line crizotinib significantly improved PFS, objective response rate, and patient-reported outcomes compared with standard platinum-based chemotherapy in East Asian patients with ALK-positive advanced NSCLC, which is similar to the results from PROFILE 1014.	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	197-200
29573824-0	2018	Heterogeneous MET gene copy number and EGFR mutation elicit discordant responses to crizotinib between primary and metastatic lesions in erlotinib-resistant lung adenocarcinoma.	Crizotinib	84-94	epidermal growth factor receptor	Homo sapiens	39-43
30268451-0	2018	Crizotinib treatment for patients with EGFR mutation positive NSCLC that acquire cMET amplification after EGFR TKI therapy results in short-lived and heterogeneous responses.	Crizotinib	0-10	epidermal growth factor receptor	Homo sapiens	39-43
30268451-0	2018	Crizotinib treatment for patients with EGFR mutation positive NSCLC that acquire cMET amplification after EGFR TKI therapy results in short-lived and heterogeneous responses.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	81-85
30268451-0	2018	Crizotinib treatment for patients with EGFR mutation positive NSCLC that acquire cMET amplification after EGFR TKI therapy results in short-lived and heterogeneous responses.	Crizotinib	0-10	epidermal growth factor receptor	Homo sapiens	106-110
30268451-2	2018	Crizotinib, a dual ALK and cMET inhibitor, can induce responses in patients with EGFR mutation positive non-small cell lung cancer (NSCLC) that acquire cMET amplification after EGFR TKI treatment.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	19-22
30268451-2	2018	Crizotinib, a dual ALK and cMET inhibitor, can induce responses in patients with EGFR mutation positive non-small cell lung cancer (NSCLC) that acquire cMET amplification after EGFR TKI treatment.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	27-31
30268451-2	2018	Crizotinib, a dual ALK and cMET inhibitor, can induce responses in patients with EGFR mutation positive non-small cell lung cancer (NSCLC) that acquire cMET amplification after EGFR TKI treatment.	Crizotinib	0-10	epidermal growth factor receptor	Homo sapiens	81-85
30268451-2	2018	Crizotinib, a dual ALK and cMET inhibitor, can induce responses in patients with EGFR mutation positive non-small cell lung cancer (NSCLC) that acquire cMET amplification after EGFR TKI treatment.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	152-156
30268451-2	2018	Crizotinib, a dual ALK and cMET inhibitor, can induce responses in patients with EGFR mutation positive non-small cell lung cancer (NSCLC) that acquire cMET amplification after EGFR TKI treatment.	Crizotinib	0-10	epidermal growth factor receptor	Homo sapiens	177-181
30268451-4	2018	Here, we report on the clinical outcome of a series of patients with cMET-driven resistance to EGFR TKIs, treated with crizotinib.	Crizotinib	119-129	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	69-73
30268451-4	2018	Here, we report on the clinical outcome of a series of patients with cMET-driven resistance to EGFR TKIs, treated with crizotinib.	Crizotinib	119-129	epidermal growth factor receptor	Homo sapiens	95-99
30268451-14	2018	CONCLUSION: Crizotinib treatment for patients with EGFR mutation positive NSCLC that acquire cMET amplification after EGFR TKI treatment results in short-lived and often heterogeneous responses, possibly due to subclonality of cMET-driven resistance and co-occurrence of other EGFR TKI resistance mechanisms.	Crizotinib	12-22	epidermal growth factor receptor	Homo sapiens	51-55
30268451-14	2018	CONCLUSION: Crizotinib treatment for patients with EGFR mutation positive NSCLC that acquire cMET amplification after EGFR TKI treatment results in short-lived and often heterogeneous responses, possibly due to subclonality of cMET-driven resistance and co-occurrence of other EGFR TKI resistance mechanisms.	Crizotinib	12-22	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	93-97
30268451-14	2018	CONCLUSION: Crizotinib treatment for patients with EGFR mutation positive NSCLC that acquire cMET amplification after EGFR TKI treatment results in short-lived and often heterogeneous responses, possibly due to subclonality of cMET-driven resistance and co-occurrence of other EGFR TKI resistance mechanisms.	Crizotinib	12-22	epidermal growth factor receptor	Homo sapiens	118-122
30268451-14	2018	CONCLUSION: Crizotinib treatment for patients with EGFR mutation positive NSCLC that acquire cMET amplification after EGFR TKI treatment results in short-lived and often heterogeneous responses, possibly due to subclonality of cMET-driven resistance and co-occurrence of other EGFR TKI resistance mechanisms.	Crizotinib	12-22	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	227-231
30268451-14	2018	CONCLUSION: Crizotinib treatment for patients with EGFR mutation positive NSCLC that acquire cMET amplification after EGFR TKI treatment results in short-lived and often heterogeneous responses, possibly due to subclonality of cMET-driven resistance and co-occurrence of other EGFR TKI resistance mechanisms.	Crizotinib	12-22	epidermal growth factor receptor	Homo sapiens	118-122
30218431-0	2018	Characteristics and Response to Crizotinib in ALK-Rearranged, Advanced Non-Adenocarcinoma, Non-Small Cell Lung Cancer (NA-NSCLC) Patients: a Retrospective Study and Literature Review.	Crizotinib	32-42	ALK receptor tyrosine kinase	Homo sapiens	46-49
30218431-6	2018	The effectiveness of crizotinib in ALK-positive patients was retrospectively analyzed.	Crizotinib	21-31	ALK receptor tyrosine kinase	Homo sapiens	35-38
30218431-15	2018	Crizotinib provides an option for the treatment of NA-NSCLC patients who have an ALK rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	81-84
30212301-0	2018	Should Crizotinib Take It All in ROS1-Positive Non-Small-Cell Lung Cancer?	Crizotinib	7-17	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	33-37
29768119-1	2018	Purpose In patients with crizotinib-treated, anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC), initial disease progression often occurs in the CNS.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	45-76
29768119-1	2018	Purpose In patients with crizotinib-treated, anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC), initial disease progression often occurs in the CNS.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	79-82
29768119-1	2018	Purpose In patients with crizotinib-treated, anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC), initial disease progression often occurs in the CNS.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	123-126
30103190-0	2018	Identification of crizotinib derivatives as potent SHIP2 inhibitors for the treatment of Alzheimer"s disease.	Crizotinib	18-28	inositol polyphosphate phosphatase-like 1	Mus musculus	51-56
30103190-3	2018	In the present study, we have developed novel, potent SHIP2 inhibitors by extensive structural elaboration of crizotinib discovered from a high-throughput screening.	Crizotinib	110-120	inositol polyphosphate phosphatase-like 1	Mus musculus	54-59
30464681-2	2018	In 2015, Canadian thoracic oncology specialists published a consensus guideline about the identification and treatment of ALK-positive patients, recommending use of the alk inhibitor crizotinib in the first line.	Crizotinib	183-193	ALK receptor tyrosine kinase	Homo sapiens	169-172
30464681-7	2018	Improved responses in brain metastases were observed for all second- and next/third-generation alk tyrosine kinase inhibitors in patients progressing on crizotinib.	Crizotinib	153-163	ALK receptor tyrosine kinase	Homo sapiens	95-98
30194140-4	2018	Herein is a review of the efficacy, indications, and degree of CNS penetration for the ALK-targeting agents crizotinib, ceretinib, alectinib, brigatinib, and lorlatinib, as well as a summary of ongoing clinical trials comparing these drugs.	Crizotinib	108-118	ALK receptor tyrosine kinase	Homo sapiens	87-90
30083883-0	2018	A lung squamous carcinoma patient with ROS1 rearrangement sensitive to crizotinib.	Crizotinib	71-81	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	39-43
30083883-4	2018	An 84-year-old Chinese woman with a about 6.6 cm mass in the right middle lobe and right pleural effusion, enlarged mediastinal and hilar lymph nodes was diagnosed with stage IIIB lung squamous cell carcinoma harboring ROS1 rearrangement is highly sensitive to crizotinib in the first treatment setting.	Crizotinib	261-271	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	219-223
30083883-5	2018	This is the first time to report lung squamous carcinoma patient with ROS1 rearrangement sensitive to crizotinib.	Crizotinib	102-112	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	70-74
30021798-5	2018	Anti-miR-205 transduction reverted crizotinib resistance in vivo, while miR-205 over-expression rendered wt cells refractory to TKI treatment.	Crizotinib	35-45	microRNA 205	Homo sapiens	5-12
30251885-3	2018	Areas covered: The first-generation ALK inhibitor is crizotinib, initially used in Europe as second-line treatment for ALK-positive metastatic NSCLC patients, then approved as the standard first-line (already approved in the USA as front-line therapy).	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	36-39
30251885-3	2018	Areas covered: The first-generation ALK inhibitor is crizotinib, initially used in Europe as second-line treatment for ALK-positive metastatic NSCLC patients, then approved as the standard first-line (already approved in the USA as front-line therapy).	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	119-122
28787324-4	2018	Following classification of the tumor as EIMS, the patient began treatment with an ALK inhibitor (crizotinib), which led to disease improvement within weeks of administration.	Crizotinib	98-108	ALK receptor tyrosine kinase	Homo sapiens	83-86
28893136-2	2018	The anaplastic lymphoma kinase inhibitor crizotinib has been granted approval for the treatment of patients with ROS1 positive metastatic non-small-cell lung cancer by the Food and Drug Administration on 2016.	Crizotinib	41-51	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	113-117
29663378-5	2018	Furthermore, treatment of human SCS calvarial cells with the tyrosine kinase chemical inhibitor, Crizotinib, resulted in reduced C-ROS-1 activity and the osteogenic potential of human SCS calvarial cells with minor effects on cell viability or proliferation.	Crizotinib	97-107	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	129-136
29663378-6	2018	Cultured human SCS calvarial cells treated with Crizotinib exhibited a dose-dependent decrease in alkaline phosphatase activity and mineral deposition, with an associated decrease in expression levels of Runt-related transcription factor 2 and OSTEOPONTIN, with reduced PI3K/Akt signalling in vitro.	Crizotinib	48-58	RUNX family transcription factor 2	Homo sapiens	204-239
29663378-6	2018	Cultured human SCS calvarial cells treated with Crizotinib exhibited a dose-dependent decrease in alkaline phosphatase activity and mineral deposition, with an associated decrease in expression levels of Runt-related transcription factor 2 and OSTEOPONTIN, with reduced PI3K/Akt signalling in vitro.	Crizotinib	48-58	secreted phosphoprotein 1	Homo sapiens	244-255
29663378-6	2018	Cultured human SCS calvarial cells treated with Crizotinib exhibited a dose-dependent decrease in alkaline phosphatase activity and mineral deposition, with an associated decrease in expression levels of Runt-related transcription factor 2 and OSTEOPONTIN, with reduced PI3K/Akt signalling in vitro.	Crizotinib	48-58	AKT serine/threonine kinase 1	Homo sapiens	275-278
29663378-7	2018	Furthermore, Crizotinib treatment resulted in reduced BMP-2 mediated bone formation potential of whole Twist-1del/+ mutant mouse calvaria organotypic cultures.	Crizotinib	13-23	bone morphogenetic protein 2	Mus musculus	54-59
29663378-10	2018	Therefore, targeting C-ROS-1 with a pharmacological agent, such as Crizotinib, may serve as a novel therapeutic strategy to alleviate craniosynostosis associated with aberrant TWIST-1 function.	Crizotinib	67-77	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	21-28
29663378-10	2018	Therefore, targeting C-ROS-1 with a pharmacological agent, such as Crizotinib, may serve as a novel therapeutic strategy to alleviate craniosynostosis associated with aberrant TWIST-1 function.	Crizotinib	67-77	twist family bHLH transcription factor 1	Homo sapiens	176-183
29588546-9	2018	Finally, pharmacological inhibition of RORC as single treatment leads to cell death in ALCL cell lines and, in combination with the ALK inhibitor crizotinib, enforces death induction in ALK+ ALCL.	Crizotinib	146-156	ALK receptor tyrosine kinase	Homo sapiens	132-135
29588546-9	2018	Finally, pharmacological inhibition of RORC as single treatment leads to cell death in ALCL cell lines and, in combination with the ALK inhibitor crizotinib, enforces death induction in ALK+ ALCL.	Crizotinib	146-156	ALK receptor tyrosine kinase	Homo sapiens	186-189
30089600-0	2018	Next generation sequencing reveals a novel ALK G1128A mutation resistant to crizotinib in an ALK-Rearranged NSCLC patient.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	43-46
30089600-0	2018	Next generation sequencing reveals a novel ALK G1128A mutation resistant to crizotinib in an ALK-Rearranged NSCLC patient.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	93-96
30089600-1	2018	OBJECTIVE: Acquired secondary mutations in the anaplastic lymphoma kinase (ALK) gene have been identified in ALK-rearranged non-small cell lung cancer (NSCLC) patients who are resistant to treatment with the ALK inhibitor crizotinib.	Crizotinib	222-232	ALK receptor tyrosine kinase	Homo sapiens	47-73
30089600-1	2018	OBJECTIVE: Acquired secondary mutations in the anaplastic lymphoma kinase (ALK) gene have been identified in ALK-rearranged non-small cell lung cancer (NSCLC) patients who are resistant to treatment with the ALK inhibitor crizotinib.	Crizotinib	222-232	ALK receptor tyrosine kinase	Homo sapiens	75-78
30089600-1	2018	OBJECTIVE: Acquired secondary mutations in the anaplastic lymphoma kinase (ALK) gene have been identified in ALK-rearranged non-small cell lung cancer (NSCLC) patients who are resistant to treatment with the ALK inhibitor crizotinib.	Crizotinib	222-232	ALK receptor tyrosine kinase	Homo sapiens	109-112
30089600-1	2018	OBJECTIVE: Acquired secondary mutations in the anaplastic lymphoma kinase (ALK) gene have been identified in ALK-rearranged non-small cell lung cancer (NSCLC) patients who are resistant to treatment with the ALK inhibitor crizotinib.	Crizotinib	222-232	ALK receptor tyrosine kinase	Homo sapiens	109-112
30089600-4	2018	RESULTS: We identified a novel acquired NSCLC ALK G1128A mutation in the ALK + NSCLC patient who progressed on crizotinib after a short partial response to the drug.	Crizotinib	111-121	ALK receptor tyrosine kinase	Homo sapiens	46-49
30089600-4	2018	RESULTS: We identified a novel acquired NSCLC ALK G1128A mutation in the ALK + NSCLC patient who progressed on crizotinib after a short partial response to the drug.	Crizotinib	111-121	ALK receptor tyrosine kinase	Homo sapiens	73-76
30089600-6	2018	As a gain-of-function mutation, ALK G1128A increases kinase activity and transformation ability, perhaps conferring resistance to crizotinib.	Crizotinib	130-140	ALK receptor tyrosine kinase	Homo sapiens	32-35
30089600-7	2018	CONCLUSIONS: This case further illustrates the importance of comprehensive genomic profiling of resistant tumors for tailoring treatment decisions after disease progression on crizotinib in ALK + NSCLC in the era of rapidly developing new-generation ALK inhibitors and other therapeutic strategies.	Crizotinib	176-186	ALK receptor tyrosine kinase	Homo sapiens	190-193
29978950-0	2018	Heterogeneous responses and resistant mechanisms to crizotinib in ALK-positive advanced non-small cell lung cancer.	Crizotinib	52-62	ALK receptor tyrosine kinase	Homo sapiens	66-69
30134855-0	2018	A primary undifferentiated pleomorphic sarcoma of the lumbosacral region harboring a LMNA-NTRK1 gene fusion with durable clinical response to crizotinib: a case report.	Crizotinib	142-152	lamin A/C	Homo sapiens	85-89
30134855-0	2018	A primary undifferentiated pleomorphic sarcoma of the lumbosacral region harboring a LMNA-NTRK1 gene fusion with durable clinical response to crizotinib: a case report.	Crizotinib	142-152	neurotrophic receptor tyrosine kinase 1	Homo sapiens	90-95
30134855-7	2018	The patient then began treatment with crizotinib at an oral dose of 450 mg per day, based on the detection of a LMNA-NTRK1 fusion gene in the tumor by next-generation sequencing.	Crizotinib	38-48	lamin A/C	Homo sapiens	112-116
30134855-7	2018	The patient then began treatment with crizotinib at an oral dose of 450 mg per day, based on the detection of a LMNA-NTRK1 fusion gene in the tumor by next-generation sequencing.	Crizotinib	38-48	neurotrophic receptor tyrosine kinase 1	Homo sapiens	117-122
30134855-9	2018	CONCLUSIONS: The LMNA-NTRK1 fusion was likely the molecular driver of tumorigenesis and metastasis in this patient, and the observed effectiveness of crizotinib treatment provides clinical validation of this molecular target.	Crizotinib	150-160	lamin A/C	Homo sapiens	17-21
30134855-9	2018	CONCLUSIONS: The LMNA-NTRK1 fusion was likely the molecular driver of tumorigenesis and metastasis in this patient, and the observed effectiveness of crizotinib treatment provides clinical validation of this molecular target.	Crizotinib	150-160	neurotrophic receptor tyrosine kinase 1	Homo sapiens	22-27
30154667-5	2018	One case of atypical carcinoid tumor and 1 case of large cell NEC (LCNEC) achieved response to ALK inhibitor (crizotinib) treatment.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	95-98
30147334-6	2018	The studies of crizotinib in the treatment of patients with ASC are very limited.	Crizotinib	15-25	PYD and CARD domain containing	Homo sapiens	60-63
30140094-1	2018	Crizotinib is an inhibitor of multiple tyrosine kinases, including the anaplastic lymphoma kinase (ALK).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	71-97
30140094-1	2018	Crizotinib is an inhibitor of multiple tyrosine kinases, including the anaplastic lymphoma kinase (ALK).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	99-102
30140094-2	2018	Responses to crizotinib have also been reported in patients with ALK-positive anaplastic large-cell lymphoma (ALCL) and solid tumors with ALK-mutation, including neuroblastoma.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	65-68
30140094-2	2018	Responses to crizotinib have also been reported in patients with ALK-positive anaplastic large-cell lymphoma (ALCL) and solid tumors with ALK-mutation, including neuroblastoma.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	138-141
30140094-5	2018	The objectives of this trial are to evaluate the tolerability and safety of crizotinib in Japanese patients with recurrent/refractory ALK-positive ALCL or neuroblastoma (phase I) and its efficacy in recurrent/refractory ALK-positive ALCL (phase II).	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	134-137
30140094-5	2018	The objectives of this trial are to evaluate the tolerability and safety of crizotinib in Japanese patients with recurrent/refractory ALK-positive ALCL or neuroblastoma (phase I) and its efficacy in recurrent/refractory ALK-positive ALCL (phase II).	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	220-223
29803091-0	2018	Crizotinib and erlotinib inhibits growth of c-Met+/EGFRvIII+ primary human glioblastoma xenografts.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	44-49
29803091-11	2018	RESULTS: Crizotinib (c-Met pathway inhibitor) and Erlotinib (EGFR pathway inhibitor) in combination significantly inhibited tumor growth, phospho-EGFRvIII, phospho-Met, phospho-AKT, phospho-MAPK, and neurosphere growth in Mayo 39 and Mayo 59 primary GBM subcutaneous xenografts.	Crizotinib	9-19	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	21-26
29803964-5	2018	The created profile is analyzed at structural, energetic and dynamic levels and, consequently, totally 18 promising UKII pairs with high theoretical affinity are derived, from which the noncognate inhibitors Cabozantinib, Regorafenib and Crizotinib are selected to test their cytotoxic effects on human epithelial colorectal adenocarcinoma Caco-2 cell line and inhibition activity against the recombinant protein of human p38alpha kinase domain.	Crizotinib	238-248	mitogen-activated protein kinase 14	Homo sapiens	422-430
29907598-2	2018	Although mutations in ALK are heavily implicated in childhood neuroblastoma, response to the ALK TKI crizotinib has been disappointing.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	93-96
30068733-8	2018	EML4-ALK fusions are driver events in 2%-5% of non-small-cell lung cancers; crizotinib is an approved targeted therapy for these patients.	Crizotinib	76-86	EMAP like 4	Homo sapiens	0-4
30068733-8	2018	EML4-ALK fusions are driver events in 2%-5% of non-small-cell lung cancers; crizotinib is an approved targeted therapy for these patients.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	5-8
29451020-4	2018	An ALK inhibitor (crizotinib, ceritinib and alectinib) is the preferred therapeutic approach to those advanced ALK fusion variant-positive NSCLC patients.	Crizotinib	18-28	ALK receptor tyrosine kinase	Homo sapiens	3-6
30010763-8	2018	As a continuous variable, higher percentages of ALK-positive cells were estimated to be associated with larger differences in objective response and PFS between crizotinib and chemotherapy; however, tests for interaction between treatment and percentage of ALK-positive cells were not significant (objective response, P = 0.054; PFS, P = 0.17).	Crizotinib	161-171	ALK receptor tyrosine kinase	Homo sapiens	48-51
30010763-9	2018	Conclusions: Patients with ALK-positive NSCLC benefit from treatment with crizotinib across the full range of percentage of ALK-positive cells, supporting the clinical utility of the 15% cut-off.	Crizotinib	74-84	ALK receptor tyrosine kinase	Homo sapiens	27-30
30010763-9	2018	Conclusions: Patients with ALK-positive NSCLC benefit from treatment with crizotinib across the full range of percentage of ALK-positive cells, supporting the clinical utility of the 15% cut-off.	Crizotinib	74-84	ALK receptor tyrosine kinase	Homo sapiens	124-127
29536761-2	2018	Alectinib, a next generation ALK inhibitor, recently demonstrated, in two separate Phase III trials, superior efficacy to crizotinib, the first ALK inhibitor to demonstrate clinical efficacy in ALK-positive NSCLC patients.	Crizotinib	122-132	ALK receptor tyrosine kinase	Homo sapiens	144-147
29536761-2	2018	Alectinib, a next generation ALK inhibitor, recently demonstrated, in two separate Phase III trials, superior efficacy to crizotinib, the first ALK inhibitor to demonstrate clinical efficacy in ALK-positive NSCLC patients.	Crizotinib	122-132	ALK receptor tyrosine kinase	Homo sapiens	144-147
29768118-0	2018	Final Overall Survival Analysis From a Study Comparing First-Line Crizotinib Versus Chemotherapy in ALK-Mutation-Positive Non-Small-Cell Lung Cancer.	Crizotinib	66-76	ALK receptor tyrosine kinase	Homo sapiens	100-103
29768118-1	2018	Purpose The phase III PROFILE 1014 trial compared crizotinib with chemotherapy as first-line treatment in patients with anaplastic lymphoma kinase (ALK) -positive advanced nonsquamous non-small-cell lung cancer.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	120-146
29768118-1	2018	Purpose The phase III PROFILE 1014 trial compared crizotinib with chemotherapy as first-line treatment in patients with anaplastic lymphoma kinase (ALK) -positive advanced nonsquamous non-small-cell lung cancer.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	148-151
29768118-12	2018	The longest OS was observed in crizotinib-treated patients who received a subsequent ALK tyrosine kinase inhibitor.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	85-88
29768118-14	2018	Conclusion The final analysis of the PROFILE 1014 study provides a new benchmark for OS in patients with ALK-rearranged non-small-cell lung cancer and highlights the benefit of crizotinib for prolonging survival in this patient population.	Crizotinib	177-187	ALK receptor tyrosine kinase	Homo sapiens	105-108
30049378-0	2018	Clinical Activity of Crizotinib in Lung Adenocarcinoma Harboring a Rare ZCCHC8-ROS1 Fusion.	Crizotinib	21-31	zinc finger CCHC-type containing 8	Homo sapiens	72-78
30049378-0	2018	Clinical Activity of Crizotinib in Lung Adenocarcinoma Harboring a Rare ZCCHC8-ROS1 Fusion.	Crizotinib	21-31	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	79-83
30075548-1	2018	RATIONALE: Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), a distinct molecular entity, is highly sensitive to ALK tyrosine kinase inhibitors (TKIs) such as crizotinib or ceritinib.	Crizotinib	197-207	EMAP like 4	Homo sapiens	88-92
30075548-1	2018	RATIONALE: Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), a distinct molecular entity, is highly sensitive to ALK tyrosine kinase inhibitors (TKIs) such as crizotinib or ceritinib.	Crizotinib	197-207	ALK receptor tyrosine kinase	Homo sapiens	93-96
30075548-1	2018	RATIONALE: Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), a distinct molecular entity, is highly sensitive to ALK tyrosine kinase inhibitors (TKIs) such as crizotinib or ceritinib.	Crizotinib	197-207	ALK receptor tyrosine kinase	Homo sapiens	151-154
29697184-0	2018	Crizotinib induces apoptosis and gene expression changes in ALK+ anaplastic large cell lymphoma cell lines; brentuximab synergizes and doxorubicin antagonizes.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	60-63
29697184-12	2018	CONCLUSIONS: Our data suggest that crizotinib induces apoptosis through orderly changes in cell signaling associated with ALK inhibition.	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	122-125
30327756-0	2018	Targeting ROS1 rearrangements in non-small cell lung cancer with crizotinib and other kinase inhibitors.	Crizotinib	65-75	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	10-14
30029601-0	2018	Fatal interstitial lung disease associated with Crizotinib pathologically confirmed by percutaneous lung biopsy in a patient with ROS1-rearranged advanced non-small-cell lung cancer: a case report.	Crizotinib	48-58	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	130-134
30029601-1	2018	BACKGROUND: Crizotinib is a multi-target inhibitor approved for the treatment of advanced non-small-cell lung cancer patients with a ROS1 rearrangement.	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	133-137
30029601-4	2018	CASE PRESENTATION: We first identified and reported interstitial lung disease induced de novo by crizotinib in a 47-year-old female patient who was diagnosed with advanced lung adenocarcinoma with a ROS1 rearrangement in a malignant pleural effusion.	Crizotinib	97-107	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	199-203
29748847-0	2018	Exposure-response analysis of alectinib in crizotinib-resistant ALK-positive non-small cell lung cancer.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	64-67
29935846-0	2018	GOPC-ROS1 Rearrangement as an Acquired Resistance Mechanism to Osimertinib and Responding to Crizotinib Combined Treatments in Lung Adenocarcinoma.	Crizotinib	93-103	golgi associated PDZ and coiled-coil motif containing	Homo sapiens	0-9
29738763-2	2018	Several clinical studies have highlighted ROS1 as a promising therapeutic target because crizotinib, a multi-targeted drug against ROS1, ALK, and the MET proto-oncogene, has elicited remarkable responses in ROS1-rearrangements NSCLC.	Crizotinib	89-99	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	42-46
29738763-2	2018	Several clinical studies have highlighted ROS1 as a promising therapeutic target because crizotinib, a multi-targeted drug against ROS1, ALK, and the MET proto-oncogene, has elicited remarkable responses in ROS1-rearrangements NSCLC.	Crizotinib	89-99	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	131-135
29738763-2	2018	Several clinical studies have highlighted ROS1 as a promising therapeutic target because crizotinib, a multi-targeted drug against ROS1, ALK, and the MET proto-oncogene, has elicited remarkable responses in ROS1-rearrangements NSCLC.	Crizotinib	89-99	ALK receptor tyrosine kinase	Homo sapiens	137-140
29738763-2	2018	Several clinical studies have highlighted ROS1 as a promising therapeutic target because crizotinib, a multi-targeted drug against ROS1, ALK, and the MET proto-oncogene, has elicited remarkable responses in ROS1-rearrangements NSCLC.	Crizotinib	89-99	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	131-135
29738763-8	2018	This eventually enabled us to engraft and stably grow the cells in vivo, and subsequently evaluate various ROS1 inhibitors against HCC78xe3 cells by overexpressing crizotinib-resistant mutations in the ROS1 kinase domain including G2032R and D2033 N. We newly found that lorlatinib, a next generation ROS1/ALK inhibitor, remain the activity against D2033 N mutation.	Crizotinib	164-174	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	202-206
29738763-8	2018	This eventually enabled us to engraft and stably grow the cells in vivo, and subsequently evaluate various ROS1 inhibitors against HCC78xe3 cells by overexpressing crizotinib-resistant mutations in the ROS1 kinase domain including G2032R and D2033 N. We newly found that lorlatinib, a next generation ROS1/ALK inhibitor, remain the activity against D2033 N mutation.	Crizotinib	164-174	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	202-206
29738763-9	2018	Furthermore, we demonstrated that HCC78xe3 cells expressing SLC34A2-ROS1 G2032R, and D2033 N, but not wild type (WT) cells, were resistant to crizotinib in vivo.	Crizotinib	142-152	solute carrier family 34 member 2	Homo sapiens	60-67
29738763-9	2018	Furthermore, we demonstrated that HCC78xe3 cells expressing SLC34A2-ROS1 G2032R, and D2033 N, but not wild type (WT) cells, were resistant to crizotinib in vivo.	Crizotinib	142-152	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	68-72
29950868-0	2018	lincROR influences the stemness and crizotinib resistance in EML-ALK+ non-small-cell lung cancer cells.	Crizotinib	36-46	long intergenic non-protein coding RNA, regulator of reprogramming	Homo sapiens	0-7
29950868-0	2018	lincROR influences the stemness and crizotinib resistance in EML-ALK+ non-small-cell lung cancer cells.	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	65-68
29950868-2	2018	Crizotinib is commonly used for EML4-ALK+ NSCLC treatment, but its acquired resistance results in tumor recurrence.	Crizotinib	0-10	EMAP like 4	Homo sapiens	32-36
29950868-2	2018	Crizotinib is commonly used for EML4-ALK+ NSCLC treatment, but its acquired resistance results in tumor recurrence.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	37-40
29950868-12	2018	Conclusion: We found that lincROR expression was significantly inhibited because of the increased concentration of crizotinib in EML4-ALK+ NSCLC cells.	Crizotinib	115-125	long intergenic non-protein coding RNA, regulator of reprogramming	Homo sapiens	26-33
29950868-12	2018	Conclusion: We found that lincROR expression was significantly inhibited because of the increased concentration of crizotinib in EML4-ALK+ NSCLC cells.	Crizotinib	115-125	EMAP like 4	Homo sapiens	129-133
29950868-12	2018	Conclusion: We found that lincROR expression was significantly inhibited because of the increased concentration of crizotinib in EML4-ALK+ NSCLC cells.	Crizotinib	115-125	ALK receptor tyrosine kinase	Homo sapiens	134-137
29950868-13	2018	Furthermore, lincROR overexpression increased cell viability of EML4-ALK+ NSCLC cells, which was impaired by crizotinib.	Crizotinib	109-119	long intergenic non-protein coding RNA, regulator of reprogramming	Homo sapiens	13-20
29950868-13	2018	Furthermore, lincROR overexpression increased cell viability of EML4-ALK+ NSCLC cells, which was impaired by crizotinib.	Crizotinib	109-119	EMAP like 4	Homo sapiens	64-68
29950868-13	2018	Furthermore, lincROR overexpression increased cell viability of EML4-ALK+ NSCLC cells, which was impaired by crizotinib.	Crizotinib	109-119	ALK receptor tyrosine kinase	Homo sapiens	69-72
30258534-4	2018	A retrospective case study of crizotinib and lorlatinib bound to both c-ros oncogene 1 kinase (ROS1) and anaplastic lymphoma kinase (ALK) L1196M related normalized B-factors to differences in binding affinity.	Crizotinib	30-40	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	70-93
30258534-4	2018	A retrospective case study of crizotinib and lorlatinib bound to both c-ros oncogene 1 kinase (ROS1) and anaplastic lymphoma kinase (ALK) L1196M related normalized B-factors to differences in binding affinity.	Crizotinib	30-40	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	95-99
30258534-4	2018	A retrospective case study of crizotinib and lorlatinib bound to both c-ros oncogene 1 kinase (ROS1) and anaplastic lymphoma kinase (ALK) L1196M related normalized B-factors to differences in binding affinity.	Crizotinib	30-40	ALK receptor tyrosine kinase	Homo sapiens	105-131
30258534-4	2018	A retrospective case study of crizotinib and lorlatinib bound to both c-ros oncogene 1 kinase (ROS1) and anaplastic lymphoma kinase (ALK) L1196M related normalized B-factors to differences in binding affinity.	Crizotinib	30-40	ALK receptor tyrosine kinase	Homo sapiens	133-136
29915248-2	2018	We previously showed that the tyrosine kinase inhibitor (TKI) crizotinib inhibits OCT2-mediated transport of creatinine.	Crizotinib	62-72	solute carrier family 22 member 2	Rattus norvegicus	82-86
29915248-3	2018	In the present work, we examined the inhibitory potency of TKIs, including crizotinib, on MATE1-mediated transport of creatinine.	Crizotinib	75-85	solute carrier family 47 member 1	Rattus norvegicus	90-95
29915248-5	2018	Crizotinib inhibited [14C]creatinine uptake by MATE1-overexpressing cells, and the inhibitory effect increased with incubation time, being greater in the case of pre-incubation or combined pre-incubation/co-incubation (pre/co-incubation) than in the case of co-incubation alone.	Crizotinib	0-10	solute carrier family 47 member 1	Rattus norvegicus	47-52
29559559-9	2018	Alectinib was more effective than crizotinib in inhibiting ALK F1174C-expressing cell growth.Conclusions: These findings implicate ALK-activating mutations in SCCP pathogenesis and suggest the therapeutic potential of targeting ALK molecular alterations in some patients with SCCP.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	59-62
29930762-4	2018	We established three types of ALK-TKI (crizotinib, alectinib and ceritinib)-resistant H2228 NSCLC cell lines by high exposure and stepwise methods.	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	30-33
29930762-9	2018	Some ALK-positive NSCLC patients with AXL overexpression showed a poorer response to crizotinib therapy than patients with a low expression of AXL.	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	5-8
29930762-9	2018	Some ALK-positive NSCLC patients with AXL overexpression showed a poorer response to crizotinib therapy than patients with a low expression of AXL.	Crizotinib	85-95	AXL receptor tyrosine kinase	Homo sapiens	38-41
29668860-0	2018	Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	55-81
29668860-0	2018	Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	83-86
29668860-11	2018	Conclusion: Alectinib significantly improved systemic and CNS efficacy versus chemotherapy for crizotinib-pretreated ALK-positive NSCLC patients, with a favorable safety profile.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	117-120
30010763-1	2018	Background: In clinical trials of patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) treated with crizotinib, evaluation of the relationship between the percentage of ALK-positive cells by fluorescence in situ hybridization (FISH)-particularly near the cut-off defining positive status-and clinical outcomes have been limited by small sample sizes.	Crizotinib	138-148	ALK receptor tyrosine kinase	Homo sapiens	48-74
30010763-1	2018	Background: In clinical trials of patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) treated with crizotinib, evaluation of the relationship between the percentage of ALK-positive cells by fluorescence in situ hybridization (FISH)-particularly near the cut-off defining positive status-and clinical outcomes have been limited by small sample sizes.	Crizotinib	138-148	ALK receptor tyrosine kinase	Homo sapiens	76-79
30010763-2	2018	Patients and methods: Data were pooled from three large prospective trials (one single-arm and two randomized versus chemotherapy) of crizotinib in patients with ALK-positive NSCLC determined by Vysis ALK Break Apart FISH using a cut-off of >=15% ALK-positive cells.	Crizotinib	134-144	ALK receptor tyrosine kinase	Homo sapiens	162-165
30010763-2	2018	Patients and methods: Data were pooled from three large prospective trials (one single-arm and two randomized versus chemotherapy) of crizotinib in patients with ALK-positive NSCLC determined by Vysis ALK Break Apart FISH using a cut-off of >=15% ALK-positive cells.	Crizotinib	134-144	ALK receptor tyrosine kinase	Homo sapiens	201-204
30010763-2	2018	Patients and methods: Data were pooled from three large prospective trials (one single-arm and two randomized versus chemotherapy) of crizotinib in patients with ALK-positive NSCLC determined by Vysis ALK Break Apart FISH using a cut-off of >=15% ALK-positive cells.	Crizotinib	134-144	ALK receptor tyrosine kinase	Homo sapiens	201-204
30010763-7	2018	Objective response rate for ALK-positive, crizotinib-treated patients with >=20% ALK-positive cells was 56% (n = 700/1246), 55% (n = 725/1312) for those with >=15% ALK-positive cells, and 38% for those with 15%-19% ALK-positive cells (n = 25/66).	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	81-84
30010763-7	2018	Objective response rate for ALK-positive, crizotinib-treated patients with >=20% ALK-positive cells was 56% (n = 700/1246), 55% (n = 725/1312) for those with >=15% ALK-positive cells, and 38% for those with 15%-19% ALK-positive cells (n = 25/66).	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	81-84
30010763-7	2018	Objective response rate for ALK-positive, crizotinib-treated patients with >=20% ALK-positive cells was 56% (n = 700/1246), 55% (n = 725/1312) for those with >=15% ALK-positive cells, and 38% for those with 15%-19% ALK-positive cells (n = 25/66).	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	81-84
29310482-0	2018	Anaplastic lymphoma kinase (ALK)-rearranged pulmonary pleomorphic carcinoma successfully treated with crizotinib.	Crizotinib	102-112	ALK receptor tyrosine kinase	Homo sapiens	0-26
29310482-0	2018	Anaplastic lymphoma kinase (ALK)-rearranged pulmonary pleomorphic carcinoma successfully treated with crizotinib.	Crizotinib	102-112	ALK receptor tyrosine kinase	Homo sapiens	28-31
29310482-2	2018	Here we present a patient with anaplastic lymphoma kinase (ALK)-rearranged advanced PPC treated with crizotinib.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	31-57
29310482-2	2018	Here we present a patient with anaplastic lymphoma kinase (ALK)-rearranged advanced PPC treated with crizotinib.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	59-62
29862659-2	2018	Herein, we report a case of a lung cancer patient with ALK rearrangement who experienced brain, leptomeningeal, and intradural extramedullary spinal cord metastases after developing resistance to crizotinib.	Crizotinib	196-206	ALK receptor tyrosine kinase	Homo sapiens	55-58
29570100-8	2018	Western blot analysis indicated that both crizotinib and ceritinib inhibited ALK, AKT, and ERK phosphorylations.	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	77-80
29570100-8	2018	Western blot analysis indicated that both crizotinib and ceritinib inhibited ALK, AKT, and ERK phosphorylations.	Crizotinib	42-52	AKT serine/threonine kinase 1	Homo sapiens	82-85
29570100-8	2018	Western blot analysis indicated that both crizotinib and ceritinib inhibited ALK, AKT, and ERK phosphorylations.	Crizotinib	42-52	mitogen-activated protein kinase 1	Homo sapiens	91-94
28701030-0	2018	Crizotinib versus Chemotherapy in Asian Patients with ALK-Positive Advanced Non-small Cell Lung Cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	54-57
28701030-1	2018	Purpose: Crizotinib has demonstrated superior progression-free survival (PFS) and objective response rates (ORRs) versus chemotherapy in previously treated and untreated patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC).	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	184-210
28701030-1	2018	Purpose: Crizotinib has demonstrated superior progression-free survival (PFS) and objective response rates (ORRs) versus chemotherapy in previously treated and untreated patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC).	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	212-215
28701030-10	2018	Conclusion: These data, currently the only analysis showing Asian and non-Asian populations in the same study, support the efficacy and safety of crizotinib in Asian patients with previously treated or untreated ALK-positive advanced NSCLC.	Crizotinib	146-156	ALK receptor tyrosine kinase	Homo sapiens	212-215
29618618-5	2018	Levels of IP3R3 were significantly reduced in both cells and tumors after treatment with crizotinib, whereas EGFR inhibitors caused a reduction of IP3R3 interaction with K-Ras mainly through dephosphorylation of serine residues of K-Ras.Conclusions: Our findings indicate that 18F-FLT PET/CT is able to detect the enhanced efficacy of EGFR and MET inhibitors in oncogene-driven NSCLC and that such enhancement is mediated by IP3R3 through its interaction with K-Ras.	Crizotinib	89-99	inositol 1,4,5-triphosphate receptor 3	Mus musculus	10-15
30024628-11	2018	In vitro experiments demonstrated that S-Crizotinib, the hMTH1 inhibitor, could inhibit proliferation and induce apoptosis and DNA damage of ACC-M cells.	Crizotinib	39-51	nudix hydrolase 1	Homo sapiens	57-62
30024628-13	2018	Meanwhile, S-Crizotinib induced DNA damage in ACC-M cells, indicating that hMTH1 induced the metastasis and recurrence of parotid adenoma by repairing DNA damage, providing a new strategy for the prevention and treatment of parotid adenoma.	Crizotinib	11-23	nudix hydrolase 1	Homo sapiens	75-80
29961337-2	2018	Since crizotinib was approved by the US FDA for the treatment of advanced ROS1-positive non-small-cell lung cancer, ROS1 kinase has become a promising therapeutic target.	Crizotinib	6-16	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	74-78
29961337-2	2018	Since crizotinib was approved by the US FDA for the treatment of advanced ROS1-positive non-small-cell lung cancer, ROS1 kinase has become a promising therapeutic target.	Crizotinib	6-16	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	116-120
29704675-1	2018	INTRODUCTION: ROS1 rearrangement-positive NSCLC can be treated effectively with an anaplastic lymphoma kinase/ROS1/mesenchymal-epithelial transition factor inhibitor such as crizotinib; however, the rate of response remains variable.	Crizotinib	174-184	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	14-18
29704675-1	2018	INTRODUCTION: ROS1 rearrangement-positive NSCLC can be treated effectively with an anaplastic lymphoma kinase/ROS1/mesenchymal-epithelial transition factor inhibitor such as crizotinib; however, the rate of response remains variable.	Crizotinib	174-184	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	110-114
29704675-2	2018	Although several ROS1 fusion partners have been identified, the efficacy of crizotinib in patients with different types of ROS1 fusion partners is poorly understood.	Crizotinib	76-86	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	123-127
29704675-3	2018	METHODS: We reviewed clinicopathological data of patients with ROS1 rearrangement who received crizotinib therapy at our institution between April 2014 and December 2016.	Crizotinib	95-105	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	63-67
29704675-13	2018	Although not independently significant, a trend toward improved survival was observed in patients in the non-CD74-ROS1 group when they were treated with crizotinib.	Crizotinib	153-163	CD74 molecule	Homo sapiens	109-113
29704675-13	2018	Although not independently significant, a trend toward improved survival was observed in patients in the non-CD74-ROS1 group when they were treated with crizotinib.	Crizotinib	153-163	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	114-118
29451020-4	2018	An ALK inhibitor (crizotinib, ceritinib and alectinib) is the preferred therapeutic approach to those advanced ALK fusion variant-positive NSCLC patients.	Crizotinib	18-28	ALK receptor tyrosine kinase	Homo sapiens	111-114
29506392-1	2018	Despite significant advancements in the treatment of anaplastic lymphoma kinase (ALK) positive non-small-cell lung cancer (NSCLC) since the advent of crizotinib, the development of acquired resistance and poor CNS efficacy have necessitated the search for novel and more robust therapies.	Crizotinib	150-160	ALK receptor tyrosine kinase	Homo sapiens	81-84
29910649-11	2018	The treatment algorithm for ALK rearrangement has changed with the proven superiority of alectinib compared with crizotinib in the first-line setting.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	28-31
29910649-12	2018	The approval of crizotinib for ROS1 rearrangements now means that patients also must be tested for that mutation.	Crizotinib	16-26	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	31-35
30258534-0	2018	Reviving B-Factors: Retrospective Normalized B-Factor Analysis of c-ros Oncogene 1 Receptor Tyrosine Kinase and Anaplastic Lymphoma Kinase L1196M with Crizotinib and Lorlatinib.	Crizotinib	151-161	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	66-107
29669701-2	2018	We assessed the activity and safety of crizotinib, a tyrosine kinase inhibitor, targeting ALK in patients with advanced IMFT either with or without ALK alterations.	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	90-93
29058790-5	2018	One of these is crizotinib (a dual c-Met/ALK inhibitor).	Crizotinib	16-26	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	35-40
29058790-5	2018	One of these is crizotinib (a dual c-Met/ALK inhibitor).	Crizotinib	16-26	ALK receptor tyrosine kinase	Homo sapiens	41-44
29669701-19	2018	Crizotinib could be considered as the standard of care for patients with locally advanced or metastatic ALK-positive IMFT who do not qualify for curative surgery.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	104-107
29855474-0	2018	(S)-crizotinib reduces gastric cancer growth through oxidative DNA damage and triggers pro-survival akt signal.	Crizotinib	0-14	thymoma viral proto-oncogene 1	Mus musculus	100-103
29805608-1	2018	Crizotinib is an anti-cancer drug with a substantial beneficial effect in advanced non-small-cell lung cancer (NSCLC) patients harboring anaplastic lymphoma kinase (ALK) rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	137-163
29805608-1	2018	Crizotinib is an anti-cancer drug with a substantial beneficial effect in advanced non-small-cell lung cancer (NSCLC) patients harboring anaplastic lymphoma kinase (ALK) rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	165-168
29805608-12	2018	In conclusion, the present real-world study revealed that the use of crizotinib improved the long-term survival of patients with ALK-positive advanced NSCLC.	Crizotinib	69-79	ALK receptor tyrosine kinase	Homo sapiens	129-132
29512859-3	2018	We report on five patients with progressive or early relapsed ALK-positive ALCL who developed CNS progression during re-induction with vinblastine, crizotinib, or brentuximab vedotin given for bridging to allogeneic blood stem cell transplantation.	Crizotinib	148-158	ALK receptor tyrosine kinase	Homo sapiens	62-65
29807641-4	2018	Targeted therapies are aimed at the products of these gene mutations and include erlotinib (used in epidermal growth factor receptor mutant NSCLC) and crizotinib (used in anaplastic lymphoma kinase positive NSCLC).	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	171-197
29855474-8	2018	Results indicated that (S)-crizotinib decreased GC cell viability, induced growth arrest and apoptosis, and increased levels of gammaH2AX and Ser1981-phosphorylated ATM, which were inhibited by NAC.	Crizotinib	23-37	H2A.X variant histone	Mus musculus	128-137
29855474-8	2018	Results indicated that (S)-crizotinib decreased GC cell viability, induced growth arrest and apoptosis, and increased levels of gammaH2AX and Ser1981-phosphorylated ATM, which were inhibited by NAC.	Crizotinib	23-37	ataxia telangiectasia mutated	Mus musculus	165-168
29855474-8	2018	Results indicated that (S)-crizotinib decreased GC cell viability, induced growth arrest and apoptosis, and increased levels of gammaH2AX and Ser1981-phosphorylated ATM, which were inhibited by NAC.	Crizotinib	23-37	NLR family, pyrin domain containing 1A	Mus musculus	194-197
29855474-10	2018	Moreover, ATM-activated Akt, a pro-survival signal, whose inhibition further enhanced (S)-crizotinib-induced inhibition of GC cell growth and tumor growth in xenograft mice, and re-sensitized resistant GC cells to (S)-crizotinib.	Crizotinib	86-100	ataxia telangiectasia mutated	Mus musculus	10-13
29855474-10	2018	Moreover, ATM-activated Akt, a pro-survival signal, whose inhibition further enhanced (S)-crizotinib-induced inhibition of GC cell growth and tumor growth in xenograft mice, and re-sensitized resistant GC cells to (S)-crizotinib.	Crizotinib	86-100	thymoma viral proto-oncogene 1	Mus musculus	24-27
29855474-10	2018	Moreover, ATM-activated Akt, a pro-survival signal, whose inhibition further enhanced (S)-crizotinib-induced inhibition of GC cell growth and tumor growth in xenograft mice, and re-sensitized resistant GC cells to (S)-crizotinib.	Crizotinib	214-228	ataxia telangiectasia mutated	Mus musculus	10-13
29855474-10	2018	Moreover, ATM-activated Akt, a pro-survival signal, whose inhibition further enhanced (S)-crizotinib-induced inhibition of GC cell growth and tumor growth in xenograft mice, and re-sensitized resistant GC cells to (S)-crizotinib.	Crizotinib	214-228	thymoma viral proto-oncogene 1	Mus musculus	24-27
29855474-11	2018	(S)-crizotinib reduced GC cell and tumor growth through oxidative DNA damage mechanism and triggered pro-survival Akt signaling.	Crizotinib	4-14	thymoma viral proto-oncogene 1	Mus musculus	114-117
29855474-12	2018	We conclude that inclusion of Akt inhibition (to block the survival signaling) with (S)-crizotinib may provide an effective and novel combination therapy for GC in the clinical setting.	Crizotinib	84-98	thymoma viral proto-oncogene 1	Mus musculus	30-33
29844259-0	2018	Real-World Use and Outcomes of ALK-Positive Crizotinib-Treated Metastatic NSCLC in US Community Oncology Practices: A Retrospective Observational Study.	Crizotinib	44-54	ALK receptor tyrosine kinase	Homo sapiens	31-34
29844259-2	2018	Crizotinib was the first approved ALK inhibitor from clinical trials.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	34-37
29844259-4	2018	METHODS: This was a retrospective, observational study of adult crizotinib-treated ALK-positive metastatic NSCLC patients who received treatment between 1 September 2011 and 31 October 2014, with follow up through 31 December 2015.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	83-86
29844259-7	2018	RESULTS: Of the n = 199 ALK-positive crizotinib-treated patients meeting eligibility criteria, crizotinib was prescribed as first line (1 L) in n = 123 (61.8%).	Crizotinib	37-47	ALK receptor tyrosine kinase	Homo sapiens	24-27
29596029-2	2018	Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and MET, has shown marked antitumor activity in a small expansion cohort of patients with ROS1-positive advanced NSCLC from an ongoing phase I study.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	28-54
29596029-2	2018	Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and MET, has shown marked antitumor activity in a small expansion cohort of patients with ROS1-positive advanced NSCLC from an ongoing phase I study.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	56-59
29596029-2	2018	Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and MET, has shown marked antitumor activity in a small expansion cohort of patients with ROS1-positive advanced NSCLC from an ongoing phase I study.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	62-66
29596029-2	2018	Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and MET, has shown marked antitumor activity in a small expansion cohort of patients with ROS1-positive advanced NSCLC from an ongoing phase I study.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	158-162
29596029-3	2018	We assessed the efficacy and safety of crizotinib in the largest cohort of patients with ROS1-positive advanced NSCLC.	Crizotinib	39-49	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	89-93
29596029-12	2018	Conclusion This study demonstrated clinically meaningful benefit and durable responses with crizotinib in East Asian patients with ROS1-positive advanced NSCLC.	Crizotinib	92-102	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	131-135
29455091-1	2018	CT-707, a mutant-selective inhibitor of an important cancer target, anaplastic lymphoma kinase (ALK), is designed to be a targeted therapeutic agent for non-small cell lung cancer (NSCLC) patients harboring ALK active and crizotinib resistant mutations.	Crizotinib	222-232	ALK receptor tyrosine kinase	Homo sapiens	68-94
29455091-1	2018	CT-707, a mutant-selective inhibitor of an important cancer target, anaplastic lymphoma kinase (ALK), is designed to be a targeted therapeutic agent for non-small cell lung cancer (NSCLC) patients harboring ALK active and crizotinib resistant mutations.	Crizotinib	222-232	ALK receptor tyrosine kinase	Homo sapiens	96-99
29764505-2	2018	We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK- and EGFR-targeted TKIs crizotinib and osimertinib, respectively.	Crizotinib	215-225	ALK receptor tyrosine kinase	Homo sapiens	187-190
29764505-2	2018	We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK- and EGFR-targeted TKIs crizotinib and osimertinib, respectively.	Crizotinib	215-225	epidermal growth factor receptor	Homo sapiens	196-200
29743557-4	2018	We found that combined treatment with ABT263 and Crizotinib synergistically reduces the proliferation of glioblastoma cells, which was dependent on dual inhibition of Bcl-2 and Bcl-xL.	Crizotinib	49-59	BCL2 apoptosis regulator	Homo sapiens	167-172
29743557-4	2018	We found that combined treatment with ABT263 and Crizotinib synergistically reduces the proliferation of glioblastoma cells, which was dependent on dual inhibition of Bcl-2 and Bcl-xL.	Crizotinib	49-59	BCL2 like 1	Homo sapiens	177-183
29595984-7	2018	ALK-specific inhibitors, including Crizotinib, Ceritinib, and TAE684, exhibited less effects on H3122 cells preincubated with Exo-Apo than on those treated with Exo-Ctrl in either inhibition of cell viability or promotion of apoptosis.	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	0-3
29610932-0	2018	EML4-ALK rearrangement in squamous cell carcinoma shows significant response to anti-ALK inhibitor drugs crizotinib and alectinib.	Crizotinib	105-115	EMAP like 4	Homo sapiens	0-4
29610932-0	2018	EML4-ALK rearrangement in squamous cell carcinoma shows significant response to anti-ALK inhibitor drugs crizotinib and alectinib.	Crizotinib	105-115	ALK receptor tyrosine kinase	Homo sapiens	5-8
29610932-0	2018	EML4-ALK rearrangement in squamous cell carcinoma shows significant response to anti-ALK inhibitor drugs crizotinib and alectinib.	Crizotinib	105-115	ALK receptor tyrosine kinase	Homo sapiens	85-88
29951342-0	2018	Primary resistance to crizotinib treatment in a non-small cell lung cancer patient with an EML4-ALK rearrangement: a case report.	Crizotinib	22-32	EMAP like 4	Homo sapiens	91-95
29951342-0	2018	Primary resistance to crizotinib treatment in a non-small cell lung cancer patient with an EML4-ALK rearrangement: a case report.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	96-99
29951342-1	2018	Crizotinib, a small molecular tyrosine kinase inhibitor, manifests dramatic responses in patients with non-small cell lung cancer with echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangements.	Crizotinib	0-10	EMAP like 4	Homo sapiens	212-216
29951342-1	2018	Crizotinib, a small molecular tyrosine kinase inhibitor, manifests dramatic responses in patients with non-small cell lung cancer with echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangements.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	217-220
29951342-2	2018	ALK gene point mutation is the primary mechanism of acquired crizotinib resistance; however, the intrinsic mechanism is not fully understood.	Crizotinib	61-71	ALK receptor tyrosine kinase	Homo sapiens	0-3
29951342-3	2018	Here, we report a patient with a low mutant allele fraction (MAF) of EML4-ALK rearrangement, who experienced primary resistance to crizotinib treatment.	Crizotinib	131-141	EMAP like 4	Homo sapiens	69-73
29951342-3	2018	Here, we report a patient with a low mutant allele fraction (MAF) of EML4-ALK rearrangement, who experienced primary resistance to crizotinib treatment.	Crizotinib	131-141	ALK receptor tyrosine kinase	Homo sapiens	74-77
29951342-11	2018	The MAF of EML4-ALK rearrangements in cancer cells might be a predictive factor for crizotinib treatment.	Crizotinib	84-94	EMAP like 4	Homo sapiens	11-15
29951342-11	2018	The MAF of EML4-ALK rearrangements in cancer cells might be a predictive factor for crizotinib treatment.	Crizotinib	84-94	ALK receptor tyrosine kinase	Homo sapiens	16-19
29997961-1	2018	Background: Non-small cell lung cancer (NSCLC) patients with EML4-ALK fusion exhibited various durations of response to crizotinib.	Crizotinib	120-130	EMAP like 4	Homo sapiens	61-65
29997961-1	2018	Background: Non-small cell lung cancer (NSCLC) patients with EML4-ALK fusion exhibited various durations of response to crizotinib.	Crizotinib	120-130	ALK receptor tyrosine kinase	Homo sapiens	66-69
29997966-0	2018	TP53 mutations predict for poor survival in ALK rearrangement lung adenocarcinoma patients treated with crizotinib.	Crizotinib	104-114	tumor protein p53	Homo sapiens	0-4
29997966-0	2018	TP53 mutations predict for poor survival in ALK rearrangement lung adenocarcinoma patients treated with crizotinib.	Crizotinib	104-114	ALK receptor tyrosine kinase	Homo sapiens	44-47
29997966-1	2018	Background: Advanced non-small cell lung cancer (NSCLC) patients who harbor anaplastic lymphoma kinase (ALK) rearrangement are sensitive to an ALK inhibitor (crizotinib), but not all ALK-positive patients benefit equally from crizotinib treatment.	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	76-102
29997966-1	2018	Background: Advanced non-small cell lung cancer (NSCLC) patients who harbor anaplastic lymphoma kinase (ALK) rearrangement are sensitive to an ALK inhibitor (crizotinib), but not all ALK-positive patients benefit equally from crizotinib treatment.	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	104-107
29997966-1	2018	Background: Advanced non-small cell lung cancer (NSCLC) patients who harbor anaplastic lymphoma kinase (ALK) rearrangement are sensitive to an ALK inhibitor (crizotinib), but not all ALK-positive patients benefit equally from crizotinib treatment.	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	143-146
29997966-1	2018	Background: Advanced non-small cell lung cancer (NSCLC) patients who harbor anaplastic lymphoma kinase (ALK) rearrangement are sensitive to an ALK inhibitor (crizotinib), but not all ALK-positive patients benefit equally from crizotinib treatment.	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	143-146
29997966-2	2018	We analyze the impact of TP53 mutations on response to crizotinib in patients with ALK rearrangement NSCLC.	Crizotinib	55-65	tumor protein p53	Homo sapiens	25-29
29997966-2	2018	We analyze the impact of TP53 mutations on response to crizotinib in patients with ALK rearrangement NSCLC.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	83-86
29997966-10	2018	Conclusions: TP53 mutations reduce responsiveness to crizotinib and worsen prognosis in ALK rearrangement NSCLC patients.	Crizotinib	53-63	tumor protein p53	Homo sapiens	13-17
29327716-2	2018	Evidence of ALK rearrangement occurs in a minority (2-7%) of lung adenocarcinoma, and only ~60% of these patients will respond to targeted ALK inhibition by drugs such as crizotinib and ceritinib.	Crizotinib	171-181	ALK receptor tyrosine kinase	Homo sapiens	12-15
29327716-2	2018	Evidence of ALK rearrangement occurs in a minority (2-7%) of lung adenocarcinoma, and only ~60% of these patients will respond to targeted ALK inhibition by drugs such as crizotinib and ceritinib.	Crizotinib	171-181	ALK receptor tyrosine kinase	Homo sapiens	139-142
29477381-0	2018	CD74-ROS1 G2032R mutation transcriptionally up-regulates Twist1 in non-small cell lung cancer cells leading to increased migration, invasion, and resistance to crizotinib.	Crizotinib	160-170	CD74 molecule	Homo sapiens	0-4
29477381-0	2018	CD74-ROS1 G2032R mutation transcriptionally up-regulates Twist1 in non-small cell lung cancer cells leading to increased migration, invasion, and resistance to crizotinib.	Crizotinib	160-170	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	5-9
29477381-0	2018	CD74-ROS1 G2032R mutation transcriptionally up-regulates Twist1 in non-small cell lung cancer cells leading to increased migration, invasion, and resistance to crizotinib.	Crizotinib	160-170	twist family bHLH transcription factor 1	Homo sapiens	57-63
29477381-2	2018	Although crizotinib has a prominent effect on ROS1, resistance is inevitable.	Crizotinib	9-19	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	46-50
29477381-4	2018	To explore the mechanism of drug resistance, we constructed the crizotinib resistance cell line, A549-CD74-ROS1 G2032R mutation cells, by the methods of fusion polymerase chain reaction (PCR), plasmid construction and cell transfection in vitro.	Crizotinib	64-74	CD74 molecule	Homo sapiens	102-106
29477381-4	2018	To explore the mechanism of drug resistance, we constructed the crizotinib resistance cell line, A549-CD74-ROS1 G2032R mutation cells, by the methods of fusion polymerase chain reaction (PCR), plasmid construction and cell transfection in vitro.	Crizotinib	64-74	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	107-111
29477381-7	2018	Combination of Twist1 siRNA and crizotinib significantly reduced cell vitality, inhibited cell invasion and migration, and promoted apoptosis in A549-CD74-ROS1 G2032R mutation cells.	Crizotinib	32-42	CD74 molecule	Homo sapiens	150-154
29477381-7	2018	Combination of Twist1 siRNA and crizotinib significantly reduced cell vitality, inhibited cell invasion and migration, and promoted apoptosis in A549-CD74-ROS1 G2032R mutation cells.	Crizotinib	32-42	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	155-159
29477381-9	2018	Combination of Twist1 silence and ROS1 inhibitor may provide a potent strategy to treat the ROS1+ NSCLC patients with crizotinib resistance.	Crizotinib	118-128	twist family bHLH transcription factor 1	Homo sapiens	15-21
29477381-9	2018	Combination of Twist1 silence and ROS1 inhibitor may provide a potent strategy to treat the ROS1+ NSCLC patients with crizotinib resistance.	Crizotinib	118-128	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	34-38
29477381-9	2018	Combination of Twist1 silence and ROS1 inhibitor may provide a potent strategy to treat the ROS1+ NSCLC patients with crizotinib resistance.	Crizotinib	118-128	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	92-96
29352732-0	2018	Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): A phase 1b open-label study.	Crizotinib	21-31	ALK receptor tyrosine kinase	Homo sapiens	35-38
29352732-1	2018	Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK-positive or ROS1-positive advanced non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	28-54
29352732-1	2018	Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK-positive or ROS1-positive advanced non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	56-59
29352732-1	2018	Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK-positive or ROS1-positive advanced non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	71-75
29352732-1	2018	Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK-positive or ROS1-positive advanced non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	120-123
29352732-1	2018	Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK-positive or ROS1-positive advanced non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	136-140
29352732-9	2018	These findings indicate strong and durable activity of crizotinib in ALK-positive lymphomas and IMTs.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	69-72
29725387-3	2018	The aim of the present study was to investigate the effects of a c-Met inhibitor, PF-2341066 and a cyclooxygenase-2 (COX-2) inhibitor, celecoxib, on c-Met and COX-2 expression, proliferation and apoptosis.	Crizotinib	82-92	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	149-154
29725387-3	2018	The aim of the present study was to investigate the effects of a c-Met inhibitor, PF-2341066 and a cyclooxygenase-2 (COX-2) inhibitor, celecoxib, on c-Met and COX-2 expression, proliferation and apoptosis.	Crizotinib	82-92	prostaglandin-endoperoxide synthase 2	Homo sapiens	159-164
29518553-1	2018	INTRODUCTION: Crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is a first-line treatment for ALK translocation-positive advanced non-small cell lung cancer (NSCLC); however, patients eventually progress.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	29-55
29518553-1	2018	INTRODUCTION: Crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is a first-line treatment for ALK translocation-positive advanced non-small cell lung cancer (NSCLC); however, patients eventually progress.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	57-60
29518553-1	2018	INTRODUCTION: Crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is a first-line treatment for ALK translocation-positive advanced non-small cell lung cancer (NSCLC); however, patients eventually progress.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	103-106
29518553-4	2018	Herein we report data from a study assessing nivolumab plus crizotinib in patients with previously untreated advanced ALK translocation-positive NSCLC.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	118-121
29656744-1	2018	OBJECTIVES: Despite improved progression-free survival, most patients treated with the first generation ALK inhibitor crizotinib ultimately experience central nervous system (CNS) progression.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	104-107
29656760-0	2018	Successful treatment with brigatinib in a patient with ALK-rearranged lung adenocarcinoma who developed crizotinib-induced interstitial lung disease.	Crizotinib	104-114	ALK receptor tyrosine kinase	Homo sapiens	55-58
29656760-1	2018	We present a 45-year-old patient diagnosed with anaplastic lymphoma kinase (ALK)-rearranged metastatic lung cancer who developed grade 4 interstitial lung disease (ILD) while on crizotinib treatment and was lately treated with brigatinib with no reappearance of ILD.	Crizotinib	178-188	ALK receptor tyrosine kinase	Homo sapiens	48-74
29656760-1	2018	We present a 45-year-old patient diagnosed with anaplastic lymphoma kinase (ALK)-rearranged metastatic lung cancer who developed grade 4 interstitial lung disease (ILD) while on crizotinib treatment and was lately treated with brigatinib with no reappearance of ILD.	Crizotinib	178-188	ALK receptor tyrosine kinase	Homo sapiens	76-79
29796191-4	2018	The L1196M mutation within the ALK fusion gene was detected after failure of consecutive treatment with crizotinib and alectinib, but no other mechanism underlying acquired resistance to ALK-TKIs was found to be operative.	Crizotinib	104-114	ALK receptor tyrosine kinase	Homo sapiens	31-34
29805713-0	2018	Feasibility of continuing crizotinib therapy after RECIST-PD in advanced non-small cell lung cancer patients with ALK/ROS-1 mutations.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	114-117
29517860-3	2018	The multi-targeted MET/ALK/ROS1 tyrosine kinase inhibitor (TKI) crizotinib has demonstrated remarkable efficacy in ROS1-rearranged NSCLC.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	23-26
29517860-3	2018	The multi-targeted MET/ALK/ROS1 tyrosine kinase inhibitor (TKI) crizotinib has demonstrated remarkable efficacy in ROS1-rearranged NSCLC.	Crizotinib	64-74	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	27-31
29517860-3	2018	The multi-targeted MET/ALK/ROS1 tyrosine kinase inhibitor (TKI) crizotinib has demonstrated remarkable efficacy in ROS1-rearranged NSCLC.	Crizotinib	64-74	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	115-119
29805713-0	2018	Feasibility of continuing crizotinib therapy after RECIST-PD in advanced non-small cell lung cancer patients with ALK/ROS-1 mutations.	Crizotinib	26-36	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	118-123
29805713-1	2018	Objectives: To study whether ongoing clinical benefits of continuing anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) inhibition are achieved by crizotinib treatment post progressive disease (PD) in advanced non-small cell lung cancer (NSCLC) patients harboring ALK/ROS1 mutations.	Crizotinib	157-167	ALK receptor tyrosine kinase	Homo sapiens	69-95
29805713-1	2018	Objectives: To study whether ongoing clinical benefits of continuing anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) inhibition are achieved by crizotinib treatment post progressive disease (PD) in advanced non-small cell lung cancer (NSCLC) patients harboring ALK/ROS1 mutations.	Crizotinib	157-167	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	124-128
29805713-10	2018	Conclusion: Continuation of crizotinib therapy after RECIST-PD in Chinese NSCLC patients with positive ALK/ROS1 mutations is feasible in clinical practice.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	103-106
29805713-10	2018	Conclusion: Continuation of crizotinib therapy after RECIST-PD in Chinese NSCLC patients with positive ALK/ROS1 mutations is feasible in clinical practice.	Crizotinib	28-38	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	107-111
29666949-2	2018	Despite the initial response, virtually all ALK-positive patients develop an acquired resistance to the ALK inhibitor crizotinib, usually within 12 months.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	44-47
29666949-2	2018	Despite the initial response, virtually all ALK-positive patients develop an acquired resistance to the ALK inhibitor crizotinib, usually within 12 months.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	104-107
29666949-3	2018	Several next-generation ALK inhibitors have been developed in order to overcome crizotinib limitation, providing an unprecedented survival for this subset of patients.	Crizotinib	80-90	ALK receptor tyrosine kinase	Homo sapiens	24-27
29755689-0	2018	A subgroup of pleural mesothelioma expresses ALK protein and may be targetable by combined rapamycin and crizotinib therapy.	Crizotinib	105-115	ALK receptor tyrosine kinase	Homo sapiens	45-48
29467147-2	2018	SUMMARY: In patients with NSCLC driven by mutations of ALK, the gene coding for anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has been found to provide median progression-free survival (PFS) of 10.9 months; however, therapeutic failures and tumor progression to brain metastases are common with crizotinib use, prompting research to find more potent and tolerable ALK inhibitors that target major oncogenic drivers of NSCLC.	Crizotinib	147-157	ALK receptor tyrosine kinase	Homo sapiens	55-58
29467147-2	2018	SUMMARY: In patients with NSCLC driven by mutations of ALK, the gene coding for anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has been found to provide median progression-free survival (PFS) of 10.9 months; however, therapeutic failures and tumor progression to brain metastases are common with crizotinib use, prompting research to find more potent and tolerable ALK inhibitors that target major oncogenic drivers of NSCLC.	Crizotinib	147-157	ALK receptor tyrosine kinase	Homo sapiens	80-106
29467147-2	2018	SUMMARY: In patients with NSCLC driven by mutations of ALK, the gene coding for anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has been found to provide median progression-free survival (PFS) of 10.9 months; however, therapeutic failures and tumor progression to brain metastases are common with crizotinib use, prompting research to find more potent and tolerable ALK inhibitors that target major oncogenic drivers of NSCLC.	Crizotinib	147-157	ALK receptor tyrosine kinase	Homo sapiens	108-111
29467147-2	2018	SUMMARY: In patients with NSCLC driven by mutations of ALK, the gene coding for anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has been found to provide median progression-free survival (PFS) of 10.9 months; however, therapeutic failures and tumor progression to brain metastases are common with crizotinib use, prompting research to find more potent and tolerable ALK inhibitors that target major oncogenic drivers of NSCLC.	Crizotinib	147-157	ALK receptor tyrosine kinase	Homo sapiens	108-111
29467147-2	2018	SUMMARY: In patients with NSCLC driven by mutations of ALK, the gene coding for anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has been found to provide median progression-free survival (PFS) of 10.9 months; however, therapeutic failures and tumor progression to brain metastases are common with crizotinib use, prompting research to find more potent and tolerable ALK inhibitors that target major oncogenic drivers of NSCLC.	Crizotinib	147-157	ALK receptor tyrosine kinase	Homo sapiens	108-111
29467147-2	2018	SUMMARY: In patients with NSCLC driven by mutations of ALK, the gene coding for anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has been found to provide median progression-free survival (PFS) of 10.9 months; however, therapeutic failures and tumor progression to brain metastases are common with crizotinib use, prompting research to find more potent and tolerable ALK inhibitors that target major oncogenic drivers of NSCLC.	Crizotinib	327-337	ALK receptor tyrosine kinase	Homo sapiens	55-58
29467147-2	2018	SUMMARY: In patients with NSCLC driven by mutations of ALK, the gene coding for anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has been found to provide median progression-free survival (PFS) of 10.9 months; however, therapeutic failures and tumor progression to brain metastases are common with crizotinib use, prompting research to find more potent and tolerable ALK inhibitors that target major oncogenic drivers of NSCLC.	Crizotinib	327-337	ALK receptor tyrosine kinase	Homo sapiens	80-106
29467147-2	2018	SUMMARY: In patients with NSCLC driven by mutations of ALK, the gene coding for anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has been found to provide median progression-free survival (PFS) of 10.9 months; however, therapeutic failures and tumor progression to brain metastases are common with crizotinib use, prompting research to find more potent and tolerable ALK inhibitors that target major oncogenic drivers of NSCLC.	Crizotinib	327-337	ALK receptor tyrosine kinase	Homo sapiens	108-111
29467147-2	2018	SUMMARY: In patients with NSCLC driven by mutations of ALK, the gene coding for anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has been found to provide median progression-free survival (PFS) of 10.9 months; however, therapeutic failures and tumor progression to brain metastases are common with crizotinib use, prompting research to find more potent and tolerable ALK inhibitors that target major oncogenic drivers of NSCLC.	Crizotinib	327-337	ALK receptor tyrosine kinase	Homo sapiens	108-111
29467147-2	2018	SUMMARY: In patients with NSCLC driven by mutations of ALK, the gene coding for anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has been found to provide median progression-free survival (PFS) of 10.9 months; however, therapeutic failures and tumor progression to brain metastases are common with crizotinib use, prompting research to find more potent and tolerable ALK inhibitors that target major oncogenic drivers of NSCLC.	Crizotinib	327-337	ALK receptor tyrosine kinase	Homo sapiens	108-111
29755689-8	2018	The ALK/MET inhibitor crizotinib enhanced the anti-tumor effect of the mTOR-inhibitor rapamycin in a patient-derived MPM xenograft with co-activated ALK/mTOR: combined therapy achieved tumor shrinkage in 4/5 tumors and growth stagnation in one tumor.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	4-7
29755689-8	2018	The ALK/MET inhibitor crizotinib enhanced the anti-tumor effect of the mTOR-inhibitor rapamycin in a patient-derived MPM xenograft with co-activated ALK/mTOR: combined therapy achieved tumor shrinkage in 4/5 tumors and growth stagnation in one tumor.	Crizotinib	22-32	mechanistic target of rapamycin kinase	Homo sapiens	71-75
29755689-8	2018	The ALK/MET inhibitor crizotinib enhanced the anti-tumor effect of the mTOR-inhibitor rapamycin in a patient-derived MPM xenograft with co-activated ALK/mTOR: combined therapy achieved tumor shrinkage in 4/5 tumors and growth stagnation in one tumor.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	149-152
29755689-8	2018	The ALK/MET inhibitor crizotinib enhanced the anti-tumor effect of the mTOR-inhibitor rapamycin in a patient-derived MPM xenograft with co-activated ALK/mTOR: combined therapy achieved tumor shrinkage in 4/5 tumors and growth stagnation in one tumor.	Crizotinib	22-32	mechanistic target of rapamycin kinase	Homo sapiens	153-157
29755689-11	2018	Rapamycin/crizotinib simultaneously inhibited mTORC1 (evidenced by S6 kinase and RPS6 dephosphorylation) and ALK signaling (ALK, AKT, STAT3 dephosphorylation), and crizotinib suppressed the adverse AKT activation induced by rapamycin.	Crizotinib	10-20	CREB regulated transcription coactivator 1	Mus musculus	46-52
29755689-11	2018	Rapamycin/crizotinib simultaneously inhibited mTORC1 (evidenced by S6 kinase and RPS6 dephosphorylation) and ALK signaling (ALK, AKT, STAT3 dephosphorylation), and crizotinib suppressed the adverse AKT activation induced by rapamycin.	Crizotinib	10-20	ribosomal protein S6	Homo sapiens	81-85
29755689-11	2018	Rapamycin/crizotinib simultaneously inhibited mTORC1 (evidenced by S6 kinase and RPS6 dephosphorylation) and ALK signaling (ALK, AKT, STAT3 dephosphorylation), and crizotinib suppressed the adverse AKT activation induced by rapamycin.	Crizotinib	10-20	ALK receptor tyrosine kinase	Homo sapiens	109-112
29755689-11	2018	Rapamycin/crizotinib simultaneously inhibited mTORC1 (evidenced by S6 kinase and RPS6 dephosphorylation) and ALK signaling (ALK, AKT, STAT3 dephosphorylation), and crizotinib suppressed the adverse AKT activation induced by rapamycin.	Crizotinib	10-20	ALK receptor tyrosine kinase	Homo sapiens	124-127
29755689-11	2018	Rapamycin/crizotinib simultaneously inhibited mTORC1 (evidenced by S6 kinase and RPS6 dephosphorylation) and ALK signaling (ALK, AKT, STAT3 dephosphorylation), and crizotinib suppressed the adverse AKT activation induced by rapamycin.	Crizotinib	10-20	AKT serine/threonine kinase 1	Homo sapiens	129-132
29755689-11	2018	Rapamycin/crizotinib simultaneously inhibited mTORC1 (evidenced by S6 kinase and RPS6 dephosphorylation) and ALK signaling (ALK, AKT, STAT3 dephosphorylation), and crizotinib suppressed the adverse AKT activation induced by rapamycin.	Crizotinib	10-20	signal transducer and activator of transcription 3	Homo sapiens	134-139
29755689-11	2018	Rapamycin/crizotinib simultaneously inhibited mTORC1 (evidenced by S6 kinase and RPS6 dephosphorylation) and ALK signaling (ALK, AKT, STAT3 dephosphorylation), and crizotinib suppressed the adverse AKT activation induced by rapamycin.	Crizotinib	10-20	AKT serine/threonine kinase 1	Homo sapiens	198-201
29444468-0	2018	A major component of vitamin E, alpha-tocopherol inhibits the anti-tumor activity of crizotinib against cells transformed by EML4-ALK.	Crizotinib	85-95	EMAP like 4	Homo sapiens	125-129
29444468-0	2018	A major component of vitamin E, alpha-tocopherol inhibits the anti-tumor activity of crizotinib against cells transformed by EML4-ALK.	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	130-133
29444468-1	2018	Crizotinib is an inhibitor of anaplastic lymphoma kinase (ALK) and is of significant therapeutic benefit to patients with non-small cell lung cancer (NSCLC) harboring the EML4-ALK fusion gene.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	30-56
29444468-1	2018	Crizotinib is an inhibitor of anaplastic lymphoma kinase (ALK) and is of significant therapeutic benefit to patients with non-small cell lung cancer (NSCLC) harboring the EML4-ALK fusion gene.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	58-61
29444468-1	2018	Crizotinib is an inhibitor of anaplastic lymphoma kinase (ALK) and is of significant therapeutic benefit to patients with non-small cell lung cancer (NSCLC) harboring the EML4-ALK fusion gene.	Crizotinib	0-10	EMAP like 4	Homo sapiens	171-175
29444468-1	2018	Crizotinib is an inhibitor of anaplastic lymphoma kinase (ALK) and is of significant therapeutic benefit to patients with non-small cell lung cancer (NSCLC) harboring the EML4-ALK fusion gene.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	176-179
29444468-3	2018	alpha-Tocopherol significantly inhibited crizotinib-induced apoptosis in cells transformed by EML4-ALK.	Crizotinib	41-51	EMAP like 4	Homo sapiens	94-98
29444468-3	2018	alpha-Tocopherol significantly inhibited crizotinib-induced apoptosis in cells transformed by EML4-ALK.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	99-102
29444468-4	2018	It also effectively attenuated the crizotinib-induced inhibition of EML4-ALK and its downstream molecules, STAT3 and ERK, and suppressed the inhibitory effects of crizotinib on EML4-ALK-mediated transformation in the focus formation assay.	Crizotinib	35-45	EMAP like 4	Homo sapiens	68-72
29444468-4	2018	It also effectively attenuated the crizotinib-induced inhibition of EML4-ALK and its downstream molecules, STAT3 and ERK, and suppressed the inhibitory effects of crizotinib on EML4-ALK-mediated transformation in the focus formation assay.	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	73-76
29444468-4	2018	It also effectively attenuated the crizotinib-induced inhibition of EML4-ALK and its downstream molecules, STAT3 and ERK, and suppressed the inhibitory effects of crizotinib on EML4-ALK-mediated transformation in the focus formation assay.	Crizotinib	35-45	signal transducer and activator of transcription 3	Homo sapiens	107-112
29444468-4	2018	It also effectively attenuated the crizotinib-induced inhibition of EML4-ALK and its downstream molecules, STAT3 and ERK, and suppressed the inhibitory effects of crizotinib on EML4-ALK-mediated transformation in the focus formation assay.	Crizotinib	35-45	mitogen-activated protein kinase 1	Homo sapiens	117-120
29444468-4	2018	It also effectively attenuated the crizotinib-induced inhibition of EML4-ALK and its downstream molecules, STAT3 and ERK, and suppressed the inhibitory effects of crizotinib on EML4-ALK-mediated transformation in the focus formation assay.	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	182-185
29444468-4	2018	It also effectively attenuated the crizotinib-induced inhibition of EML4-ALK and its downstream molecules, STAT3 and ERK, and suppressed the inhibitory effects of crizotinib on EML4-ALK-mediated transformation in the focus formation assay.	Crizotinib	163-173	EMAP like 4	Homo sapiens	177-181
29444468-4	2018	It also effectively attenuated the crizotinib-induced inhibition of EML4-ALK and its downstream molecules, STAT3 and ERK, and suppressed the inhibitory effects of crizotinib on EML4-ALK-mediated transformation in the focus formation assay.	Crizotinib	163-173	ALK receptor tyrosine kinase	Homo sapiens	182-185
29642919-1	2018	BACKGROUND: ALK rearrangement-advanced NSCLC patients respond to crizotinib.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	12-15
29437595-6	2018	Crizotinib, an ALK/ROS1 inhibitor, markedly suppressed ALK/ROS1 fusion-positive JMML cell proliferation in vitro.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	15-18
29437595-6	2018	Crizotinib, an ALK/ROS1 inhibitor, markedly suppressed ALK/ROS1 fusion-positive JMML cell proliferation in vitro.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	19-23
29437595-6	2018	Crizotinib, an ALK/ROS1 inhibitor, markedly suppressed ALK/ROS1 fusion-positive JMML cell proliferation in vitro.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	55-58
29437595-6	2018	Crizotinib, an ALK/ROS1 inhibitor, markedly suppressed ALK/ROS1 fusion-positive JMML cell proliferation in vitro.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	59-63
29437595-7	2018	Therefore, we administered crizotinib to a chemotherapy-resistant patient with the RANBP2-ALK fusion who subsequently achieved complete molecular remission.	Crizotinib	27-37	RAN binding protein 2	Homo sapiens	83-89
29437595-7	2018	Therefore, we administered crizotinib to a chemotherapy-resistant patient with the RANBP2-ALK fusion who subsequently achieved complete molecular remission.	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	90-93
29437595-11	2018	Crizotinib is a promising candidate drug for the treatment of JMML, particularly in patients with ALK/ROS1 fusions.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	98-101
29437595-11	2018	Crizotinib is a promising candidate drug for the treatment of JMML, particularly in patients with ALK/ROS1 fusions.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	102-106
29420337-0	2018	Anticancer effect of (S)-crizotinib on osteosarcoma cells by targeting MTH1 and activating reactive oxygen species.	Crizotinib	21-35	nudix hydrolase 1	Homo sapiens	71-75
29420337-2	2018	This study aimed to explore the anticancer effect of MTH1-targeted drug (S)-crizotinib on osteosarcoma (OS) cells.	Crizotinib	76-86	nudix hydrolase 1	Homo sapiens	53-57
29420337-5	2018	The anticancer effects of the MTH1-targeted drug (S)-crizotinib on OS cells were explored by in-vitro assays.	Crizotinib	53-63	nudix hydrolase 1	Homo sapiens	30-34
29420337-9	2018	(S)-Crizotinib could inhibit the proliferation of OS cells with an increase in the apoptosis levels and causing G0/G1 arrest by targeting MTH1 and activating ROS.	Crizotinib	0-14	nudix hydrolase 1	Homo sapiens	138-142
29420337-11	2018	(S)-Crizotinib could suppress the proliferation and migration, cause G0/G1 arrest, and increase the apoptosis level of OS cells by targeting MTH1 and activating ROS.	Crizotinib	0-14	nudix hydrolase 1	Homo sapiens	141-145
29862230-3	2018	Crizotinib was the first-in-class ALK TKI with proven superiority over standard platinum-based chemotherapy for the 1st-line therapy of ALK-rearranged NSCLC patients.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	34-37
29862230-3	2018	Crizotinib was the first-in-class ALK TKI with proven superiority over standard platinum-based chemotherapy for the 1st-line therapy of ALK-rearranged NSCLC patients.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	136-139
29862230-4	2018	However, the acquired resistance to crizotinib and its diminished efficacy to the central nervous system (CNS) relapse led to the development of several novel ALK inhibitors, more potent and with different selectivity compared to crizotinib.	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	159-162
29501208-4	2018	The AcSe crizotinib program, supported by the Inca (french Cancer National Institute), is emblematic of a success of this personalized medicine illustrated by 4 points: the discovery of a cohort of patients with lung cancer with a ROS1 rearrangement characteristic of a sensitivity to crizotinib, a rapid availability of this innovation through the implementation of a temporary recommendation for use (ANSM), the obtention of a conditional marketing authorization by the pharmaceutical industry and finally, financial assumption of responsibility by French social security (HAS), despite preliminary and non-comparative data.	Crizotinib	9-19	caspase recruitment domain family member 17	Homo sapiens	46-50
29570930-7	2018	The CSE-treated NSCLC cells are sensitive to the c-MET inhibitor crizotinib.	Crizotinib	65-75	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	49-54
29501208-4	2018	The AcSe crizotinib program, supported by the Inca (french Cancer National Institute), is emblematic of a success of this personalized medicine illustrated by 4 points: the discovery of a cohort of patients with lung cancer with a ROS1 rearrangement characteristic of a sensitivity to crizotinib, a rapid availability of this innovation through the implementation of a temporary recommendation for use (ANSM), the obtention of a conditional marketing authorization by the pharmaceutical industry and finally, financial assumption of responsibility by French social security (HAS), despite preliminary and non-comparative data.	Crizotinib	9-19	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	231-235
29501208-4	2018	The AcSe crizotinib program, supported by the Inca (french Cancer National Institute), is emblematic of a success of this personalized medicine illustrated by 4 points: the discovery of a cohort of patients with lung cancer with a ROS1 rearrangement characteristic of a sensitivity to crizotinib, a rapid availability of this innovation through the implementation of a temporary recommendation for use (ANSM), the obtention of a conditional marketing authorization by the pharmaceutical industry and finally, financial assumption of responsibility by French social security (HAS), despite preliminary and non-comparative data.	Crizotinib	285-295	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	231-235
28675026-2	2018	Both mechanistic target of rapamycin (mTOR) inhibitor everolimus and ALK inhibitor crizotinib have shown promising antitumor activity in ALK-positive cancer cell lines.	Crizotinib	83-93	ALK receptor tyrosine kinase	Homo sapiens	69-72
29610289-4	2018	Data from large-scale genetic screens in molecularly diverse breast tumor cell lines established that the E-cadherin/ROS1 synthetic lethality was not only robust in the face of considerable molecular heterogeneity but was also elicited with clinical ROS1 inhibitors, including foretinib and crizotinib.	Crizotinib	291-301	cadherin 1	Homo sapiens	106-116
28675026-2	2018	Both mechanistic target of rapamycin (mTOR) inhibitor everolimus and ALK inhibitor crizotinib have shown promising antitumor activity in ALK-positive cancer cell lines.	Crizotinib	83-93	ALK receptor tyrosine kinase	Homo sapiens	137-140
28675026-7	2018	Crizotinib down-regulated aberrant AKT and ERK phosphorylation induced by everolimus.	Crizotinib	0-10	AKT serine/threonine kinase 1	Homo sapiens	35-38
28675026-7	2018	Crizotinib down-regulated aberrant AKT and ERK phosphorylation induced by everolimus.	Crizotinib	0-10	mitogen-activated protein kinase 1	Homo sapiens	43-46
28675026-10	2018	The synergistic effect of everolimus and crizotinib was also reproduced in the ALK-positive lung adenocarcinoma cell line NCI-H2228.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	79-82
28675026-12	2018	CONCLUSION: Crizotinib combinedwith everolimus synergistically inhibits proliferation of ALK-positive ALCL cells.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	89-92
29472032-0	2018	Xanthogranulomatous pyelonephritis complicating crizotinib treatment of an ALK-rearranged non-small-cell lung cancer.	Crizotinib	48-58	ALK receptor tyrosine kinase	Homo sapiens	75-78
29610289-4	2018	Data from large-scale genetic screens in molecularly diverse breast tumor cell lines established that the E-cadherin/ROS1 synthetic lethality was not only robust in the face of considerable molecular heterogeneity but was also elicited with clinical ROS1 inhibitors, including foretinib and crizotinib.	Crizotinib	291-301	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	117-121
29610289-7	2018	These data therefore provide the preclinical rationale for assessing ROS1 inhibitors, such as the licensed drug crizotinib, in appropriately stratified patients.Significance: E-cadherin defects are common in breast cancer but are currently not targeted with a precision medicine approach.	Crizotinib	112-122	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	69-73
29610289-7	2018	These data therefore provide the preclinical rationale for assessing ROS1 inhibitors, such as the licensed drug crizotinib, in appropriately stratified patients.Significance: E-cadherin defects are common in breast cancer but are currently not targeted with a precision medicine approach.	Crizotinib	112-122	cadherin 1	Homo sapiens	175-185
29610289-8	2018	Our preclinical data indicate that licensed ROS1 inhibitors, including crizotinib, should be repurposed to target E-cadherin-defective breast cancers, thus providing the rationale for the assessment of these agents in molecularly stratified phase II clinical trials.	Crizotinib	71-81	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	44-48
29128427-0	2018	Osimertinib and Cabozantinib Combinatorial Therapy in an EGFR-Mutant Lung Adenocarcinoma Patient with Multiple MET Secondary-Site Mutations after Resistance to Crizotinib.	Crizotinib	160-170	epidermal growth factor receptor	Homo sapiens	57-61
29622884-0	2018	Refractory ALK-Positive Anaplastic Large Cell Lymphoma: Long Term Survival with Crizotinib.	Crizotinib	80-90	ALK receptor tyrosine kinase	Homo sapiens	11-14
30441974-0	2018	Effects of Treatment with Crizotinib on Non-small Cell Lung Carcinoma with ALK Translocation in the Czech Republic.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	75-78
29576302-0	2018	Appearance of a BRAF Mutation Conferring Resistance to Crizotinib in Non-Small Cell Lung Cancer Harboring Oncogenic ROS1 Fusion.	Crizotinib	55-65	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	16-20
29576302-0	2018	Appearance of a BRAF Mutation Conferring Resistance to Crizotinib in Non-Small Cell Lung Cancer Harboring Oncogenic ROS1 Fusion.	Crizotinib	55-65	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	116-120
29474558-11	2018	Conclusions: Consistent with overall population, ceritinib demonstrated better efficacy compared with the standard second-line chemotherapy in Japanese patients with crizotinib-resistant ALK+ NSCLC.	Crizotinib	166-176	ALK receptor tyrosine kinase	Homo sapiens	187-190
30441974-1	2018	BACKGROUND: Patients with advanced anaplastic lymphoma kinase (ALK) -positive non-small cell lung cancer (NSCLC) may gain significant benefit from treatment with the first-generation ALK inhibitor crizotinib.	Crizotinib	197-207	ALK receptor tyrosine kinase	Homo sapiens	35-61
30441974-1	2018	BACKGROUND: Patients with advanced anaplastic lymphoma kinase (ALK) -positive non-small cell lung cancer (NSCLC) may gain significant benefit from treatment with the first-generation ALK inhibitor crizotinib.	Crizotinib	197-207	ALK receptor tyrosine kinase	Homo sapiens	63-66
30441974-1	2018	BACKGROUND: Patients with advanced anaplastic lymphoma kinase (ALK) -positive non-small cell lung cancer (NSCLC) may gain significant benefit from treatment with the first-generation ALK inhibitor crizotinib.	Crizotinib	197-207	ALK receptor tyrosine kinase	Homo sapiens	183-186
30441974-12	2018	CONCLUSION: Targeted crizotinib therapy is well tolerated and has significant benefit in patients with advanced ALK-positive NSCLC.	Crizotinib	21-31	ALK receptor tyrosine kinase	Homo sapiens	112-115
30441974-15	2018	Key words: ALK translocation - crizotinib - targeted biological therapy - tyrosine kinase inhibitors This work was supported by AZV grant No.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	11-14
29571990-0	2018	Response to crizotinib in advanced ALK-rearranged non-small cell lung cancers with different ALK-fusion variants.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	35-38
29571990-0	2018	Response to crizotinib in advanced ALK-rearranged non-small cell lung cancers with different ALK-fusion variants.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	93-96
29571990-2	2018	NSCLCs with ALK-rearrangement can be effectively treated with crizotinib.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	12-15
29571990-4	2018	This study explored the clinical efficacy of crizotinib in different ALK variants.	Crizotinib	45-55	ALK receptor tyrosine kinase	Homo sapiens	69-72
29571990-6	2018	We retrospectively evaluated the efficacy of crizotinib in different ALK variants.	Crizotinib	45-55	ALK receptor tyrosine kinase	Homo sapiens	69-72
29552141-3	2018	The present study aimed to examine the effects of a combination of Sorafenib and low-dose PF-2341066, a selective c-Met tyrosine kinase inhibitor, on the proliferation, apoptosis and migration of the NSCLC cell line NCI-H1993.	Crizotinib	90-100	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	114-119
29571990-11	2018	After adjusting for other baseline characteristics, EML4-ALK variant 2 was identified as an important factor for a better PFS of crizotinib.	Crizotinib	129-139	EMAP like 4	Homo sapiens	52-56
29571990-11	2018	After adjusting for other baseline characteristics, EML4-ALK variant 2 was identified as an important factor for a better PFS of crizotinib.	Crizotinib	129-139	ALK receptor tyrosine kinase	Homo sapiens	57-60
29550255-4	2018	In HER2E cells, hepatocyte growth factor, a ligand for MET, induced resistance that could be reversed with crizotinib, an inhibitor of MET.	Crizotinib	107-117	erb-b2 receptor tyrosine kinase 2	Mus musculus	3-7
29286567-0	2018	Crizotinib in ALK+ inflammatory myofibroblastic tumors-Current experience and future perspectives.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	14-17
29286567-2	2018	As about 50% of IMT and 100% of EIMS contain activating rearrangements of the anaplastic lymphoma kinase (ALK) gene, targeted kinase inhibition of ALK by compounds such as crizotinib is a potential treatment option.	Crizotinib	172-182	ALK receptor tyrosine kinase	Homo sapiens	78-104
29286567-2	2018	As about 50% of IMT and 100% of EIMS contain activating rearrangements of the anaplastic lymphoma kinase (ALK) gene, targeted kinase inhibition of ALK by compounds such as crizotinib is a potential treatment option.	Crizotinib	172-182	ALK receptor tyrosine kinase	Homo sapiens	106-109
29286567-2	2018	As about 50% of IMT and 100% of EIMS contain activating rearrangements of the anaplastic lymphoma kinase (ALK) gene, targeted kinase inhibition of ALK by compounds such as crizotinib is a potential treatment option.	Crizotinib	172-182	ALK receptor tyrosine kinase	Homo sapiens	147-150
29286567-5	2018	As preliminary data are promising, a prospective study evaluating crizotinib treatment in patients with unresectable/multifocal ALK+ IMT/EIMS is warranted.	Crizotinib	66-76	ALK receptor tyrosine kinase	Homo sapiens	128-131
29488330-6	2018	Most of these ALK fusions in NSCLC patients respond well to the ALK inhibitor, crizotinib.	Crizotinib	79-89	ALK receptor tyrosine kinase	Homo sapiens	14-17
29488330-6	2018	Most of these ALK fusions in NSCLC patients respond well to the ALK inhibitor, crizotinib.	Crizotinib	79-89	ALK receptor tyrosine kinase	Homo sapiens	64-67
29550255-4	2018	In HER2E cells, hepatocyte growth factor, a ligand for MET, induced resistance that could be reversed with crizotinib, an inhibitor of MET.	Crizotinib	107-117	hepatocyte growth factor	Mus musculus	16-40
29284707-4	2018	All 3 patients showed a partial response to crizotinib that effectively inhibits MET and ALK among other kinases.	Crizotinib	44-54	ALK receptor tyrosine kinase	Homo sapiens	89-92
29470986-6	2018	Besides that, HOTAIR shRNA transfection suppressed drug resistance of A549 cells to Crizotinib by more effectively inhibiting cell viability and promoting apoptosis compared with HOTAIR scramble group.	Crizotinib	84-94	HOX transcript antisense RNA	Homo sapiens	14-20
29470986-7	2018	Moreover, silencing of HOTAIR decreased the number of LC3+ puncta and the expression of Beclin1, p-ULK1 and the ratio of LC3 II/I/in Crizotinib treated A549 cells, indicating that silencing of HOTAIR decreased drug resistance of NSCLC cells might through inhibiting autophagy via the ULK1 pathway.	Crizotinib	133-143	HOX transcript antisense RNA	Homo sapiens	23-29
29470986-11	2018	These results supported our conclusion that silencing of HOTAIR decreased drug resistance of NSCLC cells to Crizotinib through inhibition of autophagy via suppressing phosphorylation of ULK1.	Crizotinib	108-118	HOX transcript antisense RNA	Homo sapiens	57-63
29470986-11	2018	These results supported our conclusion that silencing of HOTAIR decreased drug resistance of NSCLC cells to Crizotinib through inhibition of autophagy via suppressing phosphorylation of ULK1.	Crizotinib	108-118	unc-51 like autophagy activating kinase 1	Homo sapiens	186-190
29662531-1	2018	The central nervous system (CNS) is a common site of disease progression in patients with non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK)-rearrangement treated with crizotinib.	Crizotinib	190-200	ALK receptor tyrosine kinase	Homo sapiens	158-161
29662531-4	2018	Three case reports have been published describing six ALK-rearranged NSCLC patients presenting with CBM, all of which were under treatment with crizotinib by the time of CBM diagnosis.	Crizotinib	144-154	ALK receptor tyrosine kinase	Homo sapiens	54-57
29534405-5	2018	In ALK fusion gene (+ ) patients with recurrence or metastasis, crizotinib target therapy was prefered.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	3-6
29534405-12	2018	Compared with conventional chemotherapy, crizotinib can significantly prolong the survival time of patients with ALK fusion gene.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	113-116
29216400-0	2018	Activity and safety of crizotinib in patients with alveolar soft part sarcoma with rearrangement of TFE3: European Organization for Research and Treatment of Cancer (EORTC) phase II trial 90101 "CREATE".	Crizotinib	23-33	transcription factor binding to IGHM enhancer 3	Homo sapiens	100-104
29216400-15	2018	Conclusion: According to European Organization for Research and Treatment of Cancer (EORTC) efficacy criteria for soft tissue sarcoma, our study demonstrated that crizotinib has activity in TFE3 rearranged ASPS MET+ patients.	Crizotinib	163-173	transcription factor binding to IGHM enhancer 3	Homo sapiens	190-194
29102694-0	2018	KIF5B-MET Gene Rearrangement with Robust Antitumor Activity in Response to Crizotinib in Lung Adenocarcinoma.	Crizotinib	75-85	kinesin family member 5B	Homo sapiens	0-5
29256901-3	2018	Since the discovery, development and approval of crizotinib in 2011, three second-generation ALK-TKIs, ceritinib, alectinib and brigatinib have been approved by the FDA.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	93-96
29256901-4	2018	A range of newer generation ALK inhibitors with improved potency against ALK and against mutations that confer resistance to crizotinib are in clinical development.	Crizotinib	125-135	ALK receptor tyrosine kinase	Homo sapiens	28-31
29472060-0	2018	Reporting on Two Novel Fusions, DYSF-ALK and ITGAV-ALK, Coexisting in One Patient with Adenocarcinoma of Lung, Sensitive to Crizotinib.	Crizotinib	124-134	ALK receptor tyrosine kinase	Homo sapiens	51-54
29472060-0	2018	Reporting on Two Novel Fusions, DYSF-ALK and ITGAV-ALK, Coexisting in One Patient with Adenocarcinoma of Lung, Sensitive to Crizotinib.	Crizotinib	124-134	dysferlin	Homo sapiens	32-36
29472060-0	2018	Reporting on Two Novel Fusions, DYSF-ALK and ITGAV-ALK, Coexisting in One Patient with Adenocarcinoma of Lung, Sensitive to Crizotinib.	Crizotinib	124-134	ALK receptor tyrosine kinase	Homo sapiens	37-40
29535535-1	2018	Background: Alectinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor approved by the US Food and Drug Administration to treat crizotinib-refractory non-small cell lung cancer.	Crizotinib	145-155	ALK receptor tyrosine kinase	Homo sapiens	73-76
29456853-0	2018	Crizotinib-associated toxic epidermal necrolysis in an ALK-positive advanced NSCLC patient.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	55-58
29456853-1	2018	Crizotinib is an oral small-molecule inhibitor of anaplastic lymphoma kinase (ALK) tyrosine-kinase that has been approved for treating patients with advanced echinoderm microtubule associated protein like 4-ALK rearranged non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	50-76
29456853-1	2018	Crizotinib is an oral small-molecule inhibitor of anaplastic lymphoma kinase (ALK) tyrosine-kinase that has been approved for treating patients with advanced echinoderm microtubule associated protein like 4-ALK rearranged non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	78-81
29456853-1	2018	Crizotinib is an oral small-molecule inhibitor of anaplastic lymphoma kinase (ALK) tyrosine-kinase that has been approved for treating patients with advanced echinoderm microtubule associated protein like 4-ALK rearranged non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	EMAP like 4	Homo sapiens	158-206
29456853-1	2018	Crizotinib is an oral small-molecule inhibitor of anaplastic lymphoma kinase (ALK) tyrosine-kinase that has been approved for treating patients with advanced echinoderm microtubule associated protein like 4-ALK rearranged non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	207-210
29456853-3	2018	The present study reported a case of a 75-year-old Chinese male patient with advanced NSCLC with ALK fusion, who developed TEN after 56 days of crizotinib treatment and demised due to this dermatological adverse event.	Crizotinib	144-154	ALK receptor tyrosine kinase	Homo sapiens	97-100
29535535-8	2018	ALK inhibitor-naive patients tend to have better responses than crizotinib-pretreated patients.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	0-3
29535535-10	2018	The incidences of most adverse events were relatively low, while the incidences of 2 frequently reported adverse events, myalgia (18%) and anemia (25%), were even higher than with the first-generation ALK inhibitor crizotinib.	Crizotinib	215-225	ALK receptor tyrosine kinase	Homo sapiens	201-204
29535536-0	2018	Response to crizotinib in a non-small-cell lung cancer patient harboring an EML4-ALK fusion with an atypical LTBP1 insertion.	Crizotinib	12-22	EMAP like 4	Homo sapiens	76-80
29535536-0	2018	Response to crizotinib in a non-small-cell lung cancer patient harboring an EML4-ALK fusion with an atypical LTBP1 insertion.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	81-84
29535536-0	2018	Response to crizotinib in a non-small-cell lung cancer patient harboring an EML4-ALK fusion with an atypical LTBP1 insertion.	Crizotinib	12-22	latent transforming growth factor beta binding protein 1	Homo sapiens	109-114
29463284-3	2018	Recently, the outcomes of two independent phase 3 trials regarding Alectinib versus Crizotinib in ALK-positive NSCLC are encouraging.	Crizotinib	84-94	ALK receptor tyrosine kinase	Homo sapiens	98-101
29495603-2	2018	Crizotinib was the first ALK inhibitor to receive FDA approval for ALK-positive NSCLC patients treatment.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	25-28
29495603-2	2018	Crizotinib was the first ALK inhibitor to receive FDA approval for ALK-positive NSCLC patients treatment.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	67-70
29495603-4	2018	Thus, to overcome crizotinib resistance, second/third-generation ALK inhibitors have been developed and received, or are close to receiving, FDA approval.	Crizotinib	18-28	ALK receptor tyrosine kinase	Homo sapiens	65-68
29440379-7	2018	Using this model, we discovered that cMET blockade by crizotinib (CRZ) enhanced schwannoma radiosensitivity by enhancing DNA damage, and CRZ treatment combined with low-dose radiation was as effective as high-dose radiation.	Crizotinib	54-64	met proto-oncogene	Mus musculus	37-41
29440379-7	2018	Using this model, we discovered that cMET blockade by crizotinib (CRZ) enhanced schwannoma radiosensitivity by enhancing DNA damage, and CRZ treatment combined with low-dose radiation was as effective as high-dose radiation.	Crizotinib	66-69	met proto-oncogene	Mus musculus	37-41
29440379-9	2018	This cMET gene knockdown study independently confirmed the role of the cMET pathway in mediating the effect of CRZ.	Crizotinib	111-114	met proto-oncogene	Mus musculus	5-9
29440379-9	2018	This cMET gene knockdown study independently confirmed the role of the cMET pathway in mediating the effect of CRZ.	Crizotinib	111-114	met proto-oncogene	Mus musculus	71-75
29632648-0	2018	Outcomes of ALK positive lung cancer patients treated with crizotinib or second-generation ALK inhibitor: a monoinstitutional experience.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	12-15
29455675-3	2018	Soon after, crizotinib, a small molecule ATP-competitive ALK inhibitor was proven to be more effective than chemotherapy in ALK-positive NSCLC patients.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	57-60
29455675-4	2018	Crizotinib and two other ATP-competitive ALK inhibitors, ceritinib and alectinib, are approved for use as a first-line therapy in these patients, where ALK rearrangement is currently diagnosed by immunohistochemistry and in situ hybridization.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	152-155
29450203-0	2018	Real-life experience of ceritinib in crizotinib-pretreated ALK+ advanced non-small cell lung cancer patients.	Crizotinib	37-47	ALK receptor tyrosine kinase	Homo sapiens	59-62
29450203-1	2018	Here we report our experience of ceritinib in crizotinib-pretreated patients with anaplastic lymphoma kinase (ALK) positive (ALK+) non-small cell lung cancer (NSCLC) in a French temporary authorisation for use (TAU) study.	Crizotinib	46-56	ALK receptor tyrosine kinase	Homo sapiens	82-108
29450203-1	2018	Here we report our experience of ceritinib in crizotinib-pretreated patients with anaplastic lymphoma kinase (ALK) positive (ALK+) non-small cell lung cancer (NSCLC) in a French temporary authorisation for use (TAU) study.	Crizotinib	46-56	ALK receptor tyrosine kinase	Homo sapiens	110-113
29450203-2	2018	The French TAU study included crizotinib-pretreated patients with advanced ALK+ or ROS proto-oncogene 1 positive (ROS1+) tumours.	Crizotinib	30-40	ALK receptor tyrosine kinase	Homo sapiens	75-78
27606884-0	2018	Central retinal artery occlusion, an early sign of crizotinib resistance in an alk positive adenocarcinoma of lung: A rare case report.	Crizotinib	51-61	ALK receptor tyrosine kinase	Homo sapiens	79-82
27606884-2	2018	Crizotinib, the first inhibitor of anaplastic lymphoma kinase (ALK), ROS1 and c-Met receptor kinase, has been used in the treatment of ALK-positive non-small cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	35-61
27606884-2	2018	Crizotinib, the first inhibitor of anaplastic lymphoma kinase (ALK), ROS1 and c-Met receptor kinase, has been used in the treatment of ALK-positive non-small cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	63-66
27606884-2	2018	Crizotinib, the first inhibitor of anaplastic lymphoma kinase (ALK), ROS1 and c-Met receptor kinase, has been used in the treatment of ALK-positive non-small cell lung cancer.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	69-73
27606884-2	2018	Crizotinib, the first inhibitor of anaplastic lymphoma kinase (ALK), ROS1 and c-Met receptor kinase, has been used in the treatment of ALK-positive non-small cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	135-138
29458783-2	2018	Crizotinib was the first ALK inhibitor approved and utilised in the treatment of ALK+ NSCLC patients in the second line setting first and subsequently in the first line one.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	25-28
29458783-2	2018	Crizotinib was the first ALK inhibitor approved and utilised in the treatment of ALK+ NSCLC patients in the second line setting first and subsequently in the first line one.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	81-84
29439172-3	2018	This report describes a 21-year-old woman with an aggressive, metastatic IMT with a novel NUMA1-ALK fusion that showed a dramatic response to the ALK inhibitors crizotinib and alectinib.	Crizotinib	161-171	nuclear mitotic apparatus protein 1	Homo sapiens	90-95
29439172-3	2018	This report describes a 21-year-old woman with an aggressive, metastatic IMT with a novel NUMA1-ALK fusion that showed a dramatic response to the ALK inhibitors crizotinib and alectinib.	Crizotinib	161-171	ALK receptor tyrosine kinase	Homo sapiens	96-99
29439172-3	2018	This report describes a 21-year-old woman with an aggressive, metastatic IMT with a novel NUMA1-ALK fusion that showed a dramatic response to the ALK inhibitors crizotinib and alectinib.	Crizotinib	161-171	ALK receptor tyrosine kinase	Homo sapiens	146-149
29439172-5	2018	The patient"s aggressive IMT responded favorably to crizotinib and alectinib, suggesting that ALK inhibitors may be effective in IMT with NUMA1-ALK fusions.	Crizotinib	52-62	ALK receptor tyrosine kinase	Homo sapiens	94-97
29439172-5	2018	The patient"s aggressive IMT responded favorably to crizotinib and alectinib, suggesting that ALK inhibitors may be effective in IMT with NUMA1-ALK fusions.	Crizotinib	52-62	nuclear mitotic apparatus protein 1	Homo sapiens	138-143
29439172-5	2018	The patient"s aggressive IMT responded favorably to crizotinib and alectinib, suggesting that ALK inhibitors may be effective in IMT with NUMA1-ALK fusions.	Crizotinib	52-62	ALK receptor tyrosine kinase	Homo sapiens	144-147
29413046-0	2018	ALK fusion variants detection by targeted RNA-next generation sequencing and clinical responses to crizotinib in ALK-positive non-small cell lung cancer.	Crizotinib	99-109	ALK receptor tyrosine kinase	Homo sapiens	113-116
29413046-1	2018	OBJECTIVES: The aim of the present study was firstly to assess in a clinical setting the yields of an amplicon-based parallel RNA sequencing (RNA-seq) assay for ALK fusion transcript variants detection in comparison with immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH) in a selected population of ALK-positive and ALK-negative non-small cell lung cancer (NSCLC) cases, and secondly to evaluate the impact of the ALK variant on crizotinib efficacy.	Crizotinib	451-461	ALK receptor tyrosine kinase	Homo sapiens	161-164
29413046-7	2018	When crizotinib efficacy was evaluated according to the type of ALK variant, better clinical outcomes were observed in crizotinib-treated patients with EML4-ALK v1/v2/others variants compared to v3a/b variants.	Crizotinib	5-15	ALK receptor tyrosine kinase	Homo sapiens	64-67
29413046-7	2018	When crizotinib efficacy was evaluated according to the type of ALK variant, better clinical outcomes were observed in crizotinib-treated patients with EML4-ALK v1/v2/others variants compared to v3a/b variants.	Crizotinib	5-15	EMAP like 4	Homo sapiens	152-163
29413046-7	2018	When crizotinib efficacy was evaluated according to the type of ALK variant, better clinical outcomes were observed in crizotinib-treated patients with EML4-ALK v1/v2/others variants compared to v3a/b variants.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	64-67
29413046-7	2018	When crizotinib efficacy was evaluated according to the type of ALK variant, better clinical outcomes were observed in crizotinib-treated patients with EML4-ALK v1/v2/others variants compared to v3a/b variants.	Crizotinib	119-129	EMAP like 4	Homo sapiens	152-163
30263998-0	2018	An anaplastic lymphoma kinase (ALK) fusion oncogene positive metastatic sarcomatoid carcinoma of the lung with good response to crizotinib.	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	3-29
30263998-0	2018	An anaplastic lymphoma kinase (ALK) fusion oncogene positive metastatic sarcomatoid carcinoma of the lung with good response to crizotinib.	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	31-34
30263998-3	2018	We report a case of carcinosarcoma with ALK-EML4 fusion gene in a 50-year-old male patient with a good response to therapy with crizotinib.	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	40-43
30263998-3	2018	We report a case of carcinosarcoma with ALK-EML4 fusion gene in a 50-year-old male patient with a good response to therapy with crizotinib.	Crizotinib	128-138	EMAP like 4	Homo sapiens	44-48
29361925-1	2018	BACKGROUND: Crizotinib is recommended as first-line therapy in ROS1-driven lung adenocarcinoma.	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	63-67
29403310-3	2018	Classically, second-generation ALK inhibitors have been the standard of care in the crizotinib-resistant population; however, each ALK inhibitor has a different spectrum of sensitivity to ALK mutations, complicating the optimal treatment strategy for the resistant population.	Crizotinib	84-94	ALK receptor tyrosine kinase	Homo sapiens	31-34
29403310-3	2018	Classically, second-generation ALK inhibitors have been the standard of care in the crizotinib-resistant population; however, each ALK inhibitor has a different spectrum of sensitivity to ALK mutations, complicating the optimal treatment strategy for the resistant population.	Crizotinib	84-94	ALK receptor tyrosine kinase	Homo sapiens	131-134
29403310-3	2018	Classically, second-generation ALK inhibitors have been the standard of care in the crizotinib-resistant population; however, each ALK inhibitor has a different spectrum of sensitivity to ALK mutations, complicating the optimal treatment strategy for the resistant population.	Crizotinib	84-94	ALK receptor tyrosine kinase	Homo sapiens	131-134
29507657-1	2018	A subset of lung cancers is dependent on the anaplastic lymphoma kinase (ALK) oncogene for survival, a mechanism that is exploited by the use of the ALK inhibitor crizotinib.	Crizotinib	163-173	ALK receptor tyrosine kinase	Homo sapiens	45-71
29507657-1	2018	A subset of lung cancers is dependent on the anaplastic lymphoma kinase (ALK) oncogene for survival, a mechanism that is exploited by the use of the ALK inhibitor crizotinib.	Crizotinib	163-173	ALK receptor tyrosine kinase	Homo sapiens	73-76
29507657-1	2018	A subset of lung cancers is dependent on the anaplastic lymphoma kinase (ALK) oncogene for survival, a mechanism that is exploited by the use of the ALK inhibitor crizotinib.	Crizotinib	163-173	ALK receptor tyrosine kinase	Homo sapiens	149-152
29507657-2	2018	Despite exceptional initial tumor responses to ALK inhibition by crizotinib, durable clinical response is limited and the emergence of drug resistance occurs.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	47-50
29507657-5	2018	Using a loss-of-function whole genome short-hairpin (shRNA) screen, we identified MYCBP as a determinant of response to crizotinib, implicating the MYC signaling axis in resistance to crizotinib-treated ALK+ NSCLC.	Crizotinib	120-130	MYC binding protein	Homo sapiens	82-87
29507657-5	2018	Using a loss-of-function whole genome short-hairpin (shRNA) screen, we identified MYCBP as a determinant of response to crizotinib, implicating the MYC signaling axis in resistance to crizotinib-treated ALK+ NSCLC.	Crizotinib	120-130	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	82-85
29507657-5	2018	Using a loss-of-function whole genome short-hairpin (shRNA) screen, we identified MYCBP as a determinant of response to crizotinib, implicating the MYC signaling axis in resistance to crizotinib-treated ALK+ NSCLC.	Crizotinib	184-194	MYC binding protein	Homo sapiens	82-87
29507657-5	2018	Using a loss-of-function whole genome short-hairpin (shRNA) screen, we identified MYCBP as a determinant of response to crizotinib, implicating the MYC signaling axis in resistance to crizotinib-treated ALK+ NSCLC.	Crizotinib	184-194	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	82-85
29507657-7	2018	Inhibition of MYC by RNAi or small molecules sensitizes ALK+ cells to crizotinib.	Crizotinib	70-80	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	14-17
29507657-7	2018	Inhibition of MYC by RNAi or small molecules sensitizes ALK+ cells to crizotinib.	Crizotinib	70-80	ALK receptor tyrosine kinase	Homo sapiens	56-59
29371790-9	2018	By then, the patient was started with crizotinib 250 mg twice daily for ROS1 mutation in July 2016.	Crizotinib	38-48	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	72-76
29371790-12	2018	Crizotinib was approved on March 11, 2016 by Food and Drug Administration for the treatment of patients with ROS1-positive NSCLC.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	109-113
29371790-13	2018	Conclusions: In this report, crizotinib showed marked antitumor activity in patients with advanced ROS1 rearrangement, a third molecular subgroup of NSCLC.	Crizotinib	29-39	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	99-103
29300322-0	2018	Mutations in EMT-Related Genes in ALK Positive Crizotinib Resistant Non-Small Cell Lung Cancers.	Crizotinib	47-57	ALK receptor tyrosine kinase	Homo sapiens	34-37
29300322-1	2018	Crizotinib is an effective drug for patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), but upon treatment, the tumors inevitably become crizotinib resistant in time.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	50-76
29300322-1	2018	Crizotinib is an effective drug for patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), but upon treatment, the tumors inevitably become crizotinib resistant in time.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	78-81
29304828-2	2018	TAE684 is a potent second generation ALK inhibitor that overcomes Crizotinib resistance.	Crizotinib	66-76	ALK receptor tyrosine kinase	Homo sapiens	37-40
29298713-0	2018	Crizotinib in patients with anaplastic lymphoma kinase-positive advanced non-small cell lung cancer versus chemotherapy as a first-line treatment.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	28-54
29298713-1	2018	BACKGROUND: To compare the efficacy of crizotinib, pemetrexed and other chemotherapy regimens as a first-line treatment in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in real world clinical use and to evaluate the +86-571-87,236,876 predictive clinical factors of the efficacy of crizotinib.	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	137-163
29298713-1	2018	BACKGROUND: To compare the efficacy of crizotinib, pemetrexed and other chemotherapy regimens as a first-line treatment in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in real world clinical use and to evaluate the +86-571-87,236,876 predictive clinical factors of the efficacy of crizotinib.	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	165-168
29298713-10	2018	CONCLUSIONS: In patients with ALK-positive NSCLC who did not receive previous treatment, crizotinib was superior to standard chemotherapy for the longer PFS and greater ORR and DCR.	Crizotinib	89-99	ALK receptor tyrosine kinase	Homo sapiens	30-33
30144837-6	2018	For predicting response to crizotinib, testing for ALK and ROS1 gene rearrangement is necessary.	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	51-54
30144837-6	2018	For predicting response to crizotinib, testing for ALK and ROS1 gene rearrangement is necessary.	Crizotinib	27-37	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	59-63
29150811-0	2018	ALK expression plays different roles in anaplastic large-cell lymphomas and outcome of crizotinib use in relapsed/refractory ALK+ patients in a Chinese population.	Crizotinib	87-97	ALK receptor tyrosine kinase	Homo sapiens	0-3
29150811-0	2018	ALK expression plays different roles in anaplastic large-cell lymphomas and outcome of crizotinib use in relapsed/refractory ALK+ patients in a Chinese population.	Crizotinib	87-97	ALK receptor tyrosine kinase	Homo sapiens	125-128
29150811-4	2018	We evaluated the incidence of ALCL, clinical characteristics, survival status, and outcome of crizotinib use in four relapsed/refractory ALK-positive patients.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	137-140
29150811-13	2018	Four relapsed ALK-positive patients were treated with crizotinib and two died.	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	14-17
30095326-8	2018	We report here the first patient with co-existing ROS1 fusion and de-novo MET amplification to receive crizotinib in China.	Crizotinib	103-113	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	50-54
29300322-4	2018	Four ALK positive patients with progressive disease following crizotinib treatment were identified with paired pre- and post-crizotinib tumor tissue from our previously published cohort.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	5-8
29300322-4	2018	Four ALK positive patients with progressive disease following crizotinib treatment were identified with paired pre- and post-crizotinib tumor tissue from our previously published cohort.	Crizotinib	125-135	ALK receptor tyrosine kinase	Homo sapiens	5-8
28844392-0	2018	Lazarus Syndrome With Crizotinib in a Non-Small Cell Lung Cancer Patient With ROS1 Rearrangement and Disseminated Intravascular Coagulation.	Crizotinib	22-32	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	78-82
29187012-10	2018	Further research will clarify the best management of ALK-positive NSCLC, above all who progress on first-line crizotinib.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	53-56
29758320-0	2018	Neoadjuvant crizotinib in ALK-rearranged inflammatory myofibroblastic tumor of the urinary bladder: A case report.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	26-29
29758320-2	2018	Given that approximately half of all IMT cases have anaplastic lymphoma kinase (ALK) rearrangements, the ALK inhibitor crizotinib is suggested as a promising treatment for unresectable cases.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	52-78
29758320-2	2018	Given that approximately half of all IMT cases have anaplastic lymphoma kinase (ALK) rearrangements, the ALK inhibitor crizotinib is suggested as a promising treatment for unresectable cases.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	80-83
29758320-2	2018	Given that approximately half of all IMT cases have anaplastic lymphoma kinase (ALK) rearrangements, the ALK inhibitor crizotinib is suggested as a promising treatment for unresectable cases.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	105-108
30564472-2	2018	Anaplastic lymphoma kinase (ALK) mutations are present in about 5% of NSCLC cases, and treatment with the first-generation ALK inhibitor crizotinib has shown better progression-free survival (PFS) and response rate compared to traditional chemotherapy.	Crizotinib	137-147	ALK receptor tyrosine kinase	Homo sapiens	0-26
30564472-2	2018	Anaplastic lymphoma kinase (ALK) mutations are present in about 5% of NSCLC cases, and treatment with the first-generation ALK inhibitor crizotinib has shown better progression-free survival (PFS) and response rate compared to traditional chemotherapy.	Crizotinib	137-147	ALK receptor tyrosine kinase	Homo sapiens	28-31
30564472-2	2018	Anaplastic lymphoma kinase (ALK) mutations are present in about 5% of NSCLC cases, and treatment with the first-generation ALK inhibitor crizotinib has shown better progression-free survival (PFS) and response rate compared to traditional chemotherapy.	Crizotinib	137-147	ALK receptor tyrosine kinase	Homo sapiens	123-126
30564472-3	2018	However, eventually, ALK-mutated NSCLC develops resistance to treatment with crizotinib, and second-generation ALK inhibitors such as ceritinib, brigatinib, and alectinib have been shown to be effective in the second-line setting after progression on crizotinib.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	21-24
30564472-3	2018	However, eventually, ALK-mutated NSCLC develops resistance to treatment with crizotinib, and second-generation ALK inhibitors such as ceritinib, brigatinib, and alectinib have been shown to be effective in the second-line setting after progression on crizotinib.	Crizotinib	251-261	ALK receptor tyrosine kinase	Homo sapiens	21-24
30564472-3	2018	However, eventually, ALK-mutated NSCLC develops resistance to treatment with crizotinib, and second-generation ALK inhibitors such as ceritinib, brigatinib, and alectinib have been shown to be effective in the second-line setting after progression on crizotinib.	Crizotinib	251-261	ALK receptor tyrosine kinase	Homo sapiens	111-114
29290262-6	2018	The activation of downstream signaling pathways of ALK and their responses to crizotinib inhibition were studied in HEK-293 and 293T cells with ectopic expression of GCC2-ALK.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	51-54
29505507-4	2018	Here, we reported 2 lung adenocarcinoma cases with MET amplification in pleural effusion rapidly responded to crizotinib after EGFR-TKIs acquired resistance.	Crizotinib	110-120	epidermal growth factor receptor	Homo sapiens	127-131
29505507-10	2018	CONCLUSION: MET amplification in pleural effusion could predict a perfect response to crizotinib after EGFR-TKIs acquired resistance, even only a low times gene amplification.	Crizotinib	86-96	epidermal growth factor receptor	Homo sapiens	103-107
29405994-14	2018	This may have a crucial importance for metastatic patients treatment since ALK rearrangements confer sensitivity to tyrosine kinases inhibitors such as crizotinib.	Crizotinib	152-162	ALK receptor tyrosine kinase	Homo sapiens	75-78
27879019-2	2018	ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, alectinib and ceritinib showed efficiency in patients with primary NSCLC harboring ALK gene rearrangement.	Crizotinib	46-56	ALK receptor tyrosine kinase	Homo sapiens	0-3
27879019-2	2018	ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, alectinib and ceritinib showed efficiency in patients with primary NSCLC harboring ALK gene rearrangement.	Crizotinib	46-56	ALK receptor tyrosine kinase	Homo sapiens	141-144
30207282-0	2018	Benefit of crizotinib in a lung cancer patient with discordant ALK testing results.	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	63-66
30207282-1	2018	Crizotinib is a first line treatment for patients with non-small cell lung cancer (NSCLC) harboring translocations in anaplastic lymphoma kinase (ALK).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	118-144
30207282-1	2018	Crizotinib is a first line treatment for patients with non-small cell lung cancer (NSCLC) harboring translocations in anaplastic lymphoma kinase (ALK).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	146-149
30207282-13	2018	This case illustrates a sustained response to crizotinib therapy in a patient with an ALK translocation identified by IHC, but with negative FISH testing.	Crizotinib	46-56	ALK receptor tyrosine kinase	Homo sapiens	86-89
30273505-0	2018	CMTR1-ALK: an ALK fusion in a patient with no response to ALK inhibitor crizotinib.	Crizotinib	72-82	ALK receptor tyrosine kinase	Homo sapiens	14-17
30273505-0	2018	CMTR1-ALK: an ALK fusion in a patient with no response to ALK inhibitor crizotinib.	Crizotinib	72-82	ALK receptor tyrosine kinase	Homo sapiens	14-17
30273505-3	2018	Most of these ALK fusions responded well to the ALK inhibitor crizotinib.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	14-17
30273505-3	2018	Most of these ALK fusions responded well to the ALK inhibitor crizotinib.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	48-51
30273505-4	2018	Crizotinib is an oral MET/ALK inhibitor used as first-line therapy in the treatment of advanced NSCLC harboring ALK rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	26-29
30273505-4	2018	Crizotinib is an oral MET/ALK inhibitor used as first-line therapy in the treatment of advanced NSCLC harboring ALK rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	112-115
30273505-7	2018	Here, we report the newly found ALK fusion, CMTR1-ALK, in a patient who has no response to the ALK inhibitor crizotinib.	Crizotinib	109-119	ALK receptor tyrosine kinase	Homo sapiens	32-35
30273505-7	2018	Here, we report the newly found ALK fusion, CMTR1-ALK, in a patient who has no response to the ALK inhibitor crizotinib.	Crizotinib	109-119	cap methyltransferase 1	Homo sapiens	44-49
30273505-7	2018	Here, we report the newly found ALK fusion, CMTR1-ALK, in a patient who has no response to the ALK inhibitor crizotinib.	Crizotinib	109-119	ALK receptor tyrosine kinase	Homo sapiens	50-53
30273505-7	2018	Here, we report the newly found ALK fusion, CMTR1-ALK, in a patient who has no response to the ALK inhibitor crizotinib.	Crizotinib	109-119	ALK receptor tyrosine kinase	Homo sapiens	50-53
29187012-4	2018	Areas covered: Crizotinib, the first-in-class ALK/ROS1/MET inhibitor, was initially approved as second-line treatment of ALK-positive advanced NSCLC but after this, it was firmly established as the standard first-line therapy for advanced ALK-positive NSCLC.	Crizotinib	15-25	ALK receptor tyrosine kinase	Homo sapiens	46-49
29187012-4	2018	Areas covered: Crizotinib, the first-in-class ALK/ROS1/MET inhibitor, was initially approved as second-line treatment of ALK-positive advanced NSCLC but after this, it was firmly established as the standard first-line therapy for advanced ALK-positive NSCLC.	Crizotinib	15-25	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	50-54
29187012-4	2018	Areas covered: Crizotinib, the first-in-class ALK/ROS1/MET inhibitor, was initially approved as second-line treatment of ALK-positive advanced NSCLC but after this, it was firmly established as the standard first-line therapy for advanced ALK-positive NSCLC.	Crizotinib	15-25	ALK receptor tyrosine kinase	Homo sapiens	121-124
29187012-4	2018	Areas covered: Crizotinib, the first-in-class ALK/ROS1/MET inhibitor, was initially approved as second-line treatment of ALK-positive advanced NSCLC but after this, it was firmly established as the standard first-line therapy for advanced ALK-positive NSCLC.	Crizotinib	15-25	ALK receptor tyrosine kinase	Homo sapiens	121-124
29187012-6	2018	Next-generation ALK inhibitors, more potent and brain-penetrable than crizotinib, may be effective in re-inducing remissions when cancers are still addicted to ALK.	Crizotinib	70-80	ALK receptor tyrosine kinase	Homo sapiens	16-19
29187012-8	2018	Regarding ROS1 rearrangement, to date crizotinib is the only ALK-tyrosine kinase inhibitor receiving indication as treatment of ROS1 positive advanced NSCLC.	Crizotinib	38-48	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	10-14
29187012-8	2018	Regarding ROS1 rearrangement, to date crizotinib is the only ALK-tyrosine kinase inhibitor receiving indication as treatment of ROS1 positive advanced NSCLC.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	61-64
29187012-8	2018	Regarding ROS1 rearrangement, to date crizotinib is the only ALK-tyrosine kinase inhibitor receiving indication as treatment of ROS1 positive advanced NSCLC.	Crizotinib	38-48	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	128-132
29290262-9	2018	Ectopic expression of GCC2-ALK leads to hyper-activation of ALK downstream signaling that can be inhibited by crizotinib.	Crizotinib	110-120	GRIP and coiled-coil domain containing 2	Homo sapiens	22-26
29290262-9	2018	Ectopic expression of GCC2-ALK leads to hyper-activation of ALK downstream signaling that can be inhibited by crizotinib.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	27-30
29290262-9	2018	Ectopic expression of GCC2-ALK leads to hyper-activation of ALK downstream signaling that can be inhibited by crizotinib.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	60-63
29290262-14	2018	The patient was benefited from crizotinib treatment initially and then ceritinib after progression, suggesting GCC2-ALK as a novel therapeutic target for ALK inhibitors.	Crizotinib	31-41	GRIP and coiled-coil domain containing 2	Homo sapiens	111-115
29290262-14	2018	The patient was benefited from crizotinib treatment initially and then ceritinib after progression, suggesting GCC2-ALK as a novel therapeutic target for ALK inhibitors.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	116-119
29290262-14	2018	The patient was benefited from crizotinib treatment initially and then ceritinib after progression, suggesting GCC2-ALK as a novel therapeutic target for ALK inhibitors.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	154-157
30526220-1	2018	Anaplastic lymphoma kinase (ALK) inhibitors such as crizotinib and alectinib have been shown to have significant activity in ALK-rearranged non-small cell lung cancers (NSCLC).	Crizotinib	52-62	ALK receptor tyrosine kinase	Homo sapiens	0-26
30526220-1	2018	Anaplastic lymphoma kinase (ALK) inhibitors such as crizotinib and alectinib have been shown to have significant activity in ALK-rearranged non-small cell lung cancers (NSCLC).	Crizotinib	52-62	ALK receptor tyrosine kinase	Homo sapiens	28-31
30526220-1	2018	Anaplastic lymphoma kinase (ALK) inhibitors such as crizotinib and alectinib have been shown to have significant activity in ALK-rearranged non-small cell lung cancers (NSCLC).	Crizotinib	52-62	ALK receptor tyrosine kinase	Homo sapiens	125-128
29600239-0	2018	Clinical outcome study of crizotinib in immunohistochemistry-proven echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene among Indian patients with adenocarcinoma lung.	Crizotinib	26-36	EMAP like 4	Homo sapiens	68-116
29600239-2	2018	The aim of this study was to assess the efficacy and safety of twice daily crizotinib tablet (250 mg) in IHC-proven echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene among Indian patients with adenocarcinoma lung in the routine clinical practice.	Crizotinib	75-85	EMAP like 4	Homo sapiens	116-164
29600239-2	2018	The aim of this study was to assess the efficacy and safety of twice daily crizotinib tablet (250 mg) in IHC-proven echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene among Indian patients with adenocarcinoma lung in the routine clinical practice.	Crizotinib	75-85	EMAP like 4	Homo sapiens	166-170
29600239-2	2018	The aim of this study was to assess the efficacy and safety of twice daily crizotinib tablet (250 mg) in IHC-proven echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene among Indian patients with adenocarcinoma lung in the routine clinical practice.	Crizotinib	75-85	ALK receptor tyrosine kinase	Homo sapiens	172-175
29600239-12	2018	Conclusions: A very high PR, PFS, and OS achieved in our study population indicates that IHC can accurately identify EML4 ALK fusion gene mutations in lung adenocarcinoma patients who are responsive to ALK inhibitors such as crizotinib.	Crizotinib	225-235	EMAP like 4	Homo sapiens	117-121
29600239-12	2018	Conclusions: A very high PR, PFS, and OS achieved in our study population indicates that IHC can accurately identify EML4 ALK fusion gene mutations in lung adenocarcinoma patients who are responsive to ALK inhibitors such as crizotinib.	Crizotinib	225-235	ALK receptor tyrosine kinase	Homo sapiens	122-125
29600239-12	2018	Conclusions: A very high PR, PFS, and OS achieved in our study population indicates that IHC can accurately identify EML4 ALK fusion gene mutations in lung adenocarcinoma patients who are responsive to ALK inhibitors such as crizotinib.	Crizotinib	225-235	ALK receptor tyrosine kinase	Homo sapiens	202-205
30095326-10	2018	Advanced or metastatic NSCLC patients with co-existing ROS1 fusion and de-novo MET amplification are sensitive to crizotinib.	Crizotinib	114-124	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	55-59
29203817-0	2017	High expression of beta-catenin contributes to the crizotinib resistant phenotype in the stem-like cell population in neuroblastoma.	Crizotinib	51-61	catenin beta 1	Homo sapiens	19-31
28005438-0	2018	Interactions of crizotinib and gefitinib with organic anion-transporting polypeptides (OATP)1B1, OATP1B3 and OATP2B1: gefitinib shows contradictory interaction with OATP1B3.	Crizotinib	16-26	solute carrier organic anion transporter family member 1B1	Homo sapiens	87-95
28005438-0	2018	Interactions of crizotinib and gefitinib with organic anion-transporting polypeptides (OATP)1B1, OATP1B3 and OATP2B1: gefitinib shows contradictory interaction with OATP1B3.	Crizotinib	16-26	solute carrier organic anion transporter family member 1B3	Homo sapiens	97-104
28005438-0	2018	Interactions of crizotinib and gefitinib with organic anion-transporting polypeptides (OATP)1B1, OATP1B3 and OATP2B1: gefitinib shows contradictory interaction with OATP1B3.	Crizotinib	16-26	solute carrier organic anion transporter family member 2B1	Homo sapiens	109-116
28005438-0	2018	Interactions of crizotinib and gefitinib with organic anion-transporting polypeptides (OATP)1B1, OATP1B3 and OATP2B1: gefitinib shows contradictory interaction with OATP1B3.	Crizotinib	16-26	solute carrier organic anion transporter family member 1B3	Homo sapiens	165-172
28005438-10	2018	OATP1B3- and OATP2B1-mediated crizotinib uptake and OATP2B1-mediated gefitinib uptake were observed.	Crizotinib	30-40	solute carrier organic anion transporter family member 1B3	Homo sapiens	0-7
28005438-10	2018	OATP1B3- and OATP2B1-mediated crizotinib uptake and OATP2B1-mediated gefitinib uptake were observed.	Crizotinib	30-40	solute carrier organic anion transporter family member 2B1	Homo sapiens	13-20
29343973-0	2018	A patient with classic biphasic pulmonary blastoma harboring CD74-ROS1 fusion responds to crizotinib.	Crizotinib	90-100	CD74 molecule	Homo sapiens	61-65
29343973-0	2018	A patient with classic biphasic pulmonary blastoma harboring CD74-ROS1 fusion responds to crizotinib.	Crizotinib	90-100	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	66-70
29343973-5	2018	It has been reported that ROS1 rearranged lung adenocarcinoma and squamous cell carcinoma are sensitive to crizotinib, an ALK/MET/ ROS1 multitargeted tyrosine kinase inhibitor.	Crizotinib	107-117	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	26-30
29343973-5	2018	It has been reported that ROS1 rearranged lung adenocarcinoma and squamous cell carcinoma are sensitive to crizotinib, an ALK/MET/ ROS1 multitargeted tyrosine kinase inhibitor.	Crizotinib	107-117	ALK receptor tyrosine kinase	Homo sapiens	122-125
29343973-5	2018	It has been reported that ROS1 rearranged lung adenocarcinoma and squamous cell carcinoma are sensitive to crizotinib, an ALK/MET/ ROS1 multitargeted tyrosine kinase inhibitor.	Crizotinib	107-117	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	131-135
29343973-8	2018	We report the first clinical evidence of efficacy shown by crizotinib for targeting CD74-ROS1 fusion in CBPB.	Crizotinib	59-69	CD74 molecule	Homo sapiens	84-88
29343973-8	2018	We report the first clinical evidence of efficacy shown by crizotinib for targeting CD74-ROS1 fusion in CBPB.	Crizotinib	59-69	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	89-93
29203817-2	2017	We recently published that the crizotinib sensitivity in NB cells strongly correlates with the crizotinib-ALK binding, and beta-catenin effectively hinders this interaction and confers crizotinib resistance.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	106-109
29203817-2	2017	We recently published that the crizotinib sensitivity in NB cells strongly correlates with the crizotinib-ALK binding, and beta-catenin effectively hinders this interaction and confers crizotinib resistance.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	106-109
29203817-2	2017	We recently published that the crizotinib sensitivity in NB cells strongly correlates with the crizotinib-ALK binding, and beta-catenin effectively hinders this interaction and confers crizotinib resistance.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	106-109
29203817-5	2017	Using the cellular thermal shift assay, we found that RR cells exhibited significantly weaker crizotinib-ALK binding and higher crizotinib resistance than RU cells.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	105-108
29203817-1	2017	ALK has been identified as a novel therapeutic target in neuroblastoma (NB), but resistance to ALK inhibitors (such as crizotinib) is well recognized.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	95-98
29203817-6	2017	The suboptimal crizotinib-ALK binding in RR cells can be attributed to their high beta-catenin expression, since siRNA knockdown of beta-catenin restored the crizotinib-ALK binding and lowered the crizotinib resistance to the level of RU cells.	Crizotinib	15-25	ALK receptor tyrosine kinase	Homo sapiens	26-29
29383132-0	2017	Norcantharidin alone or in combination with crizotinib induces autophagic cell death in hepatocellular carcinoma by repressing c-Met-mTOR signaling.	Crizotinib	44-54	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	127-132
29203817-6	2017	The suboptimal crizotinib-ALK binding in RR cells can be attributed to their high beta-catenin expression, since siRNA knockdown of beta-catenin restored the crizotinib-ALK binding and lowered the crizotinib resistance to the level of RU cells.	Crizotinib	15-25	catenin beta 1	Homo sapiens	132-144
29203817-6	2017	The suboptimal crizotinib-ALK binding in RR cells can be attributed to their high beta-catenin expression, since siRNA knockdown of beta-catenin restored the crizotinib-ALK binding and lowered the crizotinib resistance to the level of RU cells.	Crizotinib	158-168	catenin beta 1	Homo sapiens	132-144
29203817-6	2017	The suboptimal crizotinib-ALK binding in RR cells can be attributed to their high beta-catenin expression, since siRNA knockdown of beta-catenin restored the crizotinib-ALK binding and lowered the crizotinib resistance to the level of RU cells.	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	169-172
29203817-6	2017	The suboptimal crizotinib-ALK binding in RR cells can be attributed to their high beta-catenin expression, since siRNA knockdown of beta-catenin restored the crizotinib-ALK binding and lowered the crizotinib resistance to the level of RU cells.	Crizotinib	158-168	catenin beta 1	Homo sapiens	132-144
29203817-6	2017	The suboptimal crizotinib-ALK binding in RR cells can be attributed to their high beta-catenin expression, since siRNA knockdown of beta-catenin restored the crizotinib-ALK binding and lowered the crizotinib resistance to the level of RU cells.	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	169-172
29203817-8	2017	To conclude, high expression of beta-catenin in the stem-like NB cells contributes to their crizotinib resistance.	Crizotinib	92-102	catenin beta 1	Homo sapiens	32-44
28971587-4	2018	Herein, we report a case of a 42-year-old man diagnosed with lung adenocarcinoma positive for a SDC4-ROS1 fusion, who was treated with crizotinib followed by three cycles of chemotherapy.	Crizotinib	135-145	syndecan 4	Homo sapiens	96-100
28971587-4	2018	Herein, we report a case of a 42-year-old man diagnosed with lung adenocarcinoma positive for a SDC4-ROS1 fusion, who was treated with crizotinib followed by three cycles of chemotherapy.	Crizotinib	135-145	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	101-105
29383132-0	2017	Norcantharidin alone or in combination with crizotinib induces autophagic cell death in hepatocellular carcinoma by repressing c-Met-mTOR signaling.	Crizotinib	44-54	mechanistic target of rapamycin kinase	Homo sapiens	133-137
29383132-4	2017	Moreover, a significant attenuation of tumor growth was observed after NCTD treatment of HepG2 tumors in vivo, and this effect was enhanced by co-treatment with the c-Met inhibitor crizotinib.	Crizotinib	181-191	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	165-170
29383132-6	2017	These results suggest that cytotoxic autophagy resulting from inhibition of c-Met/mTOR signaling may be achieved in HCC by combined NCTD and crizotinib administration.	Crizotinib	141-151	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	76-81
29383132-6	2017	These results suggest that cytotoxic autophagy resulting from inhibition of c-Met/mTOR signaling may be achieved in HCC by combined NCTD and crizotinib administration.	Crizotinib	141-151	mechanistic target of rapamycin kinase	Homo sapiens	82-86
29125233-6	2017	Moreover, HGF stimulated the proliferation of NUGC4 cells, that was inhibited by crizotinib, which has anti-MET activity.	Crizotinib	81-91	hepatocyte growth factor	Homo sapiens	10-13
29125233-7	2017	KM12SM cells were sensitive to the tropomyosin-related kinase-A inhibitors crizotinib and entrectinib.	Crizotinib	75-85	neurotrophic receptor tyrosine kinase 1	Homo sapiens	35-63
28891712-2	2017	Despite high rate of responses, the vast majority of patients treated with first-generation ALK inhibitor crizotinib will ultimately develop disease progression.	Crizotinib	106-116	ALK receptor tyrosine kinase	Homo sapiens	92-95
28891712-3	2017	The second-generation ALK inhibitor, ceritinib, is an oral, small-molecule that inhibits the ALK kinase activity with a potency 20-fold greater than crizotinib, being able to tackle some of the principal mechanisms of resistance to crizotinib.	Crizotinib	149-159	ALK receptor tyrosine kinase	Homo sapiens	22-25
28891712-3	2017	The second-generation ALK inhibitor, ceritinib, is an oral, small-molecule that inhibits the ALK kinase activity with a potency 20-fold greater than crizotinib, being able to tackle some of the principal mechanisms of resistance to crizotinib.	Crizotinib	232-242	ALK receptor tyrosine kinase	Homo sapiens	22-25
28819999-8	2017	HGF-independent Met phosphorylation was prevented by inhibition of integrin alpha5beta1, Met inhibitor crizotinib, Src inhibitors PP2 and SU5565, but not by EGFR inhibitor AG1478.	Crizotinib	103-113	hepatocyte growth factor	Homo sapiens	0-3
29021430-2	2017	The patient was treated with crizotinib after echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangement was detected from his pleural effusion.	Crizotinib	29-39	EMAP like 4	Homo sapiens	46-94
29021430-2	2017	The patient was treated with crizotinib after echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangement was detected from his pleural effusion.	Crizotinib	29-39	EMAP like 4	Homo sapiens	96-100
28903995-4	2017	The small molecule tyrosine kinase inhibitor, crizotinib has been shown to be an effective inhibitor of ROS1 and has received Food and Drug Administration approval for treatment of advanced NSCLC.	Crizotinib	46-56	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	104-108
28819999-9	2017	High glucose increased the expression of TGFbeta-1, CTGF and the tubular damage marker KIM-1 and increased apoptosis of HK2 cells, effects inhibited by crizotinib.	Crizotinib	152-162	cellular communication network factor 2	Homo sapiens	52-56
28819999-9	2017	High glucose increased the expression of TGFbeta-1, CTGF and the tubular damage marker KIM-1 and increased apoptosis of HK2 cells, effects inhibited by crizotinib.	Crizotinib	152-162	hepatitis A virus cellular receptor 1	Homo sapiens	87-92
28911956-0	2017	ALK and ROS1 Double-Rearranged Lung Squamous Cell Carcinoma Responding to Crizotinib Treatment: A Case Report.	Crizotinib	74-84	ALK receptor tyrosine kinase	Homo sapiens	0-3
28911956-0	2017	ALK and ROS1 Double-Rearranged Lung Squamous Cell Carcinoma Responding to Crizotinib Treatment: A Case Report.	Crizotinib	74-84	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	8-12
29074098-16	2017	In ROS1-positive patients, including seven crizotinib-pretreated patients, an objective response was achieved by six (50%) of 12 patients (95% CI 21-79).	Crizotinib	43-53	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	3-7
29091425-2	2017	Secondary mutations opposing activity of the first-generation ALK inhibitor crizotinib came into existence, requiring mutation-targeting drug discovery for the powerful second-line treatment.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	62-65
29079636-12	2017	Patients whose tumors harbor ALK rearrangements or fusions respond to treatment with crizotinib and alectinib, including tumors not normally associated with ALK mutations, such as non-Langerhans cell histiocytosis or renal cell carcinoma.	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	29-32
28856564-3	2017	Crizotinib was the first agent approved for front-line therapy of ALK-rearranged NSCLC after it demonstrated superiority to chemotherapy in response rate, duration of response, and progression-free survival.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	66-69
29091425-3	2017	In this study, we report 4-phenoxyquinoline-based inhibitors that overcome crizotinib resistance to ALK L1196M, discovered by the fragment-growing strategy.	Crizotinib	75-85	ALK receptor tyrosine kinase	Homo sapiens	100-103
29091425-6	2017	The inhibitors exhibited significant antiproliferative effects on H2228 CR crizotinib-resistant cells by decreasing PI3K/AKT and MAPK signaling.	Crizotinib	75-85	AKT serine/threonine kinase 1	Homo sapiens	121-124
28601386-0	2017	Detection of ALK and KRAS Mutations in Circulating Tumor DNA of Patients With Advanced ALK-Positive NSCLC With Disease Progression During Crizotinib Treatment.	Crizotinib	138-148	ALK receptor tyrosine kinase	Homo sapiens	13-16
29167003-7	2017	The median survival time of 58 patients with ALK positive was 15.5 mo (95%CI: 10.991-20.009), and treatment with crizotinib (P=0.022) was the independent influence factor for the survival of ALK positive patients.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	45-48
29167003-7	2017	The median survival time of 58 patients with ALK positive was 15.5 mo (95%CI: 10.991-20.009), and treatment with crizotinib (P=0.022) was the independent influence factor for the survival of ALK positive patients.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	191-194
28855353-8	2017	Presence of these complexes correlated with response to crizotinib in one patient with Deltaexon14 MET lacking MET gene amplification.Conclusions: Proximity assays measuring MET-GRB2 signaling complexes provide novel insights into MET-mediated signaling and could complement current clinical genomics-based assay platforms.	Crizotinib	56-66	growth factor receptor bound protein 2	Homo sapiens	178-182
28601386-0	2017	Detection of ALK and KRAS Mutations in Circulating Tumor DNA of Patients With Advanced ALK-Positive NSCLC With Disease Progression During Crizotinib Treatment.	Crizotinib	138-148	KRAS proto-oncogene, GTPase	Homo sapiens	21-25
28601386-0	2017	Detection of ALK and KRAS Mutations in Circulating Tumor DNA of Patients With Advanced ALK-Positive NSCLC With Disease Progression During Crizotinib Treatment.	Crizotinib	138-148	ALK receptor tyrosine kinase	Homo sapiens	87-90
29048652-2	2017	Various ALK inhibitors are in clinical use for the treatment of ALK-NSCLC, including the first generation ALK inhibitor, crizotinib, and recently the more highly potent alectinib and ceritinib.	Crizotinib	121-131	anaplastic lymphoma kinase	Mus musculus	8-11
28601386-1	2017	BACKGROUND: In patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), disease progression occurs after a median of 9 to 10 months of crizotinib treatment.	Crizotinib	170-180	ALK receptor tyrosine kinase	Homo sapiens	29-55
28601386-1	2017	BACKGROUND: In patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), disease progression occurs after a median of 9 to 10 months of crizotinib treatment.	Crizotinib	170-180	ALK receptor tyrosine kinase	Homo sapiens	57-60
28601386-9	2017	CONCLUSION: ALK and KRAS mutations are associated with acquired resistance to crizotinib in ALK-positive NSCLC.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	12-15
28601386-9	2017	CONCLUSION: ALK and KRAS mutations are associated with acquired resistance to crizotinib in ALK-positive NSCLC.	Crizotinib	78-88	KRAS proto-oncogene, GTPase	Homo sapiens	20-24
28601386-9	2017	CONCLUSION: ALK and KRAS mutations are associated with acquired resistance to crizotinib in ALK-positive NSCLC.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	92-95
29268554-0	2017	Crizotinib plus radiotherapy in brain oligoprogressive NSCLC ROS1 rearranged and PD-L1 strong.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	61-65
29268554-3	2017	We describe a case of an 18 years old woman, never smoker, with NSCLC ROS1+ and miliary brain metastases treated with crizotinib and radiotherapy.	Crizotinib	118-128	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	70-74
29268554-9	2017	Our report indicates that the integration of crizotinib with local treatments should be considered in ROS1 NSCLC patients experiencing oligometastatic progression.	Crizotinib	45-55	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	102-106
28845578-0	2017	Patient harboring a novel PIK3CA point mutation after acquired resistance to crizotinib in an adenocarcinoma with ROS1 rearrangement: A case report and literature review.	Crizotinib	77-87	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	26-32
28845578-0	2017	Patient harboring a novel PIK3CA point mutation after acquired resistance to crizotinib in an adenocarcinoma with ROS1 rearrangement: A case report and literature review.	Crizotinib	77-87	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	114-118
28845578-3	2017	The mechanism of acquired resistance to crizotinib in patients with NSCLC with ROS1 rearrangement has not yet been identified.	Crizotinib	40-50	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	79-83
28845578-9	2017	This case is the second report of bypass activation conferred crizotinib resistance in a patient with NSCLC with ROS1-rearrangement, but is the first to confirm that activation of the mTOR signaling pathway leads to acquired crizotinib resistance.	Crizotinib	62-72	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	113-117
28845578-9	2017	This case is the second report of bypass activation conferred crizotinib resistance in a patient with NSCLC with ROS1-rearrangement, but is the first to confirm that activation of the mTOR signaling pathway leads to acquired crizotinib resistance.	Crizotinib	62-72	mechanistic target of rapamycin kinase	Homo sapiens	184-188
28845578-9	2017	This case is the second report of bypass activation conferred crizotinib resistance in a patient with NSCLC with ROS1-rearrangement, but is the first to confirm that activation of the mTOR signaling pathway leads to acquired crizotinib resistance.	Crizotinib	225-235	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	113-117
28845578-9	2017	This case is the second report of bypass activation conferred crizotinib resistance in a patient with NSCLC with ROS1-rearrangement, but is the first to confirm that activation of the mTOR signaling pathway leads to acquired crizotinib resistance.	Crizotinib	225-235	mechanistic target of rapamycin kinase	Homo sapiens	184-188
29066738-0	2017	ALK and IGF-1R as independent targets in crizotinib resistant lung cancer.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	0-3
29066738-0	2017	ALK and IGF-1R as independent targets in crizotinib resistant lung cancer.	Crizotinib	41-51	insulin like growth factor 1 receptor	Homo sapiens	8-14
29066738-1	2017	ALK positive non-small cell lung cancer is highly responsive to ALK inhibitors such as crizotinib, but drug resistance typically develops within a year of treatment.	Crizotinib	87-97	ALK receptor tyrosine kinase	Homo sapiens	0-3
29066738-1	2017	ALK positive non-small cell lung cancer is highly responsive to ALK inhibitors such as crizotinib, but drug resistance typically develops within a year of treatment.	Crizotinib	87-97	ALK receptor tyrosine kinase	Homo sapiens	64-67
29066738-3	2017	We confirmed that combination ALK and IGF-1R inhibitor treatment is synergistically cytotoxic to ALK-positive lung cancer cells and that this remains the case for at least 12 days after initial exposure to crizotinib.	Crizotinib	206-216	ALK receptor tyrosine kinase	Homo sapiens	30-33
29066738-3	2017	We confirmed that combination ALK and IGF-1R inhibitor treatment is synergistically cytotoxic to ALK-positive lung cancer cells and that this remains the case for at least 12 days after initial exposure to crizotinib.	Crizotinib	206-216	insulin like growth factor 1 receptor	Homo sapiens	38-44
29066738-4	2017	ALK-positive cells with acquired resistance to crizotinib did not acquire cross-resistance to IGF-1R inhibition, though combination treatment in the resistant cells gave additive rather than synergistic cytotoxicity.	Crizotinib	47-57	ALK receptor tyrosine kinase	Homo sapiens	0-3
28806116-13	2017	Patients with ROS1 gene rearrangement without prior crizotinib may be offered crizotinib, or if they previously received crizotinib, they may be offered chemotherapy.	Crizotinib	78-88	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	14-18
28806116-13	2017	Patients with ROS1 gene rearrangement without prior crizotinib may be offered crizotinib, or if they previously received crizotinib, they may be offered chemotherapy.	Crizotinib	78-88	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	14-18
29075144-2	2017	Crizotinib was the first approved ALK inhibitor with significant benefits over chemotherapy.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	34-37
29075144-4	2017	Several next-generation ALK inhibitors have been developed to overcome these resistance mechanisms and have demonstrated clinical benefits in crizotinib-refractory non-small cell lung cancer including in central nervous system.	Crizotinib	142-152	ALK receptor tyrosine kinase	Homo sapiens	24-27
29042798-3	2017	Crizotinib is a multi-targeted small-molecule kinase inhibitor for MET, ALK, and ROS1 kinases.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	72-75
28818606-2	2017	In a phase I study, the multitargeted MET proto-oncogene, receptor tyrosine kinase/anaplastic lymphoma kinase/ROS1 inhibitor crizotinib demonstrated remarkable efficacy in ROS1-rearranged NSCLCs and consequently gained approval by the United States Food and Drug Administration and by the European Medicines Agency in 2016.	Crizotinib	125-135	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	110-114
28818606-2	2017	In a phase I study, the multitargeted MET proto-oncogene, receptor tyrosine kinase/anaplastic lymphoma kinase/ROS1 inhibitor crizotinib demonstrated remarkable efficacy in ROS1-rearranged NSCLCs and consequently gained approval by the United States Food and Drug Administration and by the European Medicines Agency in 2016.	Crizotinib	125-135	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	172-176
28961830-0	2017	Combination therapy of erlotinib/crizotinib in a lung adenocarcinoma patient with primary EGFR mutation plus secondary MET amplification and a novel acquired crizotinib-resistant mutation MET G1108C.	Crizotinib	33-43	epidermal growth factor receptor	Homo sapiens	90-94
28419723-13	2017	Among patients who discontinued crizotinib, over half received no further antineoplastic therapy and OS was poor, particularly among patients without second-generation ALK inhibitor use.	Crizotinib	32-42	ALK receptor tyrosine kinase	Homo sapiens	168-171
28419723-14	2017	These findings suggest a need for greater access to effective treatments following crizotinib discontinuation for ALK+ NSCLC patients in Korea.	Crizotinib	83-93	ALK receptor tyrosine kinase	Homo sapiens	114-117
28705139-11	2017	CONCLUSIONS: Detection of ALK expression by IHC is reliable and the most practical way of identifying NSCLC patients likely to benefit from crizotinib treatment.	Crizotinib	140-150	ALK receptor tyrosine kinase	Homo sapiens	26-29
28245430-15	2017	HUH7, A-172, and PC3 cells that expressed MAN2A1-FER were about 2-fold more sensitive to the FER kinase inhibitor crizotinib and the epidermal growth factor receptor kinase inhibitor canertinib; these drugs slowed growth of xenograft tumors from MAN2A1-FER cells and prevented their metastasis in mice.	Crizotinib	114-124	MIR7-3 host gene	Homo sapiens	0-4
28245430-15	2017	HUH7, A-172, and PC3 cells that expressed MAN2A1-FER were about 2-fold more sensitive to the FER kinase inhibitor crizotinib and the epidermal growth factor receptor kinase inhibitor canertinib; these drugs slowed growth of xenograft tumors from MAN2A1-FER cells and prevented their metastasis in mice.	Crizotinib	114-124	chromobox 8	Homo sapiens	17-20
28245430-15	2017	HUH7, A-172, and PC3 cells that expressed MAN2A1-FER were about 2-fold more sensitive to the FER kinase inhibitor crizotinib and the epidermal growth factor receptor kinase inhibitor canertinib; these drugs slowed growth of xenograft tumors from MAN2A1-FER cells and prevented their metastasis in mice.	Crizotinib	114-124	mannosidase alpha class 2A member 1	Homo sapiens	42-48
28245430-15	2017	HUH7, A-172, and PC3 cells that expressed MAN2A1-FER were about 2-fold more sensitive to the FER kinase inhibitor crizotinib and the epidermal growth factor receptor kinase inhibitor canertinib; these drugs slowed growth of xenograft tumors from MAN2A1-FER cells and prevented their metastasis in mice.	Crizotinib	114-124	FER tyrosine kinase	Homo sapiens	49-52
28245430-15	2017	HUH7, A-172, and PC3 cells that expressed MAN2A1-FER were about 2-fold more sensitive to the FER kinase inhibitor crizotinib and the epidermal growth factor receptor kinase inhibitor canertinib; these drugs slowed growth of xenograft tumors from MAN2A1-FER cells and prevented their metastasis in mice.	Crizotinib	114-124	FER tyrosine kinase	Homo sapiens	93-96
28245430-15	2017	HUH7, A-172, and PC3 cells that expressed MAN2A1-FER were about 2-fold more sensitive to the FER kinase inhibitor crizotinib and the epidermal growth factor receptor kinase inhibitor canertinib; these drugs slowed growth of xenograft tumors from MAN2A1-FER cells and prevented their metastasis in mice.	Crizotinib	114-124	mannosidase alpha class 2A member 1	Homo sapiens	246-252
28245430-15	2017	HUH7, A-172, and PC3 cells that expressed MAN2A1-FER were about 2-fold more sensitive to the FER kinase inhibitor crizotinib and the epidermal growth factor receptor kinase inhibitor canertinib; these drugs slowed growth of xenograft tumors from MAN2A1-FER cells and prevented their metastasis in mice.	Crizotinib	114-124	FER tyrosine kinase	Homo sapiens	93-96
30082557-0	2017	Efficacy of crizotinib in ALK mutant non-small cell lung cancers that are positive by IHC but negative by FISH compared to FISH positive cases.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	26-29
30082557-5	2017	Depending upon feasibility, patients received either platinum based doublet chemotherapy or the ALK inhibitor crizotinib as first line therapy.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	96-99
30082557-9	2017	The difference in ORR of ALK IHC+/FISH- when compared to our historical cohort of ALK FISH positive treated with crizotinib was not statistically significant (57.15% vs 69.8%; P = 0.265).	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	82-85
30082557-11	2017	CONCLUSION: NSCLCs positive for ALK mutation by IHC but not detected by FISH show good response to crizotinib and merit treatment with the same.	Crizotinib	99-109	ALK receptor tyrosine kinase	Homo sapiens	32-35
28332225-0	2017	Molecular Dynamics Validation of Crizotinib Resistance to ALK Mutations (L1196M and G1269A) and Identification of Specific Inhibitors.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	58-61
28332225-2	2017	Crizotinib is the first generation ALK inhibitor practiced as a primary chemo to combat cancer cells followed by second generation inhibitor ceritinib which are effective against crizotinib resistant ALK mutations.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	35-38
28332225-2	2017	Crizotinib is the first generation ALK inhibitor practiced as a primary chemo to combat cancer cells followed by second generation inhibitor ceritinib which are effective against crizotinib resistant ALK mutations.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	200-203
28332225-4	2017	In this study we explored the crizotinib resistance in the presence of ALK mutations L1196M and G1269A through molecular dynamics simulation studies.	Crizotinib	30-40	ALK receptor tyrosine kinase	Homo sapiens	71-74
28332225-6	2017	This computational investigation in-sighted the molecular factors involved in crizotinib resistance which enhanced in the identification of new ALK drugs that brings individualized medicine to treat ALK positive NSCLC patients with specific mutations.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	144-147
28332225-6	2017	This computational investigation in-sighted the molecular factors involved in crizotinib resistance which enhanced in the identification of new ALK drugs that brings individualized medicine to treat ALK positive NSCLC patients with specific mutations.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	199-202
28075018-2	2017	Several approaches have been developed for targeting HGF and/or c-Met, and one of them, crizotinib (dual c-Met/ALK inhibitor), is recently been approved by FDA for lung-cancers with ALK-rearrangement.	Crizotinib	88-98	hepatocyte growth factor	Homo sapiens	53-56
28075018-2	2017	Several approaches have been developed for targeting HGF and/or c-Met, and one of them, crizotinib (dual c-Met/ALK inhibitor), is recently been approved by FDA for lung-cancers with ALK-rearrangement.	Crizotinib	88-98	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	64-69
28075018-2	2017	Several approaches have been developed for targeting HGF and/or c-Met, and one of them, crizotinib (dual c-Met/ALK inhibitor), is recently been approved by FDA for lung-cancers with ALK-rearrangement.	Crizotinib	88-98	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	105-110
28075018-2	2017	Several approaches have been developed for targeting HGF and/or c-Met, and one of them, crizotinib (dual c-Met/ALK inhibitor), is recently been approved by FDA for lung-cancers with ALK-rearrangement.	Crizotinib	88-98	ALK receptor tyrosine kinase	Homo sapiens	111-114
28075018-2	2017	Several approaches have been developed for targeting HGF and/or c-Met, and one of them, crizotinib (dual c-Met/ALK inhibitor), is recently been approved by FDA for lung-cancers with ALK-rearrangement.	Crizotinib	88-98	ALK receptor tyrosine kinase	Homo sapiens	182-185
28667686-1	2017	WHAT IS KNOWN AND OBJECTIVE: Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is a distinct subtype with patients showing peculiar clinicopathological features and dramatic responses to the ALK tyrosine kinase inhibitor crizotinib.	Crizotinib	250-260	ALK receptor tyrosine kinase	Homo sapiens	29-55
28667686-1	2017	WHAT IS KNOWN AND OBJECTIVE: Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is a distinct subtype with patients showing peculiar clinicopathological features and dramatic responses to the ALK tyrosine kinase inhibitor crizotinib.	Crizotinib	250-260	ALK receptor tyrosine kinase	Homo sapiens	57-60
28787259-0	2017	Targeting ALK With Crizotinib in Pediatric Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic Tumor: A Children"s Oncology Group Study.	Crizotinib	19-29	ALK receptor tyrosine kinase	Homo sapiens	10-13
28787259-2	2017	We assessed the activity of the ALK inhibitor crizotinib in patients who had no known curative treatment options at diagnosis or with relapsed/recurrent disease.	Crizotinib	46-56	ALK receptor tyrosine kinase	Homo sapiens	32-35
28787259-13	2017	Conclusion The robust and sustained clinical responses to crizotinib therapy in patients with relapsed ALCL and metastatic or unresectable IMT highlight the importance of the ALK pathway in these diseases.	Crizotinib	58-68	ALK receptor tyrosine kinase	Homo sapiens	175-178
28499860-0	2017	Circulating Tumor DNA Identifies EGFR Coamplification as a Mechanism of Resistance to Crizotinib in a Patient with Advanced MET-Amplified Lung Adenocarcinoma.	Crizotinib	86-96	epidermal growth factor receptor	Homo sapiens	33-37
29184678-2	2017	However, under crizotinib, a first-generation ALK-inhibitor, patients develop drug resistance after a median of 12 months.	Crizotinib	15-25	ALK receptor tyrosine kinase	Homo sapiens	46-49
29184678-3	2017	To overcome crizotinib resistance, several next-generation ALK inhibitors have been developed.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	59-62
29268402-10	2017	Thirty-three ALK and six ROS1 rearrangement patients received crizotinib treatment at an advanced stage.	Crizotinib	62-72	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	25-29
29109791-5	2017	The extracted tumor was subcutaneously injected into mice, which were then treated either with radiation, the specific ALK inhibitor crizotinib, or a combination of therapies.	Crizotinib	133-143	anaplastic lymphoma kinase	Mus musculus	119-122
29109791-6	2017	One of these combinations, namely, ALK-targeted GNP (via crizotinib coating), was found to enhance radiation treatment, as demonstrated by a significant decrease in tumor volume over 24 days.	Crizotinib	57-67	ALK receptor tyrosine kinase	Homo sapiens	35-38
29042798-3	2017	Crizotinib is a multi-targeted small-molecule kinase inhibitor for MET, ALK, and ROS1 kinases.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	81-85
28838404-1	2017	BACKGROUND: ALK and ROS1 gene rearrangements are distinct molecular subsets of non-small-cell lung cancer (NSCLC), and they are strong predictive biomarkers of response to ALK/ROS1 inhibitors, such as crizotinib.	Crizotinib	201-211	ALK receptor tyrosine kinase	Homo sapiens	12-15
28926892-0	2017	[Effect and mechanism of silibinin on the inhibition of ALK positive NSCLC cells by sensitizing crizotinib].	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	56-59
28926892-1	2017	Objective: To explore the synergistic effect of silibinin combined with crizotinib on anaplastic lymphoma kinase positive (ALK+ ) non-small cell lung cancer (NSCLC) cells and its mechanism.	Crizotinib	72-82	ALK receptor tyrosine kinase	Homo sapiens	123-126
28926892-18	2017	Conclusion: Silibinin enhances the inhibitory effect of crizotinib on ALK positive NSCLC cells, which may be associated with suppression of ALK activity and mesenchymal-epithelial transition.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	70-73
28926892-18	2017	Conclusion: Silibinin enhances the inhibitory effect of crizotinib on ALK positive NSCLC cells, which may be associated with suppression of ALK activity and mesenchymal-epithelial transition.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	140-143
28882182-0	2017	(S)-crizotinib induces apoptosis in human non-small cell lung cancer cells by activating ROS independent of MTH1.	Crizotinib	0-14	nudix hydrolase 1	Homo sapiens	108-112
28882182-3	2017	Crizotinib, a selective small-molecule inhibitor, has been widely used for the treatment of NSCLC patients with ALK gene rearrangements.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	112-115
28882182-4	2017	A recent study has also shown that (S)-enantiomer of crizotinib exhibits anticancer activity by targeting the protein mutT homologue (MTH1).	Crizotinib	53-63	nudix hydrolase 1	Homo sapiens	134-138
28882182-5	2017	Since this discovery, contradictory studies have cast a doubt on MTH1 as a therapeutic target of (S)-crizotinib.	Crizotinib	97-111	nudix hydrolase 1	Homo sapiens	65-69
28882182-12	2017	CONCLUSIONS: Our results reveal a novel antitumor mechanism of (S)-crizotinib in NSCLC which involves activation of ROS-dependent ER stress apoptotic pathway and is independent of MTH1 inhibition.	Crizotinib	63-77	nudix hydrolase 1	Homo sapiens	180-184
28886275-5	2017	We hypothesized a mechanistic link between BRCA2-deficiency and c-MET overexpression and synergistic interaction between drugs that treat BRCA-deficient tumors (mitomycin C (MMC) or PARP inhibitors) and c-MET inhibitors (crizotinib).	Crizotinib	221-231	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	64-69
28886275-5	2017	We hypothesized a mechanistic link between BRCA2-deficiency and c-MET overexpression and synergistic interaction between drugs that treat BRCA-deficient tumors (mitomycin C (MMC) or PARP inhibitors) and c-MET inhibitors (crizotinib).	Crizotinib	221-231	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	203-208
28646771-0	2017	Efficacy of alectinib in central nervous system metastases in crizotinib-resistant ALK-positive non-small-cell lung cancer: Comparison of RECIST 1.1 and RANO-HGG criteria.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	83-86
28646771-1	2017	BACKGROUND: Central nervous system (CNS) progression is common in patients with anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) receiving crizotinib.	Crizotinib	168-178	ALK receptor tyrosine kinase	Homo sapiens	117-120
28794366-1	2017	Crizotinib, which is effective in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer, is sometimes associated with the generation of complex renal cysts.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	48-74
28794366-1	2017	Crizotinib, which is effective in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer, is sometimes associated with the generation of complex renal cysts.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	76-79
28794366-2	2017	A 56-year-old man with ALK positive adenocarcinoma received crizotinib.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	23-26
28336299-0	2017	Inhibitory Effect of Crizotinib on Creatinine Uptake by Renal Secretory Transporter OCT2.	Crizotinib	21-31	POU class 2 homeobox 2	Homo sapiens	84-88
28336299-3	2017	In the present study, we evaluated in vitro inhibitory effect of crizotinib on OCT2 by directly measuring creatinine uptake by OCT2.	Crizotinib	65-75	POU class 2 homeobox 2	Homo sapiens	79-83
28336299-3	2017	In the present study, we evaluated in vitro inhibitory effect of crizotinib on OCT2 by directly measuring creatinine uptake by OCT2.	Crizotinib	65-75	POU class 2 homeobox 2	Homo sapiens	127-131
28336299-6	2017	These IC50 values of crizotinib on [3H]N-methyl-4-phenylpyridinium acetate uptake by OCT2 were 10-20 times higher than those of [14C]creatinine uptake.	Crizotinib	21-31	POU class 2 homeobox 2	Homo sapiens	85-89
28336299-7	2017	Furthermore, preincubation of crizotinib inhibited creatinine uptake by OCT2 in an apparently competitive manner.	Crizotinib	30-40	POU class 2 homeobox 2	Homo sapiens	72-76
28336299-8	2017	In conclusion, crizotinib at a clinically relevant concentration has the potential to inhibit creatinine transport by OCT2, suggesting an increase of serum creatinine levels in clinical use.	Crizotinib	15-25	POU class 2 homeobox 2	Homo sapiens	118-122
28832416-5	2017	Targeted therapies are aimed at the products of these mutated genes and include agents such as erlotinib and gefitinib (in EGFR-mutant NSCLC) or crizotinib (in ALK-positive NSCLC).	Crizotinib	145-155	ALK receptor tyrosine kinase	Homo sapiens	160-163
28838404-1	2017	BACKGROUND: ALK and ROS1 gene rearrangements are distinct molecular subsets of non-small-cell lung cancer (NSCLC), and they are strong predictive biomarkers of response to ALK/ROS1 inhibitors, such as crizotinib.	Crizotinib	201-211	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	20-24
28838404-1	2017	BACKGROUND: ALK and ROS1 gene rearrangements are distinct molecular subsets of non-small-cell lung cancer (NSCLC), and they are strong predictive biomarkers of response to ALK/ROS1 inhibitors, such as crizotinib.	Crizotinib	201-211	ALK receptor tyrosine kinase	Homo sapiens	172-175
28838404-1	2017	BACKGROUND: ALK and ROS1 gene rearrangements are distinct molecular subsets of non-small-cell lung cancer (NSCLC), and they are strong predictive biomarkers of response to ALK/ROS1 inhibitors, such as crizotinib.	Crizotinib	201-211	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	176-180
28869223-6	2017	All the 3 ROS1-positive patients were females in their forties and started on crizotinib.	Crizotinib	78-88	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	10-14
28342113-2	2017	Crizotinib has previously been assessed by NICE for patients with previously treated ALK-positive NSCLC (TA 296).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	85-88
28342113-19	2017	Crizotinib was therefore recommended as an option for untreated ALK-positive advanced NSCLC in adults.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	64-67
28860822-0	2017	Response to crizotinib in a lung adenocarcinoma patient harboring a novel SLC34A2-ROS1 fusion variant.	Crizotinib	12-22	solute carrier family 34 member 2	Homo sapiens	74-81
28860822-0	2017	Response to crizotinib in a lung adenocarcinoma patient harboring a novel SLC34A2-ROS1 fusion variant.	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	82-86
28860822-2	2017	Crizotinib, an anaplastic lymphoma kinase inhibitor, shows efficacy in the treatment of lung cancer cases with ROS1 translocation.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	111-115
28860822-3	2017	We report the response to crizotinib of a lung adenocarcinoma patient harboring a novel SLC34A2-ROS1 fusion variant, which was different from the two common SLC34A2-ROS1 fusion types reported in the literature.	Crizotinib	26-36	solute carrier family 34 member 2	Homo sapiens	88-95
28860822-3	2017	We report the response to crizotinib of a lung adenocarcinoma patient harboring a novel SLC34A2-ROS1 fusion variant, which was different from the two common SLC34A2-ROS1 fusion types reported in the literature.	Crizotinib	26-36	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	96-100
28860822-3	2017	We report the response to crizotinib of a lung adenocarcinoma patient harboring a novel SLC34A2-ROS1 fusion variant, which was different from the two common SLC34A2-ROS1 fusion types reported in the literature.	Crizotinib	26-36	solute carrier family 34 member 2	Homo sapiens	157-164
28860822-3	2017	We report the response to crizotinib of a lung adenocarcinoma patient harboring a novel SLC34A2-ROS1 fusion variant, which was different from the two common SLC34A2-ROS1 fusion types reported in the literature.	Crizotinib	26-36	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	165-169
29209525-0	2017	Final results of the large-scale multinational trial PROFILE 1005: efficacy and safety of crizotinib in previously treated patients with advanced/metastatic ALK-positive non-small-cell lung cancer.	Crizotinib	90-100	ALK receptor tyrosine kinase	Homo sapiens	157-160
29209525-1	2017	Purpose: Crizotinib is a potent, orally administered tyrosine kinase inhibitor approved for the treatment of anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC).	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	109-135
29209525-1	2017	Purpose: Crizotinib is a potent, orally administered tyrosine kinase inhibitor approved for the treatment of anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC).	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	137-140
29209525-13	2017	Conclusion: The efficacy, safety and PRO profiles of crizotinib in this cohort of 1066 patients with ALK-positive NSCLC are consistent with previous reports.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	101-104
28634201-8	2017	Although Yamato-SS cells were sensitive to crizotinib (ALK/MET-inhibitor) but not pazopanib (VEGFR/PDGFR-inhibitor) monotherapy in vitro, synergistic effects were observed upon drug combination.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	55-58
28806414-0	2017	Alpha-tocopherol attenuates the anti-tumor activity of crizotinib against cells transformed by NPM-ALK.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	99-102
28806414-2	2017	The ALK inhibitor, crizotinib specifically induced apoptosis in Ba/F3 cells expressing NPM-ALK by inhibiting the activation of NPM-ALK and its downstream molecule, signal transducer and activator of transcription factor 3 (STAT3).	Crizotinib	19-29	anaplastic lymphoma kinase	Mus musculus	4-7
28806414-2	2017	The ALK inhibitor, crizotinib specifically induced apoptosis in Ba/F3 cells expressing NPM-ALK by inhibiting the activation of NPM-ALK and its downstream molecule, signal transducer and activator of transcription factor 3 (STAT3).	Crizotinib	19-29	ALK receptor tyrosine kinase	Homo sapiens	91-94
28806414-2	2017	The ALK inhibitor, crizotinib specifically induced apoptosis in Ba/F3 cells expressing NPM-ALK by inhibiting the activation of NPM-ALK and its downstream molecule, signal transducer and activator of transcription factor 3 (STAT3).	Crizotinib	19-29	anaplastic lymphoma kinase	Mus musculus	91-94
28806414-2	2017	The ALK inhibitor, crizotinib specifically induced apoptosis in Ba/F3 cells expressing NPM-ALK by inhibiting the activation of NPM-ALK and its downstream molecule, signal transducer and activator of transcription factor 3 (STAT3).	Crizotinib	19-29	signal transducer and activator of transcription 3	Mus musculus	164-221
28806414-2	2017	The ALK inhibitor, crizotinib specifically induced apoptosis in Ba/F3 cells expressing NPM-ALK by inhibiting the activation of NPM-ALK and its downstream molecule, signal transducer and activator of transcription factor 3 (STAT3).	Crizotinib	19-29	signal transducer and activator of transcription 3	Mus musculus	223-228
28806414-5	2017	Crizotinib also directly inhibited the kinase activity of NPM-ALK; however, this inhibitory effect was not altered by the co-treatment with alpha-tocopherol.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	62-65
28806414-6	2017	Whereas the nuclear localization of NPM-ALK was disappeared by the treatment with crizotinib, the co-treatment with alpha-tocopherol swept the effect of crizotinib and caused the localization of NPM-ALK in nucleus.	Crizotinib	82-92	ALK receptor tyrosine kinase	Homo sapiens	40-43
28806414-7	2017	The administration of alpha-tocopherol attenuated the anti-tumor activity of crizotinib against NPM-ALK-provoked tumorigenesis in vivo.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	100-103
28806414-8	2017	Furthermore, the alpha-tocopherol-induced inhibition of crizotinib-caused apoptosis was also observed in NPM-ALK-positive cells derived from ALCL patients, namely, SUDHL-1 and Ki-JK.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	109-112
28183714-3	2017	We evaluated tumor response rate and survival after crizotinib treatment of patients with advanced NSCLC with ALK activation using both dichotomous immunohistochemical (IHC) staining and FISH.Experimental Design: Patients with stage IV NSCLC treated with crizotinib were selected.	Crizotinib	52-62	ALK receptor tyrosine kinase	Homo sapiens	110-113
28183714-7	2017	All ALK-IHC-positive patients responded to crizotinib except three with primary resistance.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	4-7
28475456-1	2017	Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	46-77
28475456-1	2017	Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	80-83
28475456-1	2017	Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	124-127
28475456-2	2017	We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refractory ALK-positive NSCLC.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	116-119
28622610-0	2017	F1174V mutation alters the ALK active conformation in response to Crizotinib in NSCLC: Insight from molecular simulations.	Crizotinib	66-76	ALK receptor tyrosine kinase	Homo sapiens	27-30
28622610-1	2017	Crizotinib is an efficient antineoplastic drug for treatment of non-small cell lung carcinoma (NSCLC), which is identified as an anaplastic lymphoma kinase (ALK) inhibitor.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	129-155
28622610-1	2017	Crizotinib is an efficient antineoplastic drug for treatment of non-small cell lung carcinoma (NSCLC), which is identified as an anaplastic lymphoma kinase (ALK) inhibitor.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	157-160
28622610-8	2017	This study provided a molecular mechanism for ALK Crizotinib resistance caused by F1174V mutation,which could facilitate designing more efficient drugs.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	46-49
28676215-0	2017	Identification of a novel T1151K ALK mutation in a patient with ALK-rearranged NSCLC with prior exposure to crizotinib and ceritinib.	Crizotinib	108-118	ALK receptor tyrosine kinase	Homo sapiens	33-36
28676215-0	2017	Identification of a novel T1151K ALK mutation in a patient with ALK-rearranged NSCLC with prior exposure to crizotinib and ceritinib.	Crizotinib	108-118	ALK receptor tyrosine kinase	Homo sapiens	64-67
28676215-6	2017	Here we report for the first time a novel ALK T1151K mutation in a patient with metastatic ALK-rearranged NSCLC who progressed on crizotinib and then ceritinib.	Crizotinib	130-140	ALK receptor tyrosine kinase	Homo sapiens	42-45
28676215-6	2017	Here we report for the first time a novel ALK T1151K mutation in a patient with metastatic ALK-rearranged NSCLC who progressed on crizotinib and then ceritinib.	Crizotinib	130-140	ALK receptor tyrosine kinase	Homo sapiens	91-94
28676219-2	2017	All previously reported ALK-positive CBM developed during crizotinib treatment and were often asymptomatic and indolent, even without CNS-directed therapy.	Crizotinib	58-68	ALK receptor tyrosine kinase	Homo sapiens	24-27
28781781-0	2017	Responses to crizotinib and chemotherapy in patients with lung adenocarcinoma harboring a concomitant EGFR mutation and ALK gene rearrangement: A case report and review of the literature.	Crizotinib	13-23	epidermal growth factor receptor	Homo sapiens	102-106
28781781-0	2017	Responses to crizotinib and chemotherapy in patients with lung adenocarcinoma harboring a concomitant EGFR mutation and ALK gene rearrangement: A case report and review of the literature.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	120-123
28781781-4	2017	In the present case report, the case is described of a 53-year-old woman with stage IV lung adenocarcinoma, harboring a concomitant EGFR mutation and ALK gene rearrangement, who was refractory to gefitinib administration but demonstrated a good response to crizotinib and pemetrexed chemotherapy.	Crizotinib	257-267	epidermal growth factor receptor	Homo sapiens	132-136
28781781-4	2017	In the present case report, the case is described of a 53-year-old woman with stage IV lung adenocarcinoma, harboring a concomitant EGFR mutation and ALK gene rearrangement, who was refractory to gefitinib administration but demonstrated a good response to crizotinib and pemetrexed chemotherapy.	Crizotinib	257-267	ALK receptor tyrosine kinase	Homo sapiens	150-153
28781805-0	2017	Successful oral desensitization with crizotinib after crizotinib-induced hepatitis in an anaplastic lymphoma kinase-rearranged non-small-cell lung cancer patient: A case report.	Crizotinib	37-47	ALK receptor tyrosine kinase	Homo sapiens	89-115
28781805-0	2017	Successful oral desensitization with crizotinib after crizotinib-induced hepatitis in an anaplastic lymphoma kinase-rearranged non-small-cell lung cancer patient: A case report.	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	89-115
28781805-1	2017	Crizotinib is one of the molecularly-targeted agents targeted against anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	70-96
28781805-1	2017	Crizotinib is one of the molecularly-targeted agents targeted against anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	98-101
28781805-2	2017	Although its effects appear to be promising, crizotinib may cause adverse effects in patients with ALK-rearranged NSCLC.	Crizotinib	45-55	ALK receptor tyrosine kinase	Homo sapiens	99-102
28781805-4	2017	We herein report the case of a 51-year-old woman diagnosed with relapsed ALK-rearranged NSCLC, who received crizotinib as second-line systemic chemotherapy.	Crizotinib	108-118	ALK receptor tyrosine kinase	Homo sapiens	73-76
28432815-3	2017	Validation of the immunoassays is presented using a panel of neuroblastoma cell lines and evidence of on-target ALK inhibition provided by treatment of a genetically engineered murine model of neuroblastoma with two clinical ALK inhibitors, crizotinib and ceritinib, highlighting the superior efficacy of ceritinib.	Crizotinib	241-251	anaplastic lymphoma kinase	Mus musculus	112-115
28666189-1	2017	BACKGROUND: Anaplastic lymphoma kinase (ALK) inhibitor crizotinib has proven to be effective in the treatment of ALK-mutated neuroblastoma, but crizotinib resistance was commonly observed in patients.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	12-38
28666189-1	2017	BACKGROUND: Anaplastic lymphoma kinase (ALK) inhibitor crizotinib has proven to be effective in the treatment of ALK-mutated neuroblastoma, but crizotinib resistance was commonly observed in patients.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	40-43
28666189-1	2017	BACKGROUND: Anaplastic lymphoma kinase (ALK) inhibitor crizotinib has proven to be effective in the treatment of ALK-mutated neuroblastoma, but crizotinib resistance was commonly observed in patients.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	113-116
28666189-1	2017	BACKGROUND: Anaplastic lymphoma kinase (ALK) inhibitor crizotinib has proven to be effective in the treatment of ALK-mutated neuroblastoma, but crizotinib resistance was commonly observed in patients.	Crizotinib	144-154	ALK receptor tyrosine kinase	Homo sapiens	12-38
28666189-1	2017	BACKGROUND: Anaplastic lymphoma kinase (ALK) inhibitor crizotinib has proven to be effective in the treatment of ALK-mutated neuroblastoma, but crizotinib resistance was commonly observed in patients.	Crizotinib	144-154	ALK receptor tyrosine kinase	Homo sapiens	40-43
28666189-2	2017	We aimed to overcome crizotinib resistance by combining with the MEK inhibitor trametinib or low-dose metronomic (LDM) topotecan in preclinical neuroblastoma models.	Crizotinib	21-31	mitogen-activated protein kinase kinase 7	Homo sapiens	65-68
28666189-6	2017	RESULTS: All NBL cell lines responded to crizotinib treatment but at variable ED50 levels, ranging from 0.25 to 5.58 muM.	Crizotinib	41-51	latexin	Homo sapiens	117-120
28979145-2	2017	The clinically approved first-line treatment crizotinib specifically inhibits ALK and improves progression-free survival (PFS) in treated and untreated patients by 4 months compared to standard chemotherapy.	Crizotinib	45-55	ALK receptor tyrosine kinase	Homo sapiens	78-81
28979145-3	2017	While some patients relapse after crizotinib treatment due to resistance mutations in ALK, second-generation ALK inhibitors effectively induce tumor response and prolong PFS.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	86-89
28978110-5	2017	PD-L1 mRNA (qPCR) and protein (flow cytometry) expression was investigated after treatment with MET and mitogen-activated protein kinase (MAPK) targeting drugs (crizotinib and SCH772984, respectively).	Crizotinib	161-171	CD274 molecule	Homo sapiens	0-5
28346673-0	2017	Clinical features of Bim deletion polymorphism and its relation with crizotinib primary resistance in Chinese patients with ALK/ROS1 fusion-positive non-small cell lung cancer.	Crizotinib	69-79	ALK receptor tyrosine kinase	Homo sapiens	124-127
28346673-0	2017	Clinical features of Bim deletion polymorphism and its relation with crizotinib primary resistance in Chinese patients with ALK/ROS1 fusion-positive non-small cell lung cancer.	Crizotinib	69-79	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	128-132
28346673-3	2017	METHODS: A total of 55 patients with ALK-positive NSCLC and 14 patients with ROS1-positive NSCLC who were treated with crizotinib were enrolled into the current study.	Crizotinib	119-129	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	77-81
28346673-10	2017	Multivariate analysis indicated that the Bim deletion polymorphism was an independent predictive factor for patients with ALK-positive NSCLC who were treated with crizotinib (hazard ratio, 4.786 [P =.006]).	Crizotinib	163-173	ALK receptor tyrosine kinase	Homo sapiens	122-125
28346673-11	2017	CONCLUSIONS: The Bim deletion polymorphism was found to be associated with poor clinical response to crizotinib in patients with ALK fusion-positive NSCLC.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	129-132
28806414-9	2017	Collectively, these results not only revealed the novel mechanism underlying crizotinib-induced apoptosis in NPM-ALK-positive cells, but also suggest that the anti-tumor effects of crizotinib are attenuated when it is taken in combination with vitamin E.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	113-116
28806414-9	2017	Collectively, these results not only revealed the novel mechanism underlying crizotinib-induced apoptosis in NPM-ALK-positive cells, but also suggest that the anti-tumor effects of crizotinib are attenuated when it is taken in combination with vitamin E.	Crizotinib	181-191	ALK receptor tyrosine kinase	Homo sapiens	113-116
28514730-10	2017	Increased plasma levels of miR-660-5p after crizotinib treatment predicted good tumor response (p = 0.012).	Crizotinib	44-54	microRNA 660	Homo sapiens	27-34
28514730-13	2017	We also identified miR-660-5p and miR-362-5p as potential predictors for response to crizotinib treatment.	Crizotinib	85-95	microRNA 660	Homo sapiens	19-26
28465216-12	2017	Crizotinib was the first inhibitor approved by the US Food and Drug Administration for the treatment of ROS1-positive non-small cell lung cancer in 2016.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	104-108
28696381-6	2017	The current state-of-the-art ALK diagnostic procedure comprises a Fluorescent in situ Hybridization (FISH) assay accompanied by ALK inhibitor therapy (Crizotinib).	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	29-32
28696381-10	2017	We hypothesize that the wide variety of known (and unknown) ALK mutations is associated with a variable therapy success, thus rendering current companion diagnostic procedures (FISH) and therapy (Crizotinib) only partly applicable in ALK-related NSCLC treatment.	Crizotinib	196-206	ALK receptor tyrosine kinase	Homo sapiens	60-63
28740365-2	2017	Crizotinib was the first ALK tyrosine kinase inhibitor to receive fast approval and is currently indicated as the first-line therapy for advanced, ALK-positive NSCLC patients.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	25-28
28740365-2	2017	Crizotinib was the first ALK tyrosine kinase inhibitor to receive fast approval and is currently indicated as the first-line therapy for advanced, ALK-positive NSCLC patients.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	147-150
29086093-7	2017	Crizotinib co-targets ALK and MET.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	22-25
28578501-0	2017	Monitoring for and Characterizing Crizotinib Progression: A Chart Review of ALK-Positive Non-Small Cell Lung Cancer Patients.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	76-79
28578501-1	2017	INTRODUCTION: Crizotinib is recommended as first-line therapy for ALK-positive non-small cell lung cancer (NSCLC), but within a year of treatment initiation many patients develop resistance.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	66-69
28578501-14	2017	CONCLUSION: The findings from this physician survey and retrospective chart review study suggest that physician response to the development of new lesions in crizotinib-treated ALK-positive NSCLC patients varies with location and extent of the lesions.	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	177-180
28407036-0	2017	The clinical impact of an EML4-ALK variant on survival following crizotinib treatment in patients with advanced ALK-rearranged non-small-cell lung cancer.	Crizotinib	65-75	EMAP like 4	Homo sapiens	26-30
28407036-0	2017	The clinical impact of an EML4-ALK variant on survival following crizotinib treatment in patients with advanced ALK-rearranged non-small-cell lung cancer.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	31-34
28407036-0	2017	The clinical impact of an EML4-ALK variant on survival following crizotinib treatment in patients with advanced ALK-rearranged non-small-cell lung cancer.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	112-115
28474864-7	2017	A cell-based in vitro assay revealed that HGF/MET inhibition, induced either by MET inhibitors (crizotinib and golvatinib), or by siRNA-mediated knockdown of HGF or MET, constrained growth of chemoresistant SCLC cells through the inhibition of ERK and AKT signals.	Crizotinib	96-106	hepatocyte growth factor	Homo sapiens	42-45
28536155-1	2017	The FDA has approved the ALK inhibitor brigatinib for patients with metastatic non-small cell lung cancer who cannot take crizotinib or whose disease worsened despite its use.	Crizotinib	122-132	ALK receptor tyrosine kinase	Homo sapiens	25-28
27545320-1	2017	Alectinib, an anaplastic lymphoma kinase (ALK) inhibitor, is approved for treatment of patients with ALK+ non-small cell lung cancer who have progressed, on or are intolerant to, crizotinib.	Crizotinib	179-189	ALK receptor tyrosine kinase	Homo sapiens	42-45
28597393-3	2017	The development of resistance to crizotinib is a therapeutic challenge that has led to the development of second-generation ALK-inhibitors such as brigatinib, which have activity against treatment-resistant ALK mutants.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	124-127
28597393-3	2017	The development of resistance to crizotinib is a therapeutic challenge that has led to the development of second-generation ALK-inhibitors such as brigatinib, which have activity against treatment-resistant ALK mutants.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	207-210
28966724-7	2017	Furthermore, treatment with c-Met inhibitors (Crizotinib, Foretinib, PHA-665752 and Tivantinib) in MDA-MB157 cells with high c-Met protein expression resulted in significant suppression in cell viability, contrary to MDA-MB468 cells with low c-Met protein expression.	Crizotinib	46-56	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	28-33
28966724-7	2017	Furthermore, treatment with c-Met inhibitors (Crizotinib, Foretinib, PHA-665752 and Tivantinib) in MDA-MB157 cells with high c-Met protein expression resulted in significant suppression in cell viability, contrary to MDA-MB468 cells with low c-Met protein expression.	Crizotinib	46-56	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	125-130
28966724-7	2017	Furthermore, treatment with c-Met inhibitors (Crizotinib, Foretinib, PHA-665752 and Tivantinib) in MDA-MB157 cells with high c-Met protein expression resulted in significant suppression in cell viability, contrary to MDA-MB468 cells with low c-Met protein expression.	Crizotinib	46-56	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	125-130
28498406-6	2017	Crizotinib also inhibited RhoA activation in addition to MET phosphorylation.	Crizotinib	0-10	ras homolog family member A	Homo sapiens	26-30
28498406-9	2017	Taken together, crizotinib may be a potent drug for treating peritoneal dissemination of pancreatic cancer by inhibiting cancer cell proliferation and invasion, at least in part through the suppression of HGF/MET signaling and RhoA activation.	Crizotinib	16-26	hepatocyte growth factor	Homo sapiens	205-208
28498406-9	2017	Taken together, crizotinib may be a potent drug for treating peritoneal dissemination of pancreatic cancer by inhibiting cancer cell proliferation and invasion, at least in part through the suppression of HGF/MET signaling and RhoA activation.	Crizotinib	16-26	ras homolog family member A	Homo sapiens	227-231
28332433-1	2017	Introduction Anaplastic lymphoma kinase (ALK) targeting drugs provide an important option for advanced non-small cell lung cancer patients with this distinct tumor type; however, there is considerable uncertainty as to which drug provides the optimal value after crizotinib treatment.	Crizotinib	263-273	ALK receptor tyrosine kinase	Homo sapiens	41-44
28332433-11	2017	The ICER ranged from $10,600-$65,000 per QALY in scenario analyses, including a sub-group analysis limited to patients with prior chemotherapy and crizotinib treatment.	Crizotinib	147-157	cAMP responsive element modulator	Homo sapiens	4-8
28369553-2	2017	Data are presented from the phase II trial (ASCEND-2) evaluating efficacy and safety in a subset of Japanese patients with ALK-rearranged non-small cell lung cancer previously treated with platinum-based chemotherapy, who experienced disease progression on crizotinib.	Crizotinib	257-267	ALK receptor tyrosine kinase	Homo sapiens	123-126
28465216-14	2017	Crizotinib forms a complex within the front cleft between the small and large lobes of an active ROS1 protein-kinase domain and it is classified as type I inhibitor.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	97-101
28721071-2	2017	As an anaplastic lymphoma kinase (ALK) gene translocation was identified, the therapy was changed to crizotinib.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	6-32
28721071-2	2017	As an anaplastic lymphoma kinase (ALK) gene translocation was identified, the therapy was changed to crizotinib.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	34-37
28721068-0	2017	Patients harboring ALK rearrangement adenocarcinoma after acquired resistance to crizotinib and transformation to small-cell lung cancer: a case report.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	19-22
28721068-5	2017	Herein, we report a 49-year-old man diagnosed with adenocarcinoma, who was negative for EGFR and ALK genes as detected by reverse transcription polymerase chain reaction, and was treated with crizotinib.	Crizotinib	192-202	epidermal growth factor receptor	Homo sapiens	88-92
28721068-5	2017	Herein, we report a 49-year-old man diagnosed with adenocarcinoma, who was negative for EGFR and ALK genes as detected by reverse transcription polymerase chain reaction, and was treated with crizotinib.	Crizotinib	192-202	ALK receptor tyrosine kinase	Homo sapiens	97-100
28638122-6	2017	Combinations of HER-family inhibitors with NVP-AEW541, dasatinib or crizotinib (inhibitors of IGF-1R, Src and c-Met/ALK, respectively) led to synergistic effects in some of the cell lines examined.	Crizotinib	68-78	insulin like growth factor 1 receptor	Homo sapiens	94-100
28638122-6	2017	Combinations of HER-family inhibitors with NVP-AEW541, dasatinib or crizotinib (inhibitors of IGF-1R, Src and c-Met/ALK, respectively) led to synergistic effects in some of the cell lines examined.	Crizotinib	68-78	SRC proto-oncogene, non-receptor tyrosine kinase	Homo sapiens	102-105
28638122-6	2017	Combinations of HER-family inhibitors with NVP-AEW541, dasatinib or crizotinib (inhibitors of IGF-1R, Src and c-Met/ALK, respectively) led to synergistic effects in some of the cell lines examined.	Crizotinib	68-78	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	110-115
28638122-6	2017	Combinations of HER-family inhibitors with NVP-AEW541, dasatinib or crizotinib (inhibitors of IGF-1R, Src and c-Met/ALK, respectively) led to synergistic effects in some of the cell lines examined.	Crizotinib	68-78	ALK receptor tyrosine kinase	Homo sapiens	116-119
28427213-0	2017	Clinical benefit of continuing crizotinib therapy after initial disease progression in Chinese patients with advanced ALK-rearranged non-small-cell lung cancer.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	118-121
28427213-3	2017	MATERIALS AND METHODS: Data on 33 patients with ALK-positive NSCLC who achieved disease control with crizotinib were analyzed retrospectively.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	48-51
28427213-4	2017	The impact of continued crizotinib therapy on the patients" PFS2 time was assessed after adjusting for potential confounding factors.	Crizotinib	24-34	GINS complex subunit 2	Homo sapiens	60-64
28427213-6	2017	With continued crizotinib therapy after documentation of PD, the median PFS2 for all 33 patients was 16 weeks, and in those with CNS progression but systemic disease control it was 30 weeks.	Crizotinib	15-25	GINS complex subunit 2	Homo sapiens	72-76
28427213-8	2017	Multivariable Cox regression analysis showed that the PFS1 with initial crizotinib treatment and local therapy were independent predictors of PFS2.	Crizotinib	72-82	GINS complex subunit 2	Homo sapiens	142-146
28427213-9	2017	DISCUSSION: This study provides further evidence of the benefit of continuing crizotinib therapy in Chinese patients with progressive ALK-positive NSCLC.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	134-137
29088872-0	2017	Meta-analysis of incidence and risk of severe adverse events and fatal adverse events with crizotinib monotherapy in patients with ALK-positive NSCLC.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	131-134
29088872-1	2017	BACKGROUND: Numerous clinical trials show crizotinib has promising efficacy for anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients which trigger the substitution of traditional chemotherapy to be the current standard first-line treatment for these patients.	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	80-106
29088872-1	2017	BACKGROUND: Numerous clinical trials show crizotinib has promising efficacy for anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients which trigger the substitution of traditional chemotherapy to be the current standard first-line treatment for these patients.	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	108-111
28501140-16	2017	INTERPRETATION: These results provide the first head-to-head comparison of alectinib and crizotinib and have the potential to change the standard of care for the first-line treatment of ALK-positive non-small-cell lung cancer.	Crizotinib	89-99	ALK receptor tyrosine kinase	Homo sapiens	186-189
28881678-4	2017	The clinically available inhibitor of autophagy, chloroquine, or RNAi-mediated knockdown of two obligate components of the autophagy pathway (ATG5 and ATG7) blocked cell death induced by crizotinib or RNAi-mediated knockdown of MET, and mechanistic studies localized the effects of autophagy to cytochrome c release from the mitochondria.	Crizotinib	187-197	autophagy related 5	Homo sapiens	142-146
28881678-4	2017	The clinically available inhibitor of autophagy, chloroquine, or RNAi-mediated knockdown of two obligate components of the autophagy pathway (ATG5 and ATG7) blocked cell death induced by crizotinib or RNAi-mediated knockdown of MET, and mechanistic studies localized the effects of autophagy to cytochrome c release from the mitochondria.	Crizotinib	187-197	autophagy related 7	Homo sapiens	151-155
28881678-4	2017	The clinically available inhibitor of autophagy, chloroquine, or RNAi-mediated knockdown of two obligate components of the autophagy pathway (ATG5 and ATG7) blocked cell death induced by crizotinib or RNAi-mediated knockdown of MET, and mechanistic studies localized the effects of autophagy to cytochrome c release from the mitochondria.	Crizotinib	187-197	cytochrome c, somatic	Homo sapiens	295-307
28054318-2	2017	Crizotinib is an ALK inhibitor, which was approved in 2011 for the treatment of ALK-positive lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	17-20
28534251-2	2017	Crizotinib was the first agent approved for the management of ALK+ NSCLC patients after it demonstrated significantly greater clinical benefit compared to chemotherapy.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	62-65
28534251-3	2017	Several next generation ALK inhibitors have demonstrated clinical benefit in patients with crizotinib refractory NSCLC patients including in the CNS.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	24-27
28534251-4	2017	Based on available data, therapy with a next generation ALK inhibitor can be initiated following therapy with crizotinib without any assessment of the molecular mechanisms of resistance.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	56-59
28463570-1	2017	INTRODUCTION: Crizotinib is a first-in-class ALK tyrosine kinase inhibitor (TKI), which has proven its superiority over standard platinum-based chemotherapy for the first-line therapy of ALK-rearranged non-small cell lung cancer (NSCLC) patients.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	45-48
28463570-1	2017	INTRODUCTION: Crizotinib is a first-in-class ALK tyrosine kinase inhibitor (TKI), which has proven its superiority over standard platinum-based chemotherapy for the first-line therapy of ALK-rearranged non-small cell lung cancer (NSCLC) patients.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	187-190
28463570-4	2017	Several novel ALK inhibitors, more potent and with different selectivity compared to crizotinib, are currently in development.	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	14-17
28463570-9	2017	The molecular profile of the tumor at the time of disease progression to crizotinib is crucial for the sequencing of novel ALK TKIs.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	123-126
28599410-8	2017	Cabozantinib and crizotinib sensitized tumor cells to nab-paclitaxel and paclitaxel in the same dose-dependent manner in cell lines overexpressing ABCB1, without altering the downstream signaling of tyrosine kinases.	Crizotinib	17-27	ATP binding cassette subfamily B member 1	Homo sapiens	147-152
28513466-8	2017	Currently, for NSCLC treatment a number of EGFR inhibitors such as erlotinib, gefitinib, afatinib and two compounds targeted in ALK kinase crizotinib and ceritinib are applied.	Crizotinib	139-149	ALK receptor tyrosine kinase	Homo sapiens	128-131
28427172-3	2017	Next, we measured the effect of crizotinib on the cartilage degeneration induced by interleukin-1beta in chondrocytes.	Crizotinib	32-42	interleukin 1 beta	Mus musculus	84-101
28427172-4	2017	Crizotinib ameliorated the pathological changes induced by interleukin-1beta via its anti-angiogenesis function.	Crizotinib	0-10	interleukin 1 beta	Mus musculus	59-76
28405961-11	2017	CONCLUSION: These early findings of ceritinib use in clinical practice suggest that ceritinib is effective at treating crizotinib-experienced ALK-positive NSCLC patients, regardless of metastatic sites or initial dose, and dosing ceritinib with food may lead to fewer gastrointestinal AEs.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	142-145
28717217-2	2017	The ROS1 tyrosine kinase inhibitor (TKI) crizotinib has induced marked tumour shrinkage in ROS1-rearranged cancers.	Crizotinib	41-51	Ros1 proto-oncogene	Mus musculus	4-8
28717217-4	2017	Previous findings indicate that cabozantinib overcomes secondary mutation-mediated crizotinib-resistance in ROS1-fusion-positive cells.	Crizotinib	83-93	Ros1 proto-oncogene	Mus musculus	108-112
27443585-10	2017	Treatment is primarily surgical, but targeted therapies (crizotinib) might be a solution for ALK1 rearranged cases with a poor prognosis.	Crizotinib	57-67	activin A receptor like type 1	Homo sapiens	93-97
28369651-9	2017	In vitro transport studies revealed that crizotinib is a potent inhibitor of the transport activities of BCRP (IC50: 5.7 microM, 95% CI: 2.7-11.8 microM) and P-gp (IC50: 7.8 microM, 95% CI: 3.4-18.0 microM).	Crizotinib	41-51	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	105-109
28369651-9	2017	In vitro transport studies revealed that crizotinib is a potent inhibitor of the transport activities of BCRP (IC50: 5.7 microM, 95% CI: 2.7-11.8 microM) and P-gp (IC50: 7.8 microM, 95% CI: 3.4-18.0 microM).	Crizotinib	41-51	ATP binding cassette subfamily B member 1	Homo sapiens	158-162
28369651-11	2017	IC50 values for transporter inhibition and trophoblast cell viability were similar to the tissue concentrations reached, suggesting that crizotinib can inhibit placental BCRP and P-gp function and possibly affect trophoblast viability.	Crizotinib	137-147	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	170-174
28369651-11	2017	IC50 values for transporter inhibition and trophoblast cell viability were similar to the tissue concentrations reached, suggesting that crizotinib can inhibit placental BCRP and P-gp function and possibly affect trophoblast viability.	Crizotinib	137-147	ATP binding cassette subfamily B member 1	Homo sapiens	179-183
28868009-0	2017	Good Tolerance to Full-Dose Crizotinib in a Patient with Anaplastic Lymphoma Receptor Tyrosine Kinase-Rearranged Lung Adenocarcinoma and Preexisting Renal Impairment.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	57-101
28868009-1	2017	BACKGROUND: Crizotinib is an approved tyrosine kinase inhibitor in the treatment of advanced-stage non-small-cell lung cancer patients with anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangement.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	140-184
28868009-1	2017	BACKGROUND: Crizotinib is an approved tyrosine kinase inhibitor in the treatment of advanced-stage non-small-cell lung cancer patients with anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangement.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	186-189
28868009-5	2017	We therefore proposed a treatment with full-dose crizotinib despite the renal impairment (creatinine clearance: 33 mL/min/1.73 m2) of unknown origin.	Crizotinib	49-59	CD59 molecule (CD59 blood group)	Homo sapiens	118-123
29088872-3	2017	Hence, we performed a first meta-analysis to determine the risk of crizotinib-related severe adverse events (SAEs) and fatal adverse events (FAEs) in ALK positive NSCLC patients.	Crizotinib	67-77	ALK receptor tyrosine kinase	Homo sapiens	150-153
29088872-4	2017	MATERIALS AND METHODS: A systematic literature search was conducted through December 2016 to identify clinical trials that reported crizotinib monotherapy in ALK-positive NSCLC patients.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	158-161
28461563-0	2017	Circulating Tumor Cells with Aberrant ALK Copy Number Predict Progression-Free Survival during Crizotinib Treatment in ALK-Rearranged Non-Small Cell Lung Cancer Patients.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	38-41
28938595-7	2017	Concomitant activation of MET did not contribute to resistance as crizotinib completely suppressed both p-MET and p-ALK in H3122/CR-1 cells, whose survival was not affected by crizotinib.	Crizotinib	66-76	ALK receptor tyrosine kinase	Homo sapiens	116-119
28938595-7	2017	Concomitant activation of MET did not contribute to resistance as crizotinib completely suppressed both p-MET and p-ALK in H3122/CR-1 cells, whose survival was not affected by crizotinib.	Crizotinib	66-76	complement C3b/C4b receptor 1 (Knops blood group)	Homo sapiens	129-133
28461563-0	2017	Circulating Tumor Cells with Aberrant ALK Copy Number Predict Progression-Free Survival during Crizotinib Treatment in ALK-Rearranged Non-Small Cell Lung Cancer Patients.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	119-122
28461563-1	2017	The duration and magnitude of clinical response are unpredictable in ALK-rearranged non-small cell lung cancer (NSCLC) patients treated with crizotinib, although all patients invariably develop resistance.	Crizotinib	141-151	ALK receptor tyrosine kinase	Homo sapiens	69-72
28277868-2	2017	This study aimed to estimate the budget impact of crizotinib versus other standard therapies in Thai advanced NSCLC patients with ALK rearrangement.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	130-133
28461563-3	2017	Thirty-nine ALK-rearranged NSCLC patients treated with crizotinib as first ALK inhibitor were recruited prospectively.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	12-15
28461563-3	2017	Thirty-nine ALK-rearranged NSCLC patients treated with crizotinib as first ALK inhibitor were recruited prospectively.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	75-78
28461563-8	2017	However, we observed a significant association between the decrease in CTC number with ALK-CNG on crizotinib and a longer PFS (likelihood ratio test, P = 0.025).	Crizotinib	98-108	ALK receptor tyrosine kinase	Homo sapiens	87-90
28461563-10	2017	Although not dominant, ALK-CNG has been reported to be one of the mechanisms of acquired resistance to crizotinib in tumor biopsies.	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	23-26
28461563-11	2017	Our results suggest that the dynamic change in the numbers of CTCs with ALK-CNG may be a predictive biomarker for crizotinib efficacy in ALK-rearranged NSCLC patients.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	72-75
28461563-11	2017	Our results suggest that the dynamic change in the numbers of CTCs with ALK-CNG may be a predictive biomarker for crizotinib efficacy in ALK-rearranged NSCLC patients.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	137-140
28730760-6	2017	Even in patients with crizotinib-resistant disease, second generation ALK inhibitors display prominent clinical activity.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	70-73
27922734-1	2017	Ceritinib is a second-generation selective and potent oral anaplastic lymphoma kinase (ALK) inhibitor approved for ALK-positive advanced non-small cell lung cancer previously treated with crizotinib.	Crizotinib	188-198	ALK receptor tyrosine kinase	Homo sapiens	87-90
28147239-0	2017	A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible for Treatment with Crizotinib.	Crizotinib	111-121	ALK receptor tyrosine kinase	Homo sapiens	12-15
28147239-1	2017	INTRODUCTION: The availability of high-quality, rigorously validated diagnostic tests that can be broadly implemented is necessary to efficiently identify patients with anaplastic lymphoma kinase (ALK)-positive NSCLC who can potentially benefit from treatment with crizotinib.	Crizotinib	265-275	ALK receptor tyrosine kinase	Homo sapiens	169-195
28147239-1	2017	INTRODUCTION: The availability of high-quality, rigorously validated diagnostic tests that can be broadly implemented is necessary to efficiently identify patients with anaplastic lymphoma kinase (ALK)-positive NSCLC who can potentially benefit from treatment with crizotinib.	Crizotinib	265-275	ALK receptor tyrosine kinase	Homo sapiens	197-200
28147239-11	2017	CONCLUSIONS: The ALK (D5F3) CDx assay is a stand-alone companion diagnostic test for identification of patients for treatment with crizotinib.	Crizotinib	131-141	ALK receptor tyrosine kinase	Homo sapiens	17-20
28538401-0	2017	Atrial fibrillation was changed into sinus bradycardia in a ROS1-positive advanced lung adenocarcinoma patient who achieved durable response to Crizotinib: A case report and literature review.	Crizotinib	144-154	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	60-64
28538401-10	2017	LESSONS: The present study demonstrates dramatic benefit of crizotinib for patients with ROS1 rearrangement.	Crizotinib	60-70	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	89-93
30225407-0	2017	A Rare STRN-ALK Fusion in Lung Adenocarcinoma Identified Using Next-Generation Sequencing-Based Circulating Tumor DNA Profiling Exhibits Excellent Response to Crizotinib.	Crizotinib	159-169	striatin	Homo sapiens	7-11
30225407-0	2017	A Rare STRN-ALK Fusion in Lung Adenocarcinoma Identified Using Next-Generation Sequencing-Based Circulating Tumor DNA Profiling Exhibits Excellent Response to Crizotinib.	Crizotinib	159-169	ALK receptor tyrosine kinase	Homo sapiens	12-15
30225407-2	2017	It includes the EML4-ALK rearrangement as a recurring event that renders the tumor sensitive to ALK tyrosine kinase inhibitor crizotinib.	Crizotinib	126-136	EMAP like 4	Homo sapiens	16-20
30225407-2	2017	It includes the EML4-ALK rearrangement as a recurring event that renders the tumor sensitive to ALK tyrosine kinase inhibitor crizotinib.	Crizotinib	126-136	ALK receptor tyrosine kinase	Homo sapiens	21-24
30225407-2	2017	It includes the EML4-ALK rearrangement as a recurring event that renders the tumor sensitive to ALK tyrosine kinase inhibitor crizotinib.	Crizotinib	126-136	ALK receptor tyrosine kinase	Homo sapiens	96-99
30225407-13	2017	This is the first clinical evidence involving advanced NSCLC due to a rare STRN-ALK fusion and has been effectively treated with crizotinib.	Crizotinib	129-139	striatin	Homo sapiens	75-79
30225407-13	2017	This is the first clinical evidence involving advanced NSCLC due to a rare STRN-ALK fusion and has been effectively treated with crizotinib.	Crizotinib	129-139	ALK receptor tyrosine kinase	Homo sapiens	80-83
28318251-2	2017	Since they have 49% amide acid sequence homology in the kinases domain and 77% identity at the ATP binding area, some ALK inhibitors also showed some significant responses for ROS1 in the clinical trial, such as the type-I binding inhibitor crizotinib and PF-06463922.	Crizotinib	241-251	ALK receptor tyrosine kinase	Homo sapiens	118-121
28318251-2	2017	Since they have 49% amide acid sequence homology in the kinases domain and 77% identity at the ATP binding area, some ALK inhibitors also showed some significant responses for ROS1 in the clinical trial, such as the type-I binding inhibitor crizotinib and PF-06463922.	Crizotinib	241-251	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	176-180
28469773-1	2017	Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	42-68
28469773-1	2017	Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	70-73
28469773-1	2017	Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	76-92
28469773-1	2017	Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	94-98
28469773-1	2017	Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	104-109
28469773-1	2017	Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	130-163
28469773-1	2017	Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	331-334
28469773-1	2017	Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	338-342
28469773-3	2017	In this study, our data show that crizotinib can actively induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreasing phosphorylation of the downstream signaling effectors AKT and ERK in human ovarian cancer cells.	Crizotinib	34-44	AKT serine/threonine kinase 1	Homo sapiens	209-212
28469773-3	2017	In this study, our data show that crizotinib can actively induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreasing phosphorylation of the downstream signaling effectors AKT and ERK in human ovarian cancer cells.	Crizotinib	34-44	mitogen-activated protein kinase 1	Homo sapiens	217-220
28404650-0	2017	Identification of a novel crizotinib-sensitive BCL11A-ALK gene fusion in a nonsmall cell lung cancer patient.	Crizotinib	26-36	BAF chromatin remodeling complex subunit BCL11A	Homo sapiens	47-53
28404650-0	2017	Identification of a novel crizotinib-sensitive BCL11A-ALK gene fusion in a nonsmall cell lung cancer patient.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	54-57
28435288-5	2017	In patients with ALK-rearranged lung cancers who receive brigatinib after crizotinib, substantial and durable responses and intracranial disease control can be achieved based on early-phase clinical trial data.	Crizotinib	74-84	ALK receptor tyrosine kinase	Homo sapiens	17-20
28320945-5	2017	Addition of the dual MET/RON tyrosine kinase inhibitor, crizotinib, restored cetuximab sensitivity in SC.	Crizotinib	56-66	macrophage stimulating 1 receptor	Homo sapiens	25-28
28039177-1	2017	Background: Anaplastic lymphoma kinase (ALK) inhibition using crizotinib has become the standard of care in advanced ALK-rearranged non-small cell lung cancer (NSCLC), but the treatment outcomes and duration of response vary widely.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	12-38
28039177-1	2017	Background: Anaplastic lymphoma kinase (ALK) inhibition using crizotinib has become the standard of care in advanced ALK-rearranged non-small cell lung cancer (NSCLC), but the treatment outcomes and duration of response vary widely.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	40-43
28039177-1	2017	Background: Anaplastic lymphoma kinase (ALK) inhibition using crizotinib has become the standard of care in advanced ALK-rearranged non-small cell lung cancer (NSCLC), but the treatment outcomes and duration of response vary widely.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	117-120
28039177-2	2017	Echinoderm microtubule-associated protein-like 4 (EML4)-ALK is the most common translocation, and the fusion variants show different sensitivity to crizotinib in vitro.	Crizotinib	148-158	EMAP like 4	Homo sapiens	0-48
28039177-2	2017	Echinoderm microtubule-associated protein-like 4 (EML4)-ALK is the most common translocation, and the fusion variants show different sensitivity to crizotinib in vitro.	Crizotinib	148-158	EMAP like 4	Homo sapiens	50-54
28039177-2	2017	Echinoderm microtubule-associated protein-like 4 (EML4)-ALK is the most common translocation, and the fusion variants show different sensitivity to crizotinib in vitro.	Crizotinib	148-158	ALK receptor tyrosine kinase	Homo sapiens	56-59
28039177-8	2017	The 2-year progression-free survival (PFS) rate was 76.0% [95% confidence interval (CI) 56.8-100] in group EML4-ALK variants 1/2/others versus 26.4% (95% CI 10.5-66.6) in group variants 3a/b (P = 0.034) among crizotinib-treated patients.	Crizotinib	209-219	EMAP like 4	Homo sapiens	107-111
28237354-0	2017	[Crizotinib for ROS1-rearranged non-small cell lung cancer patients].	Crizotinib	1-11	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	16-20
28237354-6	2017	Indeed, crizotinib has recently been approved in France in advanced ROS1-rearranged NSCLC.	Crizotinib	8-18	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	68-72
28342334-6	2017	The major clinical impact exerted by crizotinib represents the main reason for which not even a sole ROS1-positive tumor should be undetected.	Crizotinib	37-47	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	101-105
28427013-1	2017	The discovery of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) in 2007 led to the development and subsequent approval of the ALK inhibitor crizotinib in 2011.	Crizotinib	172-182	ALK receptor tyrosine kinase	Homo sapiens	17-43
28427013-1	2017	The discovery of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) in 2007 led to the development and subsequent approval of the ALK inhibitor crizotinib in 2011.	Crizotinib	172-182	ALK receptor tyrosine kinase	Homo sapiens	45-48
28427013-1	2017	The discovery of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) in 2007 led to the development and subsequent approval of the ALK inhibitor crizotinib in 2011.	Crizotinib	172-182	ALK receptor tyrosine kinase	Homo sapiens	158-161
28427013-4	2017	Ceritinib and the other next-generation ALK inhibitors are more potent than crizotinib and can overcome tumor cell resistance mechanisms.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	40-43
28035616-0	2017	Effects of Renal Function on Crizotinib Pharmacokinetics: Dose Recommendations for Patients with ALK-Positive Non-Small Cell Lung Cancer.	Crizotinib	29-39	ALK receptor tyrosine kinase	Homo sapiens	97-100
28035616-1	2017	BACKGROUND AND OBJECTIVES: Crizotinib (250 mg twice daily) is the first anaplastic lymphoma kinase (ALK) inhibitor approved for treatment of ALK-positive non-small-cell lung cancer (NSCLC).	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	72-98
28035616-1	2017	BACKGROUND AND OBJECTIVES: Crizotinib (250 mg twice daily) is the first anaplastic lymphoma kinase (ALK) inhibitor approved for treatment of ALK-positive non-small-cell lung cancer (NSCLC).	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	100-103
28035616-1	2017	BACKGROUND AND OBJECTIVES: Crizotinib (250 mg twice daily) is the first anaplastic lymphoma kinase (ALK) inhibitor approved for treatment of ALK-positive non-small-cell lung cancer (NSCLC).	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	141-144
29469073-3	2017	Here we report our experience with crizotinib in patients with advanced NSCLC harbouring ROS1 rearrangement.	Crizotinib	35-45	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	89-93
29469073-11	2017	In conclusion, crizotinib is effective with acceptable side effect profile in patients with ROS1 rearranged NSCLC in our population.	Crizotinib	15-25	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	92-96
28361443-0	2017	Gaining insight into crizotinib resistance mechanisms caused by L2026M and G2032R mutations in ROS1 via molecular dynamics simulations and free-energy calculations.	Crizotinib	21-31	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	95-99
28361443-2	2017	Crizotinib, a well-known drug approved by the FDA as an ALK inhibitor to treat advanced NSCLC, also shows potent inhibitoy activity against ROS1.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	56-59
28361443-2	2017	Crizotinib, a well-known drug approved by the FDA as an ALK inhibitor to treat advanced NSCLC, also shows potent inhibitoy activity against ROS1.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	140-144
28361443-4	2017	To provide insight into the mechanisms of this drug resistance, molecular dynamics simulations and free-energy calculations were carried out for complexes of crizotinib with wild-type (WT) ROS1 as well as the mutated L2026M and G2032R forms.	Crizotinib	158-168	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	189-193
28361443-6	2017	Binding free energy calculations showed that the L2026M and G2032R mutations significantly reduce the binding affinity of crizotinib for ROS1, and that the resistance to crizotinib caused by the L2026M and G2032R mutations arises mostly from increases in entropic terms.	Crizotinib	122-132	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	137-141
28007627-6	2017	Six of seven patients with ALK/KRAS co-alterations (86%) were primary refractory to crizotinib.	Crizotinib	84-94	ALK receptor tyrosine kinase	Homo sapiens	27-30
28007627-6	2017	Six of seven patients with ALK/KRAS co-alterations (86%) were primary refractory to crizotinib.	Crizotinib	84-94	KRAS proto-oncogene, GTPase	Homo sapiens	31-35
28007627-8	2017	Of the patients with ALK/EGFR co-alterations, one immediately progressed after receiving crizotinib for 1.3 months and two had a partial response for 5.7 and 7.3 months, respectively.	Crizotinib	89-99	ALK receptor tyrosine kinase	Homo sapiens	21-24
28007627-8	2017	Of the patients with ALK/EGFR co-alterations, one immediately progressed after receiving crizotinib for 1.3 months and two had a partial response for 5.7 and 7.3 months, respectively.	Crizotinib	89-99	epidermal growth factor receptor	Homo sapiens	25-29
28285684-0	2017	Dual occurrence of ALK G1202R solvent front mutation and small cell lung cancer transformation as resistance mechanisms to second generation ALK inhibitors without prior exposure to crizotinib.	Crizotinib	182-192	ALK receptor tyrosine kinase	Homo sapiens	19-22
28285691-1	2017	Treatment with the ALK inhibitor crizotinib has been associated with complex renal cyst formation in patients with non-small cell lung cancer (NSCLC).	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	19-22
28285691-3	2017	Patients with ALK-positive NSCLC treated with crizotinib were retrospectively identified from an institutional database.	Crizotinib	46-56	ALK receptor tyrosine kinase	Homo sapiens	14-17
28285695-0	2017	Optimal management of ALK-positive NSCLC progressing on crizotinib.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	22-25
28285695-1	2017	Crizotinib is an anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (-TKI) that represents the standard first-line treatment of patients with ALK-rearranged (ALK-positive) advanced non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	17-43
28285695-1	2017	Crizotinib is an anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (-TKI) that represents the standard first-line treatment of patients with ALK-rearranged (ALK-positive) advanced non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	45-48
28285695-1	2017	Crizotinib is an anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (-TKI) that represents the standard first-line treatment of patients with ALK-rearranged (ALK-positive) advanced non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	150-153
28285695-1	2017	Crizotinib is an anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (-TKI) that represents the standard first-line treatment of patients with ALK-rearranged (ALK-positive) advanced non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	150-153
28285695-5	2017	On the other hand, novel more potent and highly selective ALK-TKIs with demonstrated anti-tumor activity (CNS included) in crizotinib-refractory patients have been made available in recent years.	Crizotinib	123-133	ALK receptor tyrosine kinase	Homo sapiens	58-61
28285695-6	2017	Therefore, clinicians may well consider switching to a second-generation ALK-TKI as treatment option in case of progression on crizotinib.	Crizotinib	127-137	ALK receptor tyrosine kinase	Homo sapiens	73-76
28081478-6	2017	Response to ALK inhibitor crizotinib in a patient with ALK-rearranged PSC was evaluated according to the response evaluation criteria for solid tumors (RECIST) version 1.1.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	12-15
28081478-6	2017	Response to ALK inhibitor crizotinib in a patient with ALK-rearranged PSC was evaluated according to the response evaluation criteria for solid tumors (RECIST) version 1.1.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	55-58
28081478-12	2017	A 40-year-old woman diagnosed with ALK-rearranged PPC experienced a partial response (-32%) to the ALK inhibitor crizotinib.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	35-38
28081478-12	2017	A 40-year-old woman diagnosed with ALK-rearranged PPC experienced a partial response (-32%) to the ALK inhibitor crizotinib.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	99-102
28374971-1	2017	Crizotinib has achieved astonishing success in advanced non-small-cell lung cancer (NSCLC) patients harboring anaplastic lymphoma kinase (ALK) rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	110-136
28374971-1	2017	Crizotinib has achieved astonishing success in advanced non-small-cell lung cancer (NSCLC) patients harboring anaplastic lymphoma kinase (ALK) rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	138-141
28374971-8	2017	ALK-positive patients of 53.6% used crizotinib, whereas others only received chemotherapy (37.1%) or supportive care (9.3%).	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	0-3
28374971-9	2017	Usage of crizotinib prolonged PFS compared with chemotherapy in ALK-positive patients (median PFS 17.6 m vs. 4.8 m, P < 0.001).	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	64-67
28374971-11	2017	Crizotinib showed better PFS than chemotherapy in advanced ALK-positive NSCLC at any line.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	59-62
28374971-12	2017	However, half advanced ALK-positive patients never received crizotinib, which was grim and need improving.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	23-26
29872693-0	2017	ALKG1269A mutation as a potential mechanism of acquired resistance to crizotinib in an ALK-rearranged inflammatory myofibroblastic tumor.	Crizotinib	70-80	ALK receptor tyrosine kinase	Homo sapiens	0-3
29872693-2	2017	Treatment of this molecularly defined subgroup with the anaplastic lymphoma kinase inhibitor crizotinib has shown to be effective.	Crizotinib	93-103	ALK receptor tyrosine kinase	Homo sapiens	56-82
29872693-4	2017	Second generation anaplastic lymphoma kinase inhibitors such as ceritinib are able to overcome acquired resistance to crizotinib.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	18-44
29872693-5	2017	Here, we report the case of a patient with an inflammatory myofibroblastic tumors harboring a DCTN1-ALK fusion who developed resistance to crizotinib treatment.	Crizotinib	139-149	dynactin subunit 1	Homo sapiens	94-99
29872693-5	2017	Here, we report the case of a patient with an inflammatory myofibroblastic tumors harboring a DCTN1-ALK fusion who developed resistance to crizotinib treatment.	Crizotinib	139-149	ALK receptor tyrosine kinase	Homo sapiens	100-103
28178969-6	2017	In particular, for the latter, given the frequency of ALK gene deregulation in neuroblastoma patients, we discuss on second-generation ALK inhibitors in preclinical or clinical phases developed for the treatment of neuroblastoma patients resistant to crizotinib.We summarise how Omics drive clinical trials for neuroblastoma treatment and how much the research of biological targets is useful for personalised medicine.	Crizotinib	251-261	ALK receptor tyrosine kinase	Homo sapiens	135-138
28423535-0	2017	Overall survival with crizotinib and next-generation ALK inhibitors in ALK-positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide cohort retrospective study.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	71-74
28423535-1	2017	Overall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi) crizotinib in a large population of unselected patients with ALK-positive non-small-cell lung cancer (NSCLC) is not documented.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	31-57
28423535-1	2017	Overall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi) crizotinib in a large population of unselected patients with ALK-positive non-small-cell lung cancer (NSCLC) is not documented.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	59-62
28423535-1	2017	Overall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi) crizotinib in a large population of unselected patients with ALK-positive non-small-cell lung cancer (NSCLC) is not documented.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	75-78
28423535-9	2017	These patients had a median post-PD survival of 25.0 months and median OS from metastatic disease diagnosis of 89.6 months.Unselected ALK-positive NSCLC patients achieve good survival outcomes with crizotinib therapy.	Crizotinib	198-208	ALK receptor tyrosine kinase	Homo sapiens	134-137
27836576-7	2017	When the lung tumor of the mice treated with the ALK inhibitor crizotinib for 2 weeks was measured, tumor shrinkage was observed.	Crizotinib	63-73	anaplastic lymphoma kinase	Mus musculus	49-52
27836576-11	2017	Treatment of EML4-ALK tumor-bearing mice with crizotinib for 2 weeks induced dramatic shrinkage of tumors with no signs of toxicity.	Crizotinib	46-56	echinoderm microtubule associated protein like 4	Mus musculus	13-17
27836576-11	2017	Treatment of EML4-ALK tumor-bearing mice with crizotinib for 2 weeks induced dramatic shrinkage of tumors with no signs of toxicity.	Crizotinib	46-56	anaplastic lymphoma kinase	Mus musculus	18-21
28449509-7	2017	At nearly the same time, he was detected to have an ALK gene fusion mutation upon rebiopsy and subsequently began crizotinib therapy.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	52-55
29754556-0	2017	Responses to Crizotinib therapy in five patients with non-small-cell lung cancer who tested FISH negative and Ventana immunohistochemistry positive for ALK fusions.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	152-155
28245558-0	2017	L1198F Mutation Resensitizes Crizotinib to ALK by Altering the Conformation of Inhibitor and ATP Binding Sites.	Crizotinib	29-39	ALK receptor tyrosine kinase	Homo sapiens	43-46
28245558-2	2017	A recent study reported the newest generation inhibitor resistant mutation L1198F led to the resensitization to crizotinib, which is the first Food and Drug Administration (FDA) approved drug for the treatment of ALK-positive NSCLC.	Crizotinib	112-122	ALK receptor tyrosine kinase	Homo sapiens	213-216
28245558-5	2017	Our MD results revealed that L1198F mutation of ALK resulted in the conformational change at the inhibitor site and altered the binding affinity of ALK to crizotinib and lorlatinib.	Crizotinib	155-165	ALK receptor tyrosine kinase	Homo sapiens	48-51
28245558-5	2017	Our MD results revealed that L1198F mutation of ALK resulted in the conformational change at the inhibitor site and altered the binding affinity of ALK to crizotinib and lorlatinib.	Crizotinib	155-165	ALK receptor tyrosine kinase	Homo sapiens	148-151
28271038-0	2017	Successful crizotinib monotherapy in EGFR-mutant lung adenocarcinoma with acquired MET amplification after erlotinib therapy.	Crizotinib	11-21	epidermal growth factor receptor	Homo sapiens	37-41
28271038-6	2017	This is the first report of successful crizotinib single-agent therapy in EGFR-mutant NSCLC that acquired MET amplification during erlotinib therapy.	Crizotinib	39-49	epidermal growth factor receptor	Homo sapiens	74-78
28292264-8	2017	Crizotinib and AZD4547 exerted marked antitumor effects exclusively in PDX models with cMet (G30,G31) and FGFR2(G03) amplification.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	87-91
28292264-8	2017	Crizotinib and AZD4547 exerted marked antitumor effects exclusively in PDX models with cMet (G30,G31) and FGFR2(G03) amplification.	Crizotinib	0-10	fibroblast growth factor receptor 2	Homo sapiens	106-111
28292264-9	2017	Interestingly, synergistic antitumor activity was observed in G03 (FGFR2-amplifed and cMet non-amplified but IHC [2+]) with simultaneous treatment with Crizotinib and ADZ4547 at day 30 post-treatment.	Crizotinib	152-162	fibroblast growth factor receptor 2	Homo sapiens	67-72
28292264-9	2017	Interestingly, synergistic antitumor activity was observed in G03 (FGFR2-amplifed and cMet non-amplified but IHC [2+]) with simultaneous treatment with Crizotinib and ADZ4547 at day 30 post-treatment.	Crizotinib	152-162	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	86-90
28146421-10	2017	Tumor cells that had adapted through therapy exhibited elevated HGF expression and the c-MET inhibitor crizotinib enhanced AR42 pazopanib lethality in this evolved drug-resistant population.	Crizotinib	103-113	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	87-92
28409069-0	2017	Efficiency of Crizotinib on an ALK-Positive Inflammatory Myofibroblastic Tumor of the Central Nervous System: A Case Report.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	31-34
27865624-2	2017	Surprisingly, approximately 4 years after the discovery of ALK rearrangement in lung cancer, the first-in-class ALK inhibitor (ALKi), crizotinib, was approved for metastatic ALK-rearranged NSCLC by the US Food and Drug Administration.	Crizotinib	134-144	ALK receptor tyrosine kinase	Homo sapiens	59-62
27865624-2	2017	Surprisingly, approximately 4 years after the discovery of ALK rearrangement in lung cancer, the first-in-class ALK inhibitor (ALKi), crizotinib, was approved for metastatic ALK-rearranged NSCLC by the US Food and Drug Administration.	Crizotinib	134-144	ALK receptor tyrosine kinase	Homo sapiens	112-115
27865624-2	2017	Surprisingly, approximately 4 years after the discovery of ALK rearrangement in lung cancer, the first-in-class ALK inhibitor (ALKi), crizotinib, was approved for metastatic ALK-rearranged NSCLC by the US Food and Drug Administration.	Crizotinib	134-144	ALK receptor tyrosine kinase	Homo sapiens	112-115
28189201-0	2017	Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib.	Crizotinib	83-93	ALK receptor tyrosine kinase	Homo sapiens	49-52
28189201-1	2017	PURPOSE: To evaluate and compare the volumetric tumor burden changes during crizotinib therapy in mice and human cohorts with ALK-rearranged non-small-cell lung cancer (NSCLC).	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	126-129
28189201-8	2017	CONCLUSION: The present study described an initial attempt to evaluate quantitative tumor burden changes in co-clinical imaging studies of genomically-matched mice and human cohorts with ALK-rearranged NSCLC treated with crizotinib.	Crizotinib	221-231	ALK receptor tyrosine kinase	Homo sapiens	187-190
28337371-7	2017	In conclusion, our data illustrated that crizotinib combined with afatinib may be a potentially effective strategy for treating MPM patients with over-expression of MET and EGFR.	Crizotinib	41-51	epidermal growth factor receptor	Homo sapiens	173-177
28217366-0	2017	Crizotinib Inhibits Hyperpolarization-activated Cyclic Nucleotide-Gated Channel 4 Activity.	Crizotinib	0-10	hyperpolarization-activated, cyclic nucleotide-gated K+ 4	Mus musculus	20-81
27780368-1	2017	Alectinib is a highly selective second-generation ALK inhibitor that is active against most crizotinib ALK resistance mutations, with a good penetration in CNS and a good safety profile.	Crizotinib	92-102	ALK receptor tyrosine kinase	Homo sapiens	50-53
27912826-3	2017	Patients with tumors harboring such rearrangements are highly sensitive to ALK inhibitors, such as crizotinib, ceritinib, and alectinib.	Crizotinib	99-109	ALK receptor tyrosine kinase	Homo sapiens	75-78
27498387-0	2017	Sequential Therapy with Crizotinib and Alectinib in ALK-Rearranged Non-Small Cell Lung Cancer-A Multicenter Retrospective Study.	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	52-55
27498387-1	2017	INTRODUCTION: Alectinib and crizotinib have been approved for the therapy of NSCLC caused by anaplastic lymphoma kinase gene (ALK) rearrangement.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	93-119
27498387-1	2017	INTRODUCTION: Alectinib and crizotinib have been approved for the therapy of NSCLC caused by anaplastic lymphoma kinase gene (ALK) rearrangement.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	126-129
27863911-0	2017	Crizotinib for ROS1 patients: One small step in biomarker testing, one giant leap for advanced NSCLC patients.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	15-19
28167572-5	2017	The fusion gene enabled interleukin-3-independent growth of Ba/F3 cells and rendered them susceptible to the anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib and alectinib.	Crizotinib	163-173	interleukin 3	Mus musculus	24-37
28167572-10	2017	Constitutional activation of DCTN1-ALK fusion protein was suppressed by the anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib and alectinib.	Crizotinib	130-140	dynactin subunit 1	Homo sapiens	29-34
28167572-10	2017	Constitutional activation of DCTN1-ALK fusion protein was suppressed by the anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib and alectinib.	Crizotinib	130-140	ALK receptor tyrosine kinase	Homo sapiens	35-38
27526341-0	2017	Fluorescence spectroscopic and molecular docking studies of the binding interaction between the new anaplastic lymphoma kinase inhibitor crizotinib and bovine serum albumin.	Crizotinib	137-147	albumin	Homo sapiens	159-172
27526341-1	2017	Binding of the recently introduced anti-cancer drug, crizotinib (CRB) with the bovine serum albumin (BSA) was comprehensively studied with the aid of fluorescence and UV-Vis spectroscopic as well as molecular docking techniques.	Crizotinib	53-63	albumin	Homo sapiens	86-99
27526341-1	2017	Binding of the recently introduced anti-cancer drug, crizotinib (CRB) with the bovine serum albumin (BSA) was comprehensively studied with the aid of fluorescence and UV-Vis spectroscopic as well as molecular docking techniques.	Crizotinib	65-68	albumin	Homo sapiens	86-99
28032129-13	2017	Steady-state trough-free crizotinib concentrations in plasma at the MTD exceed inhibitory concentrations of crizotinib in ALCL cell lines.	Crizotinib	25-35	metallothionein 1E	Homo sapiens	68-71
28209203-2	2017	An increased incidence of renal cystic lesions, often with features concerning for malignancy or infection, has been reported in patients with anaplastic lymphoma kinase (ALK) - rearranged advanced non-small cell lung cancer (NSCLC) treated with Crizotinib.	Crizotinib	246-256	ALK receptor tyrosine kinase	Homo sapiens	143-169
28209203-2	2017	An increased incidence of renal cystic lesions, often with features concerning for malignancy or infection, has been reported in patients with anaplastic lymphoma kinase (ALK) - rearranged advanced non-small cell lung cancer (NSCLC) treated with Crizotinib.	Crizotinib	246-256	ALK receptor tyrosine kinase	Homo sapiens	171-174
27768922-1	2017	Currently, crizotinib is the first generation drug, which has been used in the treatment of ALK-rearranged non-small cell lung cancer (NSCLC).	Crizotinib	11-21	ALK receptor tyrosine kinase	Rattus norvegicus	92-95
27838320-1	2017	As the key chiral precursor of Crizotinib (S)-1-(2,6-dichloro-3-fluorophenyl) phenethyl alcohol can be prepared from 1-(2,6-dichloro-3-fluorophenyl) acetophenone by the reductive coupling reactions of alcohol dehydrogenase (ADH) and glucose dehydrogenases (GDH).	Crizotinib	31-41	Alcohol dehydrogenase	Escherichia coli	201-222
27783866-0	2017	Amphiregulin triggered epidermal growth factor receptor activation confers in vivo crizotinib-resistance of EML4-ALK lung cancer and circumvention by epidermal growth factor receptor inhibitors.	Crizotinib	83-93	amphiregulin	Mus musculus	0-12
27783866-0	2017	Amphiregulin triggered epidermal growth factor receptor activation confers in vivo crizotinib-resistance of EML4-ALK lung cancer and circumvention by epidermal growth factor receptor inhibitors.	Crizotinib	83-93	epidermal growth factor receptor	Mus musculus	23-55
27783866-1	2017	Crizotinib, a first-generation anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor, is known to be effective against echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive non-small cell lung cancers.	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	31-57
27783866-1	2017	Crizotinib, a first-generation anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor, is known to be effective against echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive non-small cell lung cancers.	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	59-62
27783866-1	2017	Crizotinib, a first-generation anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor, is known to be effective against echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive non-small cell lung cancers.	Crizotinib	0-10	echinoderm microtubule associated protein like 4	Mus musculus	124-172
27783866-1	2017	Crizotinib, a first-generation anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor, is known to be effective against echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive non-small cell lung cancers.	Crizotinib	0-10	echinoderm microtubule associated protein like 4	Mus musculus	174-178
27783866-1	2017	Crizotinib, a first-generation anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor, is known to be effective against echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive non-small cell lung cancers.	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	180-183
27783866-4	2017	In this study, we established crizotinib-resistant cells (A925LPE3-CR) via long-term administration of crizotinib to a mouse model of pleural carcinomatous effusions; this model involved implantation of the A925LPE3 cell line, which harbors the EML4-ALK gene rearrangement.	Crizotinib	30-40	echinoderm microtubule associated protein like 4	Mus musculus	245-249
28217366-1	2017	BACKGROUND: Sinus bradycardia is frequently observed in patients treated with crizotinib, a receptor tyrosine kinase inhibitor used for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC).	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	153-179
28217366-1	2017	BACKGROUND: Sinus bradycardia is frequently observed in patients treated with crizotinib, a receptor tyrosine kinase inhibitor used for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC).	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	181-184
28217366-7	2017	Crizotinib resulted in diminished current density of HCN4, the major molecular determinant of If, with an IC50 of 1.4 +- 0.3 mumol/L.	Crizotinib	0-10	hyperpolarization-activated, cyclic nucleotide-gated K+ 4	Mus musculus	53-57
28217366-8	2017	Crizotinib also slowed HCN4 activation and shifted the activation curve to the left towards more hyperpolarized potentials.	Crizotinib	0-10	hyperpolarization-activated, cyclic nucleotide-gated K+ 4	Mus musculus	23-27
28217366-9	2017	CONCLUSIONS: Our results suggest that crizotinib"s effects on HCN4 channels play a significant role in mediating its observed effects on HR.	Crizotinib	38-48	hyperpolarization-activated, cyclic nucleotide-gated K+ 4	Mus musculus	62-66
28050598-5	2017	Three of these-crizotinib, ceritinib, and alectinib-are now FDA approved for the treatment of metastatic NSCLC positive for ALK fusions.	Crizotinib	15-25	ALK receptor tyrosine kinase	Homo sapiens	124-127
27783866-4	2017	In this study, we established crizotinib-resistant cells (A925LPE3-CR) via long-term administration of crizotinib to a mouse model of pleural carcinomatous effusions; this model involved implantation of the A925LPE3 cell line, which harbors the EML4-ALK gene rearrangement.	Crizotinib	30-40	anaplastic lymphoma kinase	Mus musculus	250-253
27783866-6	2017	In cell clone #2, which is one of the clones of A925LPE3-CR, crizotinib sensitivity was restored via the inhibition of epidermal growth factor receptor (EGFR) by means of an EGFR tyrosine-kinase inhibitor (erlotinib) or an anti-EGFR antibody (cetuximab) in vitro and in the murine xenograft model.	Crizotinib	61-71	epidermal growth factor receptor	Mus musculus	119-151
27783866-6	2017	In cell clone #2, which is one of the clones of A925LPE3-CR, crizotinib sensitivity was restored via the inhibition of epidermal growth factor receptor (EGFR) by means of an EGFR tyrosine-kinase inhibitor (erlotinib) or an anti-EGFR antibody (cetuximab) in vitro and in the murine xenograft model.	Crizotinib	61-71	epidermal growth factor receptor	Mus musculus	153-157
27783866-6	2017	In cell clone #2, which is one of the clones of A925LPE3-CR, crizotinib sensitivity was restored via the inhibition of epidermal growth factor receptor (EGFR) by means of an EGFR tyrosine-kinase inhibitor (erlotinib) or an anti-EGFR antibody (cetuximab) in vitro and in the murine xenograft model.	Crizotinib	61-71	epidermal growth factor receptor	Mus musculus	174-178
27783866-6	2017	In cell clone #2, which is one of the clones of A925LPE3-CR, crizotinib sensitivity was restored via the inhibition of epidermal growth factor receptor (EGFR) by means of an EGFR tyrosine-kinase inhibitor (erlotinib) or an anti-EGFR antibody (cetuximab) in vitro and in the murine xenograft model.	Crizotinib	61-71	epidermal growth factor receptor	Mus musculus	174-178
27783866-8	2017	A knockdown of AREG with small interfering RNAs restored the sensitivity to crizotinib.	Crizotinib	76-86	amphiregulin	Mus musculus	15-19
27783866-9	2017	These data suggest that overexpression of EGFR ligands such as AREG can cause resistance to crizotinib, and that inhibition of EGFR signaling may be a promising strategy to overcome crizotinib resistance in EML4-ALK lung cancer.	Crizotinib	92-102	epidermal growth factor receptor	Mus musculus	42-46
27783866-9	2017	These data suggest that overexpression of EGFR ligands such as AREG can cause resistance to crizotinib, and that inhibition of EGFR signaling may be a promising strategy to overcome crizotinib resistance in EML4-ALK lung cancer.	Crizotinib	92-102	amphiregulin	Mus musculus	63-67
27783866-9	2017	These data suggest that overexpression of EGFR ligands such as AREG can cause resistance to crizotinib, and that inhibition of EGFR signaling may be a promising strategy to overcome crizotinib resistance in EML4-ALK lung cancer.	Crizotinib	182-192	amphiregulin	Mus musculus	63-67
27783866-9	2017	These data suggest that overexpression of EGFR ligands such as AREG can cause resistance to crizotinib, and that inhibition of EGFR signaling may be a promising strategy to overcome crizotinib resistance in EML4-ALK lung cancer.	Crizotinib	182-192	epidermal growth factor receptor	Mus musculus	127-131
27804873-4	2017	Since the first ALK inhibitor, crizotinib, was approved by the US Food and Drug Administration (FDA) for the treatment of NSCLC patients in 2011, ALK has been identified as a promising target for NSCLC therapy.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	16-19
27804873-4	2017	Since the first ALK inhibitor, crizotinib, was approved by the US Food and Drug Administration (FDA) for the treatment of NSCLC patients in 2011, ALK has been identified as a promising target for NSCLC therapy.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	146-149
28365967-0	2017	Complete response to crizotinib in a patient with adenocarcinoma of the lung cancer harboring c- MET amplification.	Crizotinib	21-31	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	94-100
29199685-3	2017	Crizotinib is a drug which shows its anti-tumoral effect in cMET positive cases.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	60-64
29199685-4	2017	Here we present a case series of three such patients who achieved were cMET amplified and showed partial response on Crizotinib.	Crizotinib	117-127	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	71-75
29199691-3	2017	Here we present an analysis of clinicopathological profile of patients of metastatic adenocarcinoma harboring the ALK-EML4 fusion gene and their response to targeted therapy in the form of crizotinib.	Crizotinib	189-199	ALK receptor tyrosine kinase	Homo sapiens	114-117
29199691-3	2017	Here we present an analysis of clinicopathological profile of patients of metastatic adenocarcinoma harboring the ALK-EML4 fusion gene and their response to targeted therapy in the form of crizotinib.	Crizotinib	189-199	EMAP like 4	Homo sapiens	118-122
27614248-0	2017	Combinational Analysis of FISH and Immunohistochemistry Reveals Rare Genomic Events in ALK Fusion Patterns in NSCLC that Responds to Crizotinib Treatment.	Crizotinib	133-143	ALK receptor tyrosine kinase	Homo sapiens	87-90
29279550-8	2017	For targeted therapies, an anti-CD30 monoclonal antibody linked to a synthetic antimitotic agent (brentuximab vedotin) and ALK inhibitors (crizotinib, alectinib, and ceritinib) are being used in clinical settings.	Crizotinib	139-149	TNF receptor superfamily member 8	Homo sapiens	32-36
28868517-0	2017	Chart review versus an automated bioinformatic approach to assess real-world crizotinib effectiveness in ALK-positive NSCLC.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	105-108
29333528-0	2017	Patterns of Metastatic Spread and Mechanisms of Resistance to Crizotinib in ROS1-Positive Non-Small-Cell Lung Cancer.	Crizotinib	62-72	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	76-80
29333528-1	2017	PURPOSE: The ROS1 tyrosine kinase is activated through ROS1 gene rearrangements in 1-2% of non-small cell lung cancer (NSCLC), conferring sensitivity to treatment with the ALK/ROS1/MET inhibitor crizotinib.	Crizotinib	195-205	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	13-17
29333528-1	2017	PURPOSE: The ROS1 tyrosine kinase is activated through ROS1 gene rearrangements in 1-2% of non-small cell lung cancer (NSCLC), conferring sensitivity to treatment with the ALK/ROS1/MET inhibitor crizotinib.	Crizotinib	195-205	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	55-59
29333528-1	2017	PURPOSE: The ROS1 tyrosine kinase is activated through ROS1 gene rearrangements in 1-2% of non-small cell lung cancer (NSCLC), conferring sensitivity to treatment with the ALK/ROS1/MET inhibitor crizotinib.	Crizotinib	195-205	ALK receptor tyrosine kinase	Homo sapiens	172-175
29333528-1	2017	PURPOSE: The ROS1 tyrosine kinase is activated through ROS1 gene rearrangements in 1-2% of non-small cell lung cancer (NSCLC), conferring sensitivity to treatment with the ALK/ROS1/MET inhibitor crizotinib.	Crizotinib	195-205	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	55-59
29333528-2	2017	Currently, insights into patterns of metastatic spread and mechanisms of crizotinib resistance among ROS1-positive patients are limited.	Crizotinib	73-83	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	101-105
29333528-7	2017	Despite similar overall survival between ALK- and ROS1-positive patients treated with crizotinib (median 3.0 versus 2.5 years, respectively; P=0.786), ROS1-positive patients also had a significantly lower cumulative incidence of brain metastases (34% vs. 73% at 5 years; P<0.0001).	Crizotinib	86-96	ALK receptor tyrosine kinase	Homo sapiens	41-44
29333528-7	2017	Despite similar overall survival between ALK- and ROS1-positive patients treated with crizotinib (median 3.0 versus 2.5 years, respectively; P=0.786), ROS1-positive patients also had a significantly lower cumulative incidence of brain metastases (34% vs. 73% at 5 years; P<0.0001).	Crizotinib	86-96	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	50-54
29333528-12	2017	ROS1 resistance mutations, particularly G2032R, appear to be the predominant mechanism of resistance to crizotinib, underscoring the need to develop novel ROS1 inhibitors with activity against these resistant mutants.	Crizotinib	104-114	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	0-4
29333528-12	2017	ROS1 resistance mutations, particularly G2032R, appear to be the predominant mechanism of resistance to crizotinib, underscoring the need to develop novel ROS1 inhibitors with activity against these resistant mutants.	Crizotinib	104-114	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	155-159
29527595-0	2017	Dramatic Response to Crizotinib in a Patient with Lung Cancer Positive for an HLA-DRB1-MET Gene Fusion.	Crizotinib	21-31	major histocompatibility complex, class II, DR beta 1	Homo sapiens	78-86
27697581-11	2017	Two patients whose tumors harbored activating EGFR mutations achieved confirmed partial responses, one at each crizotinib dose level.	Crizotinib	111-121	epidermal growth factor receptor	Homo sapiens	46-50
27707887-1	2017	Activation of the EGFR pathway is one of the mechanisms inducing acquired resistance to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) such as crizotinib and alectinib.	Crizotinib	162-172	epidermal growth factor receptor	Homo sapiens	18-22
27707887-1	2017	Activation of the EGFR pathway is one of the mechanisms inducing acquired resistance to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) such as crizotinib and alectinib.	Crizotinib	162-172	ALK receptor tyrosine kinase	Homo sapiens	88-114
27707887-1	2017	Activation of the EGFR pathway is one of the mechanisms inducing acquired resistance to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) such as crizotinib and alectinib.	Crizotinib	162-172	ALK receptor tyrosine kinase	Homo sapiens	116-119
28766541-0	2017	[Use of crizotinib for refractory ALK-positive lymphomas].	Crizotinib	8-18	ALK receptor tyrosine kinase	Homo sapiens	34-37
28118634-1	2017	BACKGROUND: Presence of anaplastic lymphoma kinase (ALK) rearrangement is an indication for crizotinib in the treatment of patients with advanced or metastatic lung adenocarcinoma.	Crizotinib	92-102	ALK receptor tyrosine kinase	Homo sapiens	24-50
28118634-1	2017	BACKGROUND: Presence of anaplastic lymphoma kinase (ALK) rearrangement is an indication for crizotinib in the treatment of patients with advanced or metastatic lung adenocarcinoma.	Crizotinib	92-102	ALK receptor tyrosine kinase	Homo sapiens	52-55
28766541-1	2017	AIM: To evaluate the safety and efficacy of crizotinib used in pediatric patients with relapsed or refractory ALK-positive anaplastic large-cell lymphoma (ALCL).	Crizotinib	44-54	ALK receptor tyrosine kinase	Homo sapiens	110-113
28766541-2	2017	SUBJECTS AND METHODS: The paper describes the experience with crizotinib used in 8 patients with refractory ALK-ALCL before and after allogeneic hematopoietic stem cell transplantation (HSCT).	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	108-111
28766541-4	2017	CONCLUSION: Low and manageable toxicity of crizotinib and complete PET-negative responses in patients with resistant ALK lymphomas favor the need to test the drug as first-line therapy, by possibly decreasing the intensification of chemotherapy.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	117-120
27835868-0	2016	Clinical data from the real world: efficacy of Crizotinib in Chinese patients with advanced ALK-rearranged non-small cell lung cancer and brain metastases.	Crizotinib	47-57	ALK receptor tyrosine kinase	Homo sapiens	92-95
27835868-2	2016	Crizotinib is a small-molecule tyrosine kinase inhibitor (TKI) for ALK-rearranged NSCLC patients.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	67-70
27835868-3	2016	Herein, we conducted a retrospective study to explore how Crizotinib affects the control of brain metastases and the overall prognosis in advanced ALK-rearranged NSCLC patients with brain metastases in Chinese population.	Crizotinib	58-68	ALK receptor tyrosine kinase	Homo sapiens	147-150
27835868-7	2016	In conclusion, ALK-rearranged NSCLC patients with brain metastases before Crizotinib may benefit more from Crizotinib than those developing brain metastases during Crizotinib treatment.	Crizotinib	74-84	ALK receptor tyrosine kinase	Homo sapiens	15-18
27835868-7	2016	In conclusion, ALK-rearranged NSCLC patients with brain metastases before Crizotinib may benefit more from Crizotinib than those developing brain metastases during Crizotinib treatment.	Crizotinib	107-117	ALK receptor tyrosine kinase	Homo sapiens	15-18
27835868-7	2016	In conclusion, ALK-rearranged NSCLC patients with brain metastases before Crizotinib may benefit more from Crizotinib than those developing brain metastases during Crizotinib treatment.	Crizotinib	107-117	ALK receptor tyrosine kinase	Homo sapiens	15-18
27401242-0	2016	Crizotinib-Resistant ROS1 Mutations Reveal a Predictive Kinase Inhibitor Sensitivity Model for ROS1- and ALK-Rearranged Lung Cancers.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	21-25
27753543-0	2016	STAT3-targeted treatment with silibinin overcomes the acquired resistance to crizotinib in ALK-rearranged lung cancer.	Crizotinib	77-87	signal transducer and activator of transcription 3	Homo sapiens	0-5
27753543-0	2016	STAT3-targeted treatment with silibinin overcomes the acquired resistance to crizotinib in ALK-rearranged lung cancer.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	91-94
27753543-2	2016	Using a model of anaplastic lymphoma kinase gene (ALK)-translocated NSCLC with acquired resistance to the ALK TKI crizotinib, but lacking amplifications or mutations in the kinase domain of ALK, we herein present evidence that STAT3 activation is a novel mechanism of crizotinib resistance that involves the upregulation of immune escape and epithelial to mesenchymal transition (EMT) signaling pathways.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	50-53
27753543-2	2016	Using a model of anaplastic lymphoma kinase gene (ALK)-translocated NSCLC with acquired resistance to the ALK TKI crizotinib, but lacking amplifications or mutations in the kinase domain of ALK, we herein present evidence that STAT3 activation is a novel mechanism of crizotinib resistance that involves the upregulation of immune escape and epithelial to mesenchymal transition (EMT) signaling pathways.	Crizotinib	268-278	ALK receptor tyrosine kinase	Homo sapiens	50-53
27753543-3	2016	Taking advantage of the flavonolignan silibinin as a naturally occurring STAT3-targeted pharmacological inhibitor, we confirmed that STAT3 activation protects ALK-translocated NSCLC from crizotinib.	Crizotinib	187-197	signal transducer and activator of transcription 3	Homo sapiens	133-138
27753543-3	2016	Taking advantage of the flavonolignan silibinin as a naturally occurring STAT3-targeted pharmacological inhibitor, we confirmed that STAT3 activation protects ALK-translocated NSCLC from crizotinib.	Crizotinib	187-197	ALK receptor tyrosine kinase	Homo sapiens	159-162
27753543-4	2016	Accordingly, silibinin-induced inhibition of STAT3 worked synergistically with crizotinib to reverse acquired resistance and restore sensitivity in crizotinib-resistant cells.	Crizotinib	148-158	signal transducer and activator of transcription 3	Homo sapiens	45-50
27753543-5	2016	Moreover, silibinin treatment significantly inhibited the upregulation of the immune checkpoint regulator PD-L1 and also EMT regulators (e.g., SLUG, VIM, CD44) in crizotinib-refractory cells.	Crizotinib	163-173	CD274 molecule	Homo sapiens	106-111
27753543-5	2016	Moreover, silibinin treatment significantly inhibited the upregulation of the immune checkpoint regulator PD-L1 and also EMT regulators (e.g., SLUG, VIM, CD44) in crizotinib-refractory cells.	Crizotinib	163-173	snail family transcriptional repressor 2	Homo sapiens	143-147
27753543-5	2016	Moreover, silibinin treatment significantly inhibited the upregulation of the immune checkpoint regulator PD-L1 and also EMT regulators (e.g., SLUG, VIM, CD44) in crizotinib-refractory cells.	Crizotinib	163-173	vimentin	Homo sapiens	149-152
27753543-5	2016	Moreover, silibinin treatment significantly inhibited the upregulation of the immune checkpoint regulator PD-L1 and also EMT regulators (e.g., SLUG, VIM, CD44) in crizotinib-refractory cells.	Crizotinib	163-173	CD44 molecule (Indian blood group)	Homo sapiens	154-158
27401242-0	2016	Crizotinib-Resistant ROS1 Mutations Reveal a Predictive Kinase Inhibitor Sensitivity Model for ROS1- and ALK-Rearranged Lung Cancers.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	95-99
27401242-3	2016	Only two mutations in the ROS1 kinase domain responsible for crizotinib resistance have been described in patients thus far.	Crizotinib	61-71	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	26-30
27401242-4	2016	METHODS: A patient suffering from a metastatic NSCLC harboring an ezrin (EZR)-ROS1 fusion gene developed acquired resistance to the ALK/ROS1 inhibitor crizotinib.	Crizotinib	151-161	ezrin	Homo sapiens	66-71
27401242-4	2016	METHODS: A patient suffering from a metastatic NSCLC harboring an ezrin (EZR)-ROS1 fusion gene developed acquired resistance to the ALK/ROS1 inhibitor crizotinib.	Crizotinib	151-161	ezrin	Homo sapiens	73-76
27401242-4	2016	METHODS: A patient suffering from a metastatic NSCLC harboring an ezrin (EZR)-ROS1 fusion gene developed acquired resistance to the ALK/ROS1 inhibitor crizotinib.	Crizotinib	151-161	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	78-82
27401242-4	2016	METHODS: A patient suffering from a metastatic NSCLC harboring an ezrin (EZR)-ROS1 fusion gene developed acquired resistance to the ALK/ROS1 inhibitor crizotinib.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	132-135
27401242-4	2016	METHODS: A patient suffering from a metastatic NSCLC harboring an ezrin (EZR)-ROS1 fusion gene developed acquired resistance to the ALK/ROS1 inhibitor crizotinib.	Crizotinib	151-161	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	136-140
27401242-8	2016	Functional in vitro studies demonstrated that ROS1 harboring either the S1986Y or the S1986F mutation, while conferring resistance to crizotinib and ceritinib, was inhibited by lorlatinib (PF-06463922).	Crizotinib	134-144	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	46-50
27401242-12	2016	CONCLUSIONS: Clinical evidence, in vitro validation, and homology-based prediction provide guidance for treatment decision making for patients with ROS1-rearranged NSCLC who progressed on crizotinib.	Crizotinib	188-198	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	148-152
27835601-0	2016	Is there a benefit of first- or second-line crizotinib in locally advanced or metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer?	Crizotinib	44-54	ALK receptor tyrosine kinase	Homo sapiens	89-115
28018791-2	2016	It inhibits two of the most common ALK-mutants that confer resistance to crizotinib.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	35-38
28008383-1	2016	AIM: To investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination studies.	Crizotinib	74-84	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	59-63
27835601-2	2016	BACKGROUND: Crizotinib show a promising efficacy in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	66-92
27835601-2	2016	BACKGROUND: Crizotinib show a promising efficacy in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	94-97
27835601-10	2016	CONCLUSIONS: First-line crizotinib may more effective than second-line crizotinib for patients with locally advanced or metastatic ALK-positive NSCLC.	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	131-134
27835601-10	2016	CONCLUSIONS: First-line crizotinib may more effective than second-line crizotinib for patients with locally advanced or metastatic ALK-positive NSCLC.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	131-134
28174489-0	2016	ALK gene expression status in pleural effusion predicts tumor responsiveness to crizotinib in Chinese patients with lung adenocarcinoma.	Crizotinib	80-90	ALK receptor tyrosine kinase	Homo sapiens	0-3
27917934-7	2016	In in vitro study, inhibition of c-MET using c-MET inhibitors (SU11274 or crizotinib) significantly decreased the proliferation, and increased the apoptosis of OCCC cells.	Crizotinib	74-84	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	33-38
27917934-7	2016	In in vitro study, inhibition of c-MET using c-MET inhibitors (SU11274 or crizotinib) significantly decreased the proliferation, and increased the apoptosis of OCCC cells.	Crizotinib	74-84	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	45-50
28174489-7	2016	CONCLUSIONS: The ALK gene expression status detected by the Ventana IHC ALK (D5F3) platform in MPE samples may predict tumor responsiveness to crizotinib in Chinese patients with advanced lung adenocarcinoma.	Crizotinib	143-153	ALK receptor tyrosine kinase	Homo sapiens	17-20
28174489-7	2016	CONCLUSIONS: The ALK gene expression status detected by the Ventana IHC ALK (D5F3) platform in MPE samples may predict tumor responsiveness to crizotinib in Chinese patients with advanced lung adenocarcinoma.	Crizotinib	143-153	ALK receptor tyrosine kinase	Homo sapiens	72-75
27744726-2	2016	Unfortunately most patients develop disease progression in less than a year of treatment with crizotinib, the first-generation ALK-inhibitor.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	127-130
28050149-1	2016	BACKGROUND: Crizotinib was the first agent approved for the treatment of anaplastic lymphoma kinase (ALK)-positive (+) non-small-cell lung cancer (nsclc), followed by ceritinib.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	73-99
28050149-1	2016	BACKGROUND: Crizotinib was the first agent approved for the treatment of anaplastic lymphoma kinase (ALK)-positive (+) non-small-cell lung cancer (nsclc), followed by ceritinib.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	101-104
28050149-3	2016	With limited real-world data available, the objective of the present work was to evaluate treatment patterns and survival after crizotinib in patients with locally advanced or metastatic ALK+ nsclc in Canada.	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	187-190
28050149-12	2016	CONCLUSIONS: A substantial proportion of patients with ALK+ nsclc received no further treatment or died before receiving additional treatment after crizotinib.	Crizotinib	148-158	ALK receptor tyrosine kinase	Homo sapiens	55-58
27682212-1	2016	INTRODUCTION: The treatment of patients with ALK-rearranged non-small-cell lung cancer was completely revolutionized by the introduction of Crizotinib, a small molecule inhibiting ALK, MET and ROS1.	Crizotinib	140-150	ALK receptor tyrosine kinase	Homo sapiens	45-48
27682212-1	2016	INTRODUCTION: The treatment of patients with ALK-rearranged non-small-cell lung cancer was completely revolutionized by the introduction of Crizotinib, a small molecule inhibiting ALK, MET and ROS1.	Crizotinib	140-150	ALK receptor tyrosine kinase	Homo sapiens	180-183
27744726-4	2016	Expert commentary: Second generation ALK inhibitors as alectinib and ceritinib can overcome crizotinib-resistant mutations and improve central nervous system control.	Crizotinib	92-102	ALK receptor tyrosine kinase	Homo sapiens	37-40
27682212-1	2016	INTRODUCTION: The treatment of patients with ALK-rearranged non-small-cell lung cancer was completely revolutionized by the introduction of Crizotinib, a small molecule inhibiting ALK, MET and ROS1.	Crizotinib	140-150	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	193-197
27682212-6	2016	Expert opinion: The better characterization of the mechanisms of resistance to Crizotinib led to the development of newest drugs, which are active both after Crizotinib failure and in patients naive from ALK-inhibitors.	Crizotinib	79-89	ALK receptor tyrosine kinase	Homo sapiens	204-207
27836716-17	2016	51 (72% [60-82]) of 71 patients with ALK-rearranged NSCLC with previous crizotinib treatment had an objective response (44 [62% (50-73)] had a confirmed objective response).	Crizotinib	72-82	ALK receptor tyrosine kinase	Homo sapiens	37-40
27863201-13	2016	Conclusion Alectinib showed good efficacy against CNS metastases, in addition to systemic activity, in crizotinib-refractory ALK-positive NSCLC.	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	125-128
27613526-0	2016	An Anaplastic Lymphoma Kinase Immunohistochemistry-Negative but Fluorescence In Situ Hybridization-Positive Lung Adenocarcinoma Is Resistant to Crizotinib.	Crizotinib	144-154	ALK receptor tyrosine kinase	Homo sapiens	3-29
27613526-3	2016	We report here an ALK FISH-positive patient-derived xenograft (PDX) that was nonresponsive to crizotinib therapy.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	18-21
27836716-18	2016	All eight crizotinib-naive patients with ALK-rearranged NSCLC had a confirmed objective response (100% [63-100]).	Crizotinib	10-20	ALK receptor tyrosine kinase	Homo sapiens	41-44
27836716-25	2016	A randomised phase 2 trial in patients with crizotinib-resistant ALK-rearranged NSCLC is prospectively assessing the safety and efficacy of two regimens assessed in the phase 2 portion of this trial (90 mg once daily and 180 mg once daily with a 7 day lead-in at 90 mg).	Crizotinib	44-54	ALK receptor tyrosine kinase	Homo sapiens	65-68
27965961-2	2016	The ALK inhibitor crizotinib has led to improved outcomes in the first- and second-line setting; however, toxicities, intracranial activity, and acquired resistance necessitated the advent of later generation ALK inhibitors.	Crizotinib	18-28	ALK receptor tyrosine kinase	Homo sapiens	4-7
28149753-5	2016	Crizotinib, the first ALK inhibitor (ALK-I) licensed in clinical practice, is the standard of care for newly diagnosed patients.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	22-25
28149753-5	2016	Crizotinib, the first ALK inhibitor (ALK-I) licensed in clinical practice, is the standard of care for newly diagnosed patients.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	37-40
27965961-4	2016	Alectinib is a second-generation ALK inhibitor capable of overcoming multiple crizotinib-resistant ALK mutations and has demonstrated improved outcomes after crizotinib failure.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	33-36
27965961-4	2016	Alectinib is a second-generation ALK inhibitor capable of overcoming multiple crizotinib-resistant ALK mutations and has demonstrated improved outcomes after crizotinib failure.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	99-102
27863497-6	2016	Consequently, we diagnosed the case as ALK-positive rendering the patient eligible to crizotinib treatment.	Crizotinib	86-96	ALK receptor tyrosine kinase	Homo sapiens	39-42
27780853-1	2016	PURPOSE: Non-small cell lung cancers (NSCLCs) harboring ALK gene rearrangements (ALK+) typically become resistant to the first-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) crizotinib through development of secondary resistance mutations in ALK or disease progression in the brain.	Crizotinib	203-213	ALK receptor tyrosine kinase	Homo sapiens	56-59
27780853-1	2016	PURPOSE: Non-small cell lung cancers (NSCLCs) harboring ALK gene rearrangements (ALK+) typically become resistant to the first-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) crizotinib through development of secondary resistance mutations in ALK or disease progression in the brain.	Crizotinib	203-213	ALK receptor tyrosine kinase	Homo sapiens	81-84
27780853-1	2016	PURPOSE: Non-small cell lung cancers (NSCLCs) harboring ALK gene rearrangements (ALK+) typically become resistant to the first-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) crizotinib through development of secondary resistance mutations in ALK or disease progression in the brain.	Crizotinib	203-213	ALK receptor tyrosine kinase	Homo sapiens	138-164
27780853-1	2016	PURPOSE: Non-small cell lung cancers (NSCLCs) harboring ALK gene rearrangements (ALK+) typically become resistant to the first-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) crizotinib through development of secondary resistance mutations in ALK or disease progression in the brain.	Crizotinib	203-213	ALK receptor tyrosine kinase	Homo sapiens	81-84
27780853-1	2016	PURPOSE: Non-small cell lung cancers (NSCLCs) harboring ALK gene rearrangements (ALK+) typically become resistant to the first-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) crizotinib through development of secondary resistance mutations in ALK or disease progression in the brain.	Crizotinib	203-213	ALK receptor tyrosine kinase	Homo sapiens	81-84
27732954-2	2016	However, clinical trials reveal that a limited proportion of ALK-positive neuroblastoma patients experience clinical benefits from Crizotinib, a clinically approved specific inhibitor of ALK.	Crizotinib	131-141	ALK receptor tyrosine kinase	Homo sapiens	61-64
27732954-2	2016	However, clinical trials reveal that a limited proportion of ALK-positive neuroblastoma patients experience clinical benefits from Crizotinib, a clinically approved specific inhibitor of ALK.	Crizotinib	131-141	ALK receptor tyrosine kinase	Homo sapiens	187-190
27732954-4	2016	Here, we describe a deep quantitative phosphoproteomic approach in which Crizotinib-treated neuroblastoma cell lines bearing aberrant ALK are used to investigate downstream regulated phosphoproteins.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	134-137
27738334-0	2016	Efficacy of crizotinib and pemetrexed-based chemotherapy in Chinese NSCLC patients with ROS1 rearrangement.	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	88-92
27738334-2	2016	This study aimed to investigate the efficacy of crizotinib and pemetrexed-based chemotherapy in Chinese NSCLC patients with ROS1 rearrangement.	Crizotinib	48-58	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	124-128
27738334-11	2016	CONCLUSIONS: Crizotinib was also highly active at treating Chinese NSCLC patients with ROS1 rearrangement.	Crizotinib	13-23	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	87-91
27197808-0	2016	Crizotinib primary resistance overcome by ceritinib in a patient with ALK-rearranged non-small cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	70-73
27197808-2	2016	Although second-generation ALK inhibitors have shown activity in patients pretreated with crizotinib who experienced secondary resistance, this is the first report to date describing their efficacy in a case of primary resistance.	Crizotinib	90-100	ALK receptor tyrosine kinase	Homo sapiens	27-30
27662658-1	2016	ALK-positive Anaplastic Large Cell Lymphoma (ALCL) represents a subset of Non-Hodgkin Lymphoma whose treatment benefited from crizotinib development, a dual ALK/MET inhibitor.	Crizotinib	126-136	anaplastic lymphoma kinase	Mus musculus	0-3
27662658-1	2016	ALK-positive Anaplastic Large Cell Lymphoma (ALCL) represents a subset of Non-Hodgkin Lymphoma whose treatment benefited from crizotinib development, a dual ALK/MET inhibitor.	Crizotinib	126-136	anaplastic lymphoma kinase	Mus musculus	157-160
27662658-2	2016	Crizotinib blocks ALK-triggered pathways such as PI3K/AKT/mTOR, indispensable for survival of ALK-driven tumors.Despite the positive impact of targeted treatment in ALCL, resistant clones are often selected during therapy.	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	18-21
27662658-2	2016	Crizotinib blocks ALK-triggered pathways such as PI3K/AKT/mTOR, indispensable for survival of ALK-driven tumors.Despite the positive impact of targeted treatment in ALCL, resistant clones are often selected during therapy.	Crizotinib	0-10	thymoma viral proto-oncogene 1	Mus musculus	54-57
27662658-2	2016	Crizotinib blocks ALK-triggered pathways such as PI3K/AKT/mTOR, indispensable for survival of ALK-driven tumors.Despite the positive impact of targeted treatment in ALCL, resistant clones are often selected during therapy.	Crizotinib	0-10	mechanistic target of rapamycin kinase	Mus musculus	58-62
27662658-2	2016	Crizotinib blocks ALK-triggered pathways such as PI3K/AKT/mTOR, indispensable for survival of ALK-driven tumors.Despite the positive impact of targeted treatment in ALCL, resistant clones are often selected during therapy.	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	94-97
27742657-0	2016	Chromoplectic TPM3-ALK rearrangement in a patient with inflammatory myofibroblastic tumor who responded to ceritinib after progression on crizotinib.	Crizotinib	138-148	tropomyosin 3	Homo sapiens	14-18
27742657-0	2016	Chromoplectic TPM3-ALK rearrangement in a patient with inflammatory myofibroblastic tumor who responded to ceritinib after progression on crizotinib.	Crizotinib	138-148	ALK receptor tyrosine kinase	Homo sapiens	19-22
27987587-3	2016	Here, we describe a patient with a SQCC harboring ROS1 rearrangement and a response to the target therapy, crizotinib.	Crizotinib	107-117	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	50-54
27405684-2	2016	Patients with ALK-rearranged tumors who have developed disease progression during alectinib treatment will receive crizotinib monotherapy until disease progression or the occurrence of unacceptable toxicity.	Crizotinib	115-125	ALK receptor tyrosine kinase	Homo sapiens	14-17
27405684-7	2016	We will obtain information regarding whether crizotinib, which targets not only ALK, but also MET, can truly produce efficacy with acceptable safety profiles in ALK+ non-small-cell lung cancer even in the alectinib-refractory setting.	Crizotinib	45-55	ALK receptor tyrosine kinase	Homo sapiens	80-83
27405684-7	2016	We will obtain information regarding whether crizotinib, which targets not only ALK, but also MET, can truly produce efficacy with acceptable safety profiles in ALK+ non-small-cell lung cancer even in the alectinib-refractory setting.	Crizotinib	45-55	ALK receptor tyrosine kinase	Homo sapiens	161-164
27693947-2	2016	The marketed ROS-1 inhibitors such as Crizotinib suffer from the tribulations of growing resistance due to mutations primarily Gly2032Arg in the ROS-1 protein.	Crizotinib	38-48	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	13-18
27318655-0	2016	Progression-Free and Overall Survival of Patients With ALK Rearrangement-Positive Non-Small Cell Lung Cancer Treated Sequentially With Crizotinib and Alectinib.	Crizotinib	135-145	ALK receptor tyrosine kinase	Homo sapiens	55-58
27318655-2	2016	The effect on overall survival (OS) of sequential treatment with the first- and second-generation ALK-TKIs crizotinib and alectinib, respectively, has remained unknown.	Crizotinib	107-117	ALK receptor tyrosine kinase	Homo sapiens	98-101
27318655-4	2016	MATERIALS AND METHODS: Eleven patients with ALK-rearranged NSCLC treated with crizotinib followed by alectinib were identified.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	44-47
27341790-2	2016	Since the first description of the echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) rearrangement in 4% of cases of non-small-cell lung cancer in 2007, a highly potent and selective ALK inhibitor, crizotinib, was developed and approved in record time.	Crizotinib	235-245	ALK receptor tyrosine kinase	Homo sapiens	117-120
27341790-2	2016	Since the first description of the echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) rearrangement in 4% of cases of non-small-cell lung cancer in 2007, a highly potent and selective ALK inhibitor, crizotinib, was developed and approved in record time.	Crizotinib	235-245	ALK receptor tyrosine kinase	Homo sapiens	220-223
27341790-5	2016	These have led to the recognition of the role of secondary resistance mutations, of ALK amplification, and of activation of bypass signaling, all of which contribute to resistance to crizotinib.	Crizotinib	183-193	ALK receptor tyrosine kinase	Homo sapiens	84-87
27341790-6	2016	Moreover, the rapid preclinical and clinical development of multiple second-generation ALK inhibitors that exhibit significant clinical activity against crizotinib-resistant disease has provided multiple options to treating physicians, with the ultimate goal the delivery of tailored medicine.	Crizotinib	153-163	ALK receptor tyrosine kinase	Homo sapiens	87-90
27238948-0	2016	ALK-positive large B-cell lymphoma with strong CD30 expression; a diagnostic pitfall and resistance to brentuximab and crizotinib.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	0-3
27693947-2	2016	The marketed ROS-1 inhibitors such as Crizotinib suffer from the tribulations of growing resistance due to mutations primarily Gly2032Arg in the ROS-1 protein.	Crizotinib	38-48	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	145-150
27666124-0	2016	miR-200c regulates crizotinib-resistant ALK-positive lung cancer cells by reversing epithelial-mesenchymal transition via targeting ZEB1.	Crizotinib	19-29	microRNA 200c	Homo sapiens	0-8
27469327-11	2016	Our results are of potential clinical importance because crizotinib, a selective ALK inhibitor, has demonstrated effect in patients whose tumors harbor ALK rearrangements.	Crizotinib	57-67	ALK receptor tyrosine kinase	Homo sapiens	81-84
27469327-11	2016	Our results are of potential clinical importance because crizotinib, a selective ALK inhibitor, has demonstrated effect in patients whose tumors harbor ALK rearrangements.	Crizotinib	57-67	ALK receptor tyrosine kinase	Homo sapiens	152-155
27666124-0	2016	miR-200c regulates crizotinib-resistant ALK-positive lung cancer cells by reversing epithelial-mesenchymal transition via targeting ZEB1.	Crizotinib	19-29	ALK receptor tyrosine kinase	Homo sapiens	40-43
27666124-0	2016	miR-200c regulates crizotinib-resistant ALK-positive lung cancer cells by reversing epithelial-mesenchymal transition via targeting ZEB1.	Crizotinib	19-29	zinc finger E-box binding homeobox 1	Homo sapiens	132-136
27666124-1	2016	Crizotinib is an orally administered drug for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	77-103
27666124-1	2016	Crizotinib is an orally administered drug for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	105-108
27666124-2	2016	Despite the impressive efficacy of crizotinib in the treatment of ALK-positive lung cancer, acquired resistance eventually develops in the majority of patients.	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	66-69
27666124-3	2016	The microRNA (miR)-200c reverses the resistance of lung cancer cells to various chemotherapeutic drugs and molecular targeted drugs, however, whether it can reverse the resistance of crizotinib remains unknown.	Crizotinib	183-193	microRNA 200c	Homo sapiens	4-23
27666124-9	2016	In addition, EMT was reversed by miR-200c, which suggests that miR-200c may serve a role in mediating the sensitivity of NCI-2228/CRI cells to crizotinib.	Crizotinib	143-153	microRNA 200c	Homo sapiens	33-41
27666124-9	2016	In addition, EMT was reversed by miR-200c, which suggests that miR-200c may serve a role in mediating the sensitivity of NCI-2228/CRI cells to crizotinib.	Crizotinib	143-153	microRNA 200c	Homo sapiens	63-71
27666124-10	2016	The present study may therefore contribute to improving the sensitivity of ALK positive lung cancer cells to crizotinib.	Crizotinib	109-119	ALK receptor tyrosine kinase	Homo sapiens	75-78
27554841-8	2016	The prognosis remains uncertain but ALK rearrangement may be of potential value for target therapy with crizotinib.	Crizotinib	104-114	ALK receptor tyrosine kinase	Homo sapiens	36-39
27535289-2	2016	Crizotinib, a highly effective inhibitor of ROS1 kinase activity, is now FDA-approved for the treatment of patients with advanced ROS1-positive NSCLC.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	44-48
27017063-1	2016	BACKGROUND: EGFR tyrosine kinase inhibitors and crizotinib are nowadays the optimal treatment for metastatic lung cancer with activation of EGFR mutations and ALK rearrangement.	Crizotinib	48-58	epidermal growth factor receptor	Homo sapiens	140-144
27017063-1	2016	BACKGROUND: EGFR tyrosine kinase inhibitors and crizotinib are nowadays the optimal treatment for metastatic lung cancer with activation of EGFR mutations and ALK rearrangement.	Crizotinib	48-58	ALK receptor tyrosine kinase	Homo sapiens	159-162
27535289-2	2016	Crizotinib, a highly effective inhibitor of ROS1 kinase activity, is now FDA-approved for the treatment of patients with advanced ROS1-positive NSCLC.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	130-134
27797842-0	2016	Crizotinib in ROS1 rearranged non-small cell lung cancer (NSCLC), from response to resistance.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	14-18
27673365-6	2016	Analysis of H2228 tumours, which had relapsed on crizotinib monotherapy, identified a number of clinically relevant crizotinib resistance mechanisms, suggesting that HSP90 inhibitor treatment was capable of suppressing multiple mechanisms of resistance.	Crizotinib	116-126	heat shock protein 90 alpha family class A member 1	Homo sapiens	166-171
27797842-1	2016	We examined an immediate, but short-lived, response to crizotinib, a drug with a new indication for ROS1 rearranged non-small cell lung cancer (NSCLC) in a middle-aged non-smoker.	Crizotinib	55-65	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	100-104
27799783-2	2016	Despite the high efficacy of crizotinib, the first oral ALK TKI approved for the treatment of ALK-positive NSCLC, almost all patients inevitably develop acquired resistance, showing disease progression in the brain or in other parenchymal sites.	Crizotinib	29-39	ALK receptor tyrosine kinase	Homo sapiens	56-59
27811184-6	2016	Among these, knocking down fibroblast growth factor receptor substrate 2 (FRS2) or coiled-coil and C2 domain-containing protein 1A (CC2D1A), both scaffolding proteins, sensitized multiple ALK fusion cell lines to the ALK inhibitors crizotinib and alectinib.	Crizotinib	232-242	fibroblast growth factor receptor substrate 2	Homo sapiens	27-72
27811184-6	2016	Among these, knocking down fibroblast growth factor receptor substrate 2 (FRS2) or coiled-coil and C2 domain-containing protein 1A (CC2D1A), both scaffolding proteins, sensitized multiple ALK fusion cell lines to the ALK inhibitors crizotinib and alectinib.	Crizotinib	232-242	coiled-coil and C2 domain containing 1A	Homo sapiens	83-130
27811184-6	2016	Among these, knocking down fibroblast growth factor receptor substrate 2 (FRS2) or coiled-coil and C2 domain-containing protein 1A (CC2D1A), both scaffolding proteins, sensitized multiple ALK fusion cell lines to the ALK inhibitors crizotinib and alectinib.	Crizotinib	232-242	coiled-coil and C2 domain containing 1A	Homo sapiens	132-138
27799783-2	2016	Despite the high efficacy of crizotinib, the first oral ALK TKI approved for the treatment of ALK-positive NSCLC, almost all patients inevitably develop acquired resistance, showing disease progression in the brain or in other parenchymal sites.	Crizotinib	29-39	ALK receptor tyrosine kinase	Homo sapiens	94-97
27799783-3	2016	Second- or third-generation ALK TKIs have shown to be active in crizotinib-pretreated or crizotinib-naive ALK-positive patients, even in those with brain metastases.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	28-31
27799783-3	2016	Second- or third-generation ALK TKIs have shown to be active in crizotinib-pretreated or crizotinib-naive ALK-positive patients, even in those with brain metastases.	Crizotinib	89-99	ALK receptor tyrosine kinase	Homo sapiens	28-31
27799783-3	2016	Second- or third-generation ALK TKIs have shown to be active in crizotinib-pretreated or crizotinib-naive ALK-positive patients, even in those with brain metastases.	Crizotinib	89-99	ALK receptor tyrosine kinase	Homo sapiens	106-109
26990744-7	2016	Being positive for ALK rearrangement, the patient was treated with crizotinib with a good response.	Crizotinib	67-77	ALK receptor tyrosine kinase	Homo sapiens	19-22
27785052-3	2016	CASE PRESENTATION: We present a patient with recurrent ALK-rearranged NSCLC that developed multiple brain metastases and meningitis carcinomatosa after sequential treatment with several lines of cytotoxic chemotherapy, crizotinib, and alectinib.	Crizotinib	219-229	ALK receptor tyrosine kinase	Homo sapiens	55-58
27533086-7	2016	ORR of crizotinib was 40% (2/5) for EGFR/ALK co-altered and 73.9% (17/23) for ALK-rearranged (P= 0.29), with a median PFS of 1.9 and 6.9 months (hazard ratio [HR], 0.40; 95% [CI] 0.15-1.10, P = 0.08).	Crizotinib	7-17	epidermal growth factor receptor	Homo sapiens	36-40
27533086-7	2016	ORR of crizotinib was 40% (2/5) for EGFR/ALK co-altered and 73.9% (17/23) for ALK-rearranged (P= 0.29), with a median PFS of 1.9 and 6.9 months (hazard ratio [HR], 0.40; 95% [CI] 0.15-1.10, P = 0.08).	Crizotinib	7-17	ALK receptor tyrosine kinase	Homo sapiens	41-44
27611848-2	2016	The presence of ROS1 rearrangements defines a small subgroup of lung adenocarcinomas (~1-2%) with peculiar clinic-pathological characteristics and increased sensitivity to Crizotinib.	Crizotinib	172-182	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	16-20
26990744-0	2016	Crizotinib Response in a Late Relapse of ALK-positive Lung Adenocarcinoma.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	41-44
27432227-1	2016	Advanced, anaplastic lymphoma kinase (ALK)-positive lung cancer is currently treated with the first-generation ALK inhibitor crizotinib followed by more potent, second-generation ALK inhibitors (e.g., ceritinib and alectinib) upon progression.	Crizotinib	125-135	ALK receptor tyrosine kinase	Homo sapiens	10-36
27432227-1	2016	Advanced, anaplastic lymphoma kinase (ALK)-positive lung cancer is currently treated with the first-generation ALK inhibitor crizotinib followed by more potent, second-generation ALK inhibitors (e.g., ceritinib and alectinib) upon progression.	Crizotinib	125-135	ALK receptor tyrosine kinase	Homo sapiens	38-41
27432227-2	2016	Second-generation inhibitors are generally effective even in the absence of crizotinib-resistant ALK mutations, likely reflecting incomplete inhibition of ALK by crizotinib in many cases.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	97-100
27544536-1	2016	ROS1 gene-rearrangement in non-small-cell lung cancer (NSCLC) patients has recently been identified as a driver gene and benefited from crizotinib treatment.	Crizotinib	136-146	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	0-4
27468827-2	2016	In clinical practice, three small molecule inhibitors of ALK-1 are used, namely crizotinib, ceritinib and alectinib.	Crizotinib	80-90	activin A receptor like type 1	Homo sapiens	57-62
27468827-4	2016	Crizotinib is approved for the treatment of advanced ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	53-56
27354483-0	2016	Differential Crizotinib Response Duration Among ALK Fusion Variants in ALK-Positive Non-Small-Cell Lung Cancer.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	71-74
27354483-1	2016	PURPOSE: Anaplastic lymphoma kinase (ALK) rearrangement-positive non-small-cell lung cancers can be effectively treated with an ALK tyrosine kinase inhibitor (TKI) such as crizotinib, but the response magnitude and duration are heterogeneous.	Crizotinib	172-182	ALK receptor tyrosine kinase	Homo sapiens	9-35
27354483-1	2016	PURPOSE: Anaplastic lymphoma kinase (ALK) rearrangement-positive non-small-cell lung cancers can be effectively treated with an ALK tyrosine kinase inhibitor (TKI) such as crizotinib, but the response magnitude and duration are heterogeneous.	Crizotinib	172-182	ALK receptor tyrosine kinase	Homo sapiens	37-40
27354483-2	2016	Several ALK variants have been identified, but few studies have focused on the effects of different ALK variants on the efficacy of crizotinib.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	100-103
27354483-3	2016	PATIENTS AND METHODS: Among 55 patients treated with crizotinib as the initial ALK-TKI between January 2007 and December 2014, we identified 35 patients with tumor specimens that could be evaluated for ALK variants by reverse transcription polymerase chain reaction.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	79-82
27354483-3	2016	PATIENTS AND METHODS: Among 55 patients treated with crizotinib as the initial ALK-TKI between January 2007 and December 2014, we identified 35 patients with tumor specimens that could be evaluated for ALK variants by reverse transcription polymerase chain reaction.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	202-205
27354483-4	2016	We retrospectively evaluated the efficacy of crizotinib on the basis of the objective response rate and progression-free survival (PFS) according to the ALK variants.	Crizotinib	45-55	ALK receptor tyrosine kinase	Homo sapiens	153-156
27354483-9	2016	CONCLUSION: Our results indicate the better efficacy of crizotinib in patients with ALK variant 1 versus non-variant 1.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	84-87
27458283-0	2016	Differential Sensitivity to Crizotinib: Does EML4-ALK Fusion Variant Matter?	Crizotinib	28-38	EMAP like 4	Homo sapiens	45-49
27458283-0	2016	Differential Sensitivity to Crizotinib: Does EML4-ALK Fusion Variant Matter?	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	50-53
27663401-0	2016	A Case of Lung Adenocarcinoma Resistant to Crizotinib Harboring a Novel EML4-ALK Variant, Exon 6 of EML4 Fused to Exon 18 of ALK.	Crizotinib	43-53	EMAP like 4	Homo sapiens	72-76
27663401-0	2016	A Case of Lung Adenocarcinoma Resistant to Crizotinib Harboring a Novel EML4-ALK Variant, Exon 6 of EML4 Fused to Exon 18 of ALK.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	77-80
27663401-0	2016	A Case of Lung Adenocarcinoma Resistant to Crizotinib Harboring a Novel EML4-ALK Variant, Exon 6 of EML4 Fused to Exon 18 of ALK.	Crizotinib	43-53	EMAP like 4	Homo sapiens	100-104
27663401-0	2016	A Case of Lung Adenocarcinoma Resistant to Crizotinib Harboring a Novel EML4-ALK Variant, Exon 6 of EML4 Fused to Exon 18 of ALK.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	125-128
27867635-0	2016	Efficacy of crizotinib in ALK fusion variants.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	26-29
27699584-2	2016	The drug is approved in several countries worldwide for the treatment of patients with ALK-positive, advanced NSCLC who have previously received the first-generation ALK inhibitor crizotinib (indication details may vary by country).	Crizotinib	180-190	ALK receptor tyrosine kinase	Homo sapiens	87-90
27699584-2	2016	The drug is approved in several countries worldwide for the treatment of patients with ALK-positive, advanced NSCLC who have previously received the first-generation ALK inhibitor crizotinib (indication details may vary by country).	Crizotinib	180-190	ALK receptor tyrosine kinase	Homo sapiens	166-169
27418132-0	2016	Responses to crizotinib in patients with ALK-positive lung adenocarcinoma who tested immunohistochemistry (IHC)-positive and fluorescence in situ hybridization (FISH)-negative.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	41-44
27418132-2	2016	We evaluated 6 ALK-positive lung adenocarcinoma patients who tested Ventana IHC-positive and FISH-negative and assessed their clinical responses to the ALK tyrosine kinase inhibitor (TKI) crizotinib.	Crizotinib	188-198	ALK receptor tyrosine kinase	Homo sapiens	15-18
27418132-8	2016	These findings indicate that patients with ALK-positive lung adenocarcinoma who test Ventana IHC-positive and FISH-negative may still respond to crizotinib therapy.	Crizotinib	145-155	ALK receptor tyrosine kinase	Homo sapiens	43-46
26990744-8	2016	To the best of our knowledge, it is the first case of a late relapse of ALK-positive lung adenocarcinoma sensitive to crizotinib in the literature.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	72-75
27637025-13	2016	CONCLUSION: A majority of our ALK positive NSCLC patients were exposed to Crizotinib through the help of various support mechanisms and these patients had similar outcomes to that reported from previously published literature.	Crizotinib	74-84	ALK receptor tyrosine kinase	Homo sapiens	30-33
27641368-0	2016	The use of cellular thermal shift assay (CETSA) to study Crizotinib resistance in ALK-expressing human cancers.	Crizotinib	57-67	ALK receptor tyrosine kinase	Homo sapiens	82-85
27641368-2	2016	While Crizotinib, an ALK inhibitor, has been found to be therapeutically useful against a subset of ALK(+) tumours, clinical resistance to this drug has been well recognized and the mechanism of this phenomenon is incompletely understood.	Crizotinib	6-16	ALK receptor tyrosine kinase	Homo sapiens	21-24
27641368-2	2016	While Crizotinib, an ALK inhibitor, has been found to be therapeutically useful against a subset of ALK(+) tumours, clinical resistance to this drug has been well recognized and the mechanism of this phenomenon is incompletely understood.	Crizotinib	6-16	ALK receptor tyrosine kinase	Homo sapiens	100-103
27641368-3	2016	Using the cellular thermal shift assay (CETSA), we measured the Crizotinib-ALK binding in a panel of ALK(+) cell lines, and correlated the findings with the ALK structure and its interactions with specific binding proteins.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	75-78
27641368-3	2016	Using the cellular thermal shift assay (CETSA), we measured the Crizotinib-ALK binding in a panel of ALK(+) cell lines, and correlated the findings with the ALK structure and its interactions with specific binding proteins.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	101-104
27641368-3	2016	Using the cellular thermal shift assay (CETSA), we measured the Crizotinib-ALK binding in a panel of ALK(+) cell lines, and correlated the findings with the ALK structure and its interactions with specific binding proteins.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	101-104
27641368-4	2016	The Crizotinib IC50 significantly correlated with Crizotinib-ALK binding.	Crizotinib	4-14	ALK receptor tyrosine kinase	Homo sapiens	61-64
27641368-4	2016	The Crizotinib IC50 significantly correlated with Crizotinib-ALK binding.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	61-64
27641368-5	2016	The suboptimal Crizotinib-ALK binding in Crizotinib-resistant cells is not due to the cell-specific environment, since transfection of NPM-ALK into these cells revealed substantial Crizotinib-NPM-ALK binding.	Crizotinib	15-25	ALK receptor tyrosine kinase	Homo sapiens	26-29
27641368-5	2016	The suboptimal Crizotinib-ALK binding in Crizotinib-resistant cells is not due to the cell-specific environment, since transfection of NPM-ALK into these cells revealed substantial Crizotinib-NPM-ALK binding.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	26-29
27641368-5	2016	The suboptimal Crizotinib-ALK binding in Crizotinib-resistant cells is not due to the cell-specific environment, since transfection of NPM-ALK into these cells revealed substantial Crizotinib-NPM-ALK binding.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	139-142
27641368-5	2016	The suboptimal Crizotinib-ALK binding in Crizotinib-resistant cells is not due to the cell-specific environment, since transfection of NPM-ALK into these cells revealed substantial Crizotinib-NPM-ALK binding.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	139-142
27641368-5	2016	The suboptimal Crizotinib-ALK binding in Crizotinib-resistant cells is not due to the cell-specific environment, since transfection of NPM-ALK into these cells revealed substantial Crizotinib-NPM-ALK binding.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	26-29
27641368-5	2016	The suboptimal Crizotinib-ALK binding in Crizotinib-resistant cells is not due to the cell-specific environment, since transfection of NPM-ALK into these cells revealed substantial Crizotinib-NPM-ALK binding.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	139-142
27641368-5	2016	The suboptimal Crizotinib-ALK binding in Crizotinib-resistant cells is not due to the cell-specific environment, since transfection of NPM-ALK into these cells revealed substantial Crizotinib-NPM-ALK binding.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	139-142
27641368-6	2016	Interestingly, we found that the resistant cells expressed higher protein level of beta-catenin and siRNA knockdown restored Crizotinib-ALK binding (correlated with a significant lowering of IC50).	Crizotinib	125-135	catenin beta 1	Homo sapiens	83-95
27641368-6	2016	Interestingly, we found that the resistant cells expressed higher protein level of beta-catenin and siRNA knockdown restored Crizotinib-ALK binding (correlated with a significant lowering of IC50).	Crizotinib	125-135	ALK receptor tyrosine kinase	Homo sapiens	136-139
27641368-7	2016	Computational analysis of the crystal structures suggests that beta-catenin exerts steric hindrance to the Crizotinib-ALK binding.	Crizotinib	107-117	catenin beta 1	Homo sapiens	63-75
27641368-7	2016	Computational analysis of the crystal structures suggests that beta-catenin exerts steric hindrance to the Crizotinib-ALK binding.	Crizotinib	107-117	ALK receptor tyrosine kinase	Homo sapiens	118-121
27641368-8	2016	In conclusion, the Crizotinib-ALK binding measurable by CETSA is useful in predicting Crizotinib sensitivity, and Crizotinib-ALK binding is in turn dictated by the structure of ALK and some of its binding partners.	Crizotinib	19-29	ALK receptor tyrosine kinase	Homo sapiens	30-33
27641368-8	2016	In conclusion, the Crizotinib-ALK binding measurable by CETSA is useful in predicting Crizotinib sensitivity, and Crizotinib-ALK binding is in turn dictated by the structure of ALK and some of its binding partners.	Crizotinib	86-96	ALK receptor tyrosine kinase	Homo sapiens	30-33
27641368-8	2016	In conclusion, the Crizotinib-ALK binding measurable by CETSA is useful in predicting Crizotinib sensitivity, and Crizotinib-ALK binding is in turn dictated by the structure of ALK and some of its binding partners.	Crizotinib	86-96	ALK receptor tyrosine kinase	Homo sapiens	30-33
27623107-3	2016	Here, we studied the combinatorial therapeutic efficacy of the MET/ALK inhibitor crizotinib, with either a pan-class I PI3K inhibitor, BKM120, or with a PI3K/mTOR dual inhibitor, GDC-0980, in mesothelioma.	Crizotinib	81-91	anaplastic lymphoma kinase	Mus musculus	67-70
27623107-7	2016	Both crizotinib and BKM120 strongly inhibited the activity of MET and PI3K as evidenced by the decreased phosphorylation of MET, AKT and ribosomal S6 kinase.	Crizotinib	5-15	thymoma viral proto-oncogene 1	Mus musculus	129-132
26712101-7	2016	Twelve patients with an EML4-ALK translocation received crizotinib and 7 of these had disease progression within 3 months (2 had a concomitant KRAS mutation and 1 had a concomitant EGFR mutation).	Crizotinib	56-66	EMAP like 4	Homo sapiens	24-28
27573754-2	2016	The discovery of ALK gene rearrangements in a subset of NSCLC specimens and the identification and development of the first-in-class ALK inhibitor crizotinib provided a personalised treatment option for patients with advanced ALK-positive NSCLC.	Crizotinib	147-157	ALK receptor tyrosine kinase	Homo sapiens	133-136
27573754-2	2016	The discovery of ALK gene rearrangements in a subset of NSCLC specimens and the identification and development of the first-in-class ALK inhibitor crizotinib provided a personalised treatment option for patients with advanced ALK-positive NSCLC.	Crizotinib	147-157	ALK receptor tyrosine kinase	Homo sapiens	133-136
27573754-3	2016	Crizotinib demonstrated rapid and durable responses in advanced ALK-positive NSCLC patients in phase I and II studies, leading to accelerated FDA approval.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	64-67
27573754-6	2016	Overall, crizotinib has been shown to provide a valuable first- and second-line treatment option and is now the first-line standard of care for patients with advanced ALK-positive NSCLC.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	167-170
27573755-8	2016	Two ALK tyrosine kinase inhibitors (TKIs), crizotinib and ceritinib, are currently approved in Europe for use in ALK-positive NSCLC and several others are in development.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	4-7
27573755-8	2016	Two ALK tyrosine kinase inhibitors (TKIs), crizotinib and ceritinib, are currently approved in Europe for use in ALK-positive NSCLC and several others are in development.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	113-116
27573756-3	2016	Fortuitously, crizotinib, a small molecule tyrosine kinase inhibitor initially developed to target cMET, was able to be repurposed for ALK-rearranged (ALK+) NSCLC.	Crizotinib	14-24	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	99-103
27573756-3	2016	Fortuitously, crizotinib, a small molecule tyrosine kinase inhibitor initially developed to target cMET, was able to be repurposed for ALK-rearranged (ALK+) NSCLC.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	135-138
27573756-3	2016	Fortuitously, crizotinib, a small molecule tyrosine kinase inhibitor initially developed to target cMET, was able to be repurposed for ALK-rearranged (ALK+) NSCLC.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	151-154
27325282-4	2016	Based on tumor genotyping and functional in vitro data, the patient was treated with the dual ALK-MET inhibitor crizotinib plus vemurafenib, thus switching to dual MET and BRAF blockade, with rapid and marked effectiveness of such strategy.	Crizotinib	112-122	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	172-176
27130468-7	2016	In our review of the literature and taken together with our patients, 25 of the 88 (28%) patients with crizotinib failure had secondary ALK mutation; L1196M mutation was most common (n = 11).	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	136-139
27130468-8	2016	Patients with secondary ALK mutation other than L1196M had a longer progression-free survival after crizotinib than patients with L1196M (median, 12.0 vs. 7.0 months; P = .04).	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	24-27
27565908-1	2016	INTRODUCTION: Anaplastic lymphoma kinase (ALK) rearranged lung adenocarcinomas are responsive to the multitargeted ALK inhibitor crizotinib.	Crizotinib	129-139	ALK receptor tyrosine kinase	Homo sapiens	14-40
27483357-1	2016	The first-in-class inhibitor of ALK, c-MET and ROS1, crizotinib (Xalkori), has shown remarkable clinical efficacy in treatment of ALK-positive non-small cell lung cancer.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	32-35
27483357-1	2016	The first-in-class inhibitor of ALK, c-MET and ROS1, crizotinib (Xalkori), has shown remarkable clinical efficacy in treatment of ALK-positive non-small cell lung cancer.	Crizotinib	53-63	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	47-51
27483357-1	2016	The first-in-class inhibitor of ALK, c-MET and ROS1, crizotinib (Xalkori), has shown remarkable clinical efficacy in treatment of ALK-positive non-small cell lung cancer.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	130-133
27483357-2	2016	However, in neuroblastoma, activating mutations in the ALK kinase domain are typically refractory to crizotinib treatment, highlighting the need for more potent inhibitors.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	55-58
27288979-1	2016	INTRODUCTION: Crizotinib and ceritinib have been developed to treat advanced or metastatic NSCLC by inhibiting anaplastic lymphoma receptor tyrosine kinase gene (ALK).	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	162-165
27565908-1	2016	INTRODUCTION: Anaplastic lymphoma kinase (ALK) rearranged lung adenocarcinomas are responsive to the multitargeted ALK inhibitor crizotinib.	Crizotinib	129-139	ALK receptor tyrosine kinase	Homo sapiens	42-45
27565908-1	2016	INTRODUCTION: Anaplastic lymphoma kinase (ALK) rearranged lung adenocarcinomas are responsive to the multitargeted ALK inhibitor crizotinib.	Crizotinib	129-139	ALK receptor tyrosine kinase	Homo sapiens	115-118
27565908-2	2016	One of the common mechanisms of resistance to crizotinib is the acquisition of ALK kinase domain mutations.	Crizotinib	46-56	ALK receptor tyrosine kinase	Homo sapiens	79-82
27565908-3	2016	However, the presence of ALK mutations in crizotinib-naive tumors has not been widely reported and it is unclear if de novo ALK mutations affect the response to crizotinib.	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	25-28
27565908-5	2016	RESULTS: ALK rearranged cell lines with ALK kinase domain mutations were heterogeneously less inhibited by increasing concentrations of crizotinib than cells driven solely by EML4-ALK fusions.	Crizotinib	136-146	ALK receptor tyrosine kinase	Homo sapiens	9-12
27565908-5	2016	RESULTS: ALK rearranged cell lines with ALK kinase domain mutations were heterogeneously less inhibited by increasing concentrations of crizotinib than cells driven solely by EML4-ALK fusions.	Crizotinib	136-146	ALK receptor tyrosine kinase	Homo sapiens	40-43
27565908-5	2016	RESULTS: ALK rearranged cell lines with ALK kinase domain mutations were heterogeneously less inhibited by increasing concentrations of crizotinib than cells driven solely by EML4-ALK fusions.	Crizotinib	136-146	ALK receptor tyrosine kinase	Homo sapiens	40-43
27565908-7	2016	We identified one TKI-naive ALK rearranged tumor with an ALK kinase domain mutation: ALK-S1206F (mutations at ALK-S1206 shifted crizotinib inhibitory curves only minimally in preclinical models).	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	28-31
27565908-7	2016	We identified one TKI-naive ALK rearranged tumor with an ALK kinase domain mutation: ALK-S1206F (mutations at ALK-S1206 shifted crizotinib inhibitory curves only minimally in preclinical models).	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	57-60
27565908-7	2016	We identified one TKI-naive ALK rearranged tumor with an ALK kinase domain mutation: ALK-S1206F (mutations at ALK-S1206 shifted crizotinib inhibitory curves only minimally in preclinical models).	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	57-60
27747151-6	2016	Crizotinib and alectinib showed marked decrease of serum CEA value from 731.9 to 122.2 and moderate radiologic response.	Crizotinib	0-10	CEA cell adhesion molecule 3	Homo sapiens	57-60
27565908-7	2016	We identified one TKI-naive ALK rearranged tumor with an ALK kinase domain mutation: ALK-S1206F (mutations at ALK-S1206 shifted crizotinib inhibitory curves only minimally in preclinical models).	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	57-60
27565908-8	2016	The never smoker whose tumor harbored de novo EML4-ALK-E5;A20+ALK-S1206F only achieved a 4-month radiographic response to crizotinib 250mg twice daily.	Crizotinib	122-132	EMAP like 4	Homo sapiens	46-50
27565908-8	2016	The never smoker whose tumor harbored de novo EML4-ALK-E5;A20+ALK-S1206F only achieved a 4-month radiographic response to crizotinib 250mg twice daily.	Crizotinib	122-132	ALK receptor tyrosine kinase	Homo sapiens	62-65
27565911-3	2016	We report the case of a patient with ALK-rearranged NSCLC who presented acquired resistance to crizotinib and then alectinib.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	37-40
27363027-0	2016	Crizotinib inhibits NF2-associated schwannoma through inhibition of focal adhesion kinase 1.	Crizotinib	0-10	NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor	Homo sapiens	20-23
26829053-9	2016	Moreover, we found that crizotinib, an ALK inhibitor, almost completely inhibited the growth of ALK(R1275Q)/MYCN tumors in an allograft model.	Crizotinib	24-34	anaplastic lymphoma kinase	Mus musculus	39-42
26829053-9	2016	Moreover, we found that crizotinib, an ALK inhibitor, almost completely inhibited the growth of ALK(R1275Q)/MYCN tumors in an allograft model.	Crizotinib	24-34	anaplastic lymphoma kinase	Mus musculus	96-99
26829053-10	2016	Our findings provided insights into the cooperative mechanism of the mutated ALK and overexpressed MYCN in the pathogenesis of NB and demonstrated the effectiveness of crizotinib on ALK(R1275Q)-positive tumors.	Crizotinib	168-178	anaplastic lymphoma kinase	Mus musculus	182-185
27363027-6	2016	Subsequent studies confirm that inhibition of FAK1 is sufficient to suppress tumorigenesis in animal models of NF2 and that crizotinib-resistant forms of FAK1 can rescue the effects of treatment.	Crizotinib	124-134	protein tyrosine kinase 2	Homo sapiens	154-158
27363027-0	2016	Crizotinib inhibits NF2-associated schwannoma through inhibition of focal adhesion kinase 1.	Crizotinib	0-10	protein tyrosine kinase 2	Homo sapiens	68-91
27363027-4	2016	We identified crizotinib, a MET and ALK inhibitor, as a potent inhibitor of NF2-null Schwann cell proliferation in vitro and tumor growth in vivo.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	36-39
27363027-4	2016	We identified crizotinib, a MET and ALK inhibitor, as a potent inhibitor of NF2-null Schwann cell proliferation in vitro and tumor growth in vivo.	Crizotinib	14-24	NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor	Homo sapiens	76-79
27363027-5	2016	To identify the target/s of crizotnib we employed activity-based protein profiling (ABPP), leading to identification of FAK1 (PTK2) as the relevant target of crizotinib inhibition in NF2-null schwannoma cells.	Crizotinib	158-168	protein tyrosine kinase 2	Homo sapiens	120-124
27363027-5	2016	To identify the target/s of crizotnib we employed activity-based protein profiling (ABPP), leading to identification of FAK1 (PTK2) as the relevant target of crizotinib inhibition in NF2-null schwannoma cells.	Crizotinib	158-168	protein tyrosine kinase 2	Homo sapiens	126-130
27363027-5	2016	To identify the target/s of crizotnib we employed activity-based protein profiling (ABPP), leading to identification of FAK1 (PTK2) as the relevant target of crizotinib inhibition in NF2-null schwannoma cells.	Crizotinib	158-168	NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor	Homo sapiens	183-186
27561802-6	2016	Then crizotinib (250 mg, bid) was chosen for the existence of ROS1 fusion gene.	Crizotinib	5-15	BH3 interacting domain death agonist	Homo sapiens	25-28
27022118-0	2016	Intracranial Efficacy of Crizotinib Versus Chemotherapy in Patients With Advanced ALK-Positive Non-Small-Cell Lung Cancer: Results From PROFILE 1014.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	82-85
27561801-8	2016	CONCLUSIONS: First-line crizotinib therapy combined with local brain treatment can improve intracranial PFS for ALK-positive NSCLC with brain metastases.	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	112-115
27561802-2	2016	Crizotinib had been confirmed to be used in ROS1 (C-ros oncogene 1 receptor tyrosine kinase) rearranged lung adenocarcinoma, but its efficacy in lung cancer with brain metastasis was poor due to the blood brain barrier.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	44-48
27561802-2	2016	Crizotinib had been confirmed to be used in ROS1 (C-ros oncogene 1 receptor tyrosine kinase) rearranged lung adenocarcinoma, but its efficacy in lung cancer with brain metastasis was poor due to the blood brain barrier.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	50-91
27561802-3	2016	In the present study, we reported one case of ROS1 fusion lung adenocarcinoma with symptomatic brain matastasis, who was treated with brain metastases resection, crizotinib, and whole brain radiotherapy plus boost to residual brain metastasis.	Crizotinib	162-172	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	46-50
27766783-1	2016	Identification of the anaplastic lymphoma kinase (ALK) gene has refined the classification of non-small cell lung cancer (NSCLC) and promoted research on molecularly targeted drugs such as crizotinib, an ALK inhibitor with good efficacy, in ALK-rearranged NSCLC.	Crizotinib	189-199	ALK receptor tyrosine kinase	Homo sapiens	22-48
27766783-1	2016	Identification of the anaplastic lymphoma kinase (ALK) gene has refined the classification of non-small cell lung cancer (NSCLC) and promoted research on molecularly targeted drugs such as crizotinib, an ALK inhibitor with good efficacy, in ALK-rearranged NSCLC.	Crizotinib	189-199	ALK receptor tyrosine kinase	Homo sapiens	50-53
27766783-1	2016	Identification of the anaplastic lymphoma kinase (ALK) gene has refined the classification of non-small cell lung cancer (NSCLC) and promoted research on molecularly targeted drugs such as crizotinib, an ALK inhibitor with good efficacy, in ALK-rearranged NSCLC.	Crizotinib	189-199	ALK receptor tyrosine kinase	Homo sapiens	204-207
27766783-1	2016	Identification of the anaplastic lymphoma kinase (ALK) gene has refined the classification of non-small cell lung cancer (NSCLC) and promoted research on molecularly targeted drugs such as crizotinib, an ALK inhibitor with good efficacy, in ALK-rearranged NSCLC.	Crizotinib	189-199	ALK receptor tyrosine kinase	Homo sapiens	204-207
27766783-2	2016	At present, few studies have reported the efficacy of crizotinib in patients with ALK-rearranged NSCLC with brain metastases.	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	82-85
27766783-3	2016	In a patient with NSCLC harboring ALK-rearrangement who had brain metastases and poor performance status (PS), we obtained a durable response with crizotinib administered following multi-line chemotherapy regimens.	Crizotinib	147-157	ALK receptor tyrosine kinase	Homo sapiens	34-37
27561802-6	2016	Then crizotinib (250 mg, bid) was chosen for the existence of ROS1 fusion gene.	Crizotinib	5-15	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	62-66
27561802-11	2016	CONCLUSIONS: Crizotinib combined with palliative operation and radiation therapy (WBRT plus boost to residual brain metastasis) in the treatment of ROS1 fusion gene positive lung adenocarcinoma with symptomatic brain metastases, can effectively control intracranial lesions with good tolerance.	Crizotinib	13-23	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	148-152
27496196-0	2016	Lung adenocarcinoma harboring concomitant SPTBN1-ALK fusion, c-Met overexpression, and HER-2 amplification with inherent resistance to crizotinib, chemotherapy, and radiotherapy.	Crizotinib	135-145	erb-b2 receptor tyrosine kinase 2	Homo sapiens	87-92
27496196-1	2016	Crizotinib is a multi-targeted tyrosine kinase inhibitor (TKI) with activity against mesenchymal-epithelial transition factor (MET) and anaplastic lymphoma kinase (ALK).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	136-162
27496196-1	2016	Crizotinib is a multi-targeted tyrosine kinase inhibitor (TKI) with activity against mesenchymal-epithelial transition factor (MET) and anaplastic lymphoma kinase (ALK).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	164-167
27496196-3	2016	Herein, we present a 69-year-old never-smoker Chinese male with advanced lung adenocarcinoma harboring concomitant spectrin beta non-erythrocytic 1 (SPTBN1)-ALK fusion, c-Met overexpression, and human epidermal growth factor receptor-2 (HER-2) amplification with inherent resistance to crizotinib, chemotherapy, and radiotherapy.	Crizotinib	286-296	spectrin beta, non-erythrocytic 1	Homo sapiens	115-147
27496196-3	2016	Herein, we present a 69-year-old never-smoker Chinese male with advanced lung adenocarcinoma harboring concomitant spectrin beta non-erythrocytic 1 (SPTBN1)-ALK fusion, c-Met overexpression, and human epidermal growth factor receptor-2 (HER-2) amplification with inherent resistance to crizotinib, chemotherapy, and radiotherapy.	Crizotinib	286-296	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	169-174
27496196-5	2016	Therefore, c-Met overexpression, HER-2 gene amplification, and SPTBN1-ALK gene fusion can coexist in lung adenocarcinoma and may become a potential biomarker of cancer refractory to crizotinib, chemotherapy, and radiotherapy as well as of a relatively poor prognosis.	Crizotinib	182-192	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	11-16
27496196-5	2016	Therefore, c-Met overexpression, HER-2 gene amplification, and SPTBN1-ALK gene fusion can coexist in lung adenocarcinoma and may become a potential biomarker of cancer refractory to crizotinib, chemotherapy, and radiotherapy as well as of a relatively poor prognosis.	Crizotinib	182-192	spectrin beta, non-erythrocytic 1	Homo sapiens	63-69
27270784-0	2016	Pharmacokinetic profiles of significant adverse events with crizotinib in Japanese patients with ABCB1 polymorphism.	Crizotinib	60-70	ATP binding cassette subfamily B member 1	Homo sapiens	97-102
27480287-0	2016	Post-crizotinib management of effective ceritinib therapy in a patient with ALK-positive non-small cell lung cancer.	Crizotinib	5-15	ALK receptor tyrosine kinase	Homo sapiens	76-79
27480287-1	2016	BACKGROUND: We report the re-biopsied diagnosis of a patient with anaplastic lymphoma receptor tyrosine kinase (ALK)-positive lung adenocarcinoma successfully treated with ceritinib 450 mg/day taken with food following disease progression and gastrointestinal intolerance to crizotinib.	Crizotinib	275-285	ALK receptor tyrosine kinase	Homo sapiens	112-115
27270784-1	2016	Crizotinib is a standard treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	48-51
27232673-2	2016	Despite the initial response, after a median of 1-2 years, ALK-positive patients developed an acquired resistance to the ALK-inhibitor crizotinib.	Crizotinib	135-145	ALK receptor tyrosine kinase	Homo sapiens	59-62
27232673-2	2016	Despite the initial response, after a median of 1-2 years, ALK-positive patients developed an acquired resistance to the ALK-inhibitor crizotinib.	Crizotinib	135-145	ALK receptor tyrosine kinase	Homo sapiens	121-124
27068398-0	2016	An Activating KIT Mutation Induces Crizotinib Resistance in ROS1-Positive Lung Cancer.	Crizotinib	35-45	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	14-17
27359268-0	2016	Efficacy of crizotinib in first-line treatment of adults with ALK-positive advanced NSCLC.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	62-65
27359268-2	2016	Anaplastic lymphoma kinase (ALK) rearrangement characterizes a molecular subset of NSCLC with an impressive response to crizotinib.	Crizotinib	120-130	ALK receptor tyrosine kinase	Homo sapiens	0-26
27359268-2	2016	Anaplastic lymphoma kinase (ALK) rearrangement characterizes a molecular subset of NSCLC with an impressive response to crizotinib.	Crizotinib	120-130	ALK receptor tyrosine kinase	Homo sapiens	28-31
27359268-4	2016	EXPERT OPINION: To date, crizotinib should be established as a standard of care in previously untreated advanced NSCLC with ALK-rearrangement.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	124-127
27359268-6	2016	Second generation ALK inhibitors have demonstrated clinical activity in both crizotinib-refractory and crizotinib naive setting.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	18-21
27359268-6	2016	Second generation ALK inhibitors have demonstrated clinical activity in both crizotinib-refractory and crizotinib naive setting.	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	18-21
27068398-1	2016	INTRODUCTION: Patients with non-small cell lung cancer (NSCLC) harboring ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1) chromosomal rearrangements benefit from treatment with the ROS1 inhibitor crizotinib.	Crizotinib	206-216	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	73-119
27068398-1	2016	INTRODUCTION: Patients with non-small cell lung cancer (NSCLC) harboring ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1) chromosomal rearrangements benefit from treatment with the ROS1 inhibitor crizotinib.	Crizotinib	206-216	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	126-130
27068398-1	2016	INTRODUCTION: Patients with non-small cell lung cancer (NSCLC) harboring ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1) chromosomal rearrangements benefit from treatment with the ROS1 inhibitor crizotinib.	Crizotinib	206-216	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	191-195
27068398-4	2016	METHODS: An activating mutation in the KIT proto-oncogene receptor tyrosine kinase (KIT) (p.D816G) was identified by SNaPshot sequencing in a tumor sample from a patient with ROS1-positive NSCLC identified by fluorescence in situ hybridization whose disease progressed after initial response to crizotinib.	Crizotinib	295-305	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	39-82
27068398-4	2016	METHODS: An activating mutation in the KIT proto-oncogene receptor tyrosine kinase (KIT) (p.D816G) was identified by SNaPshot sequencing in a tumor sample from a patient with ROS1-positive NSCLC identified by fluorescence in situ hybridization whose disease progressed after initial response to crizotinib.	Crizotinib	295-305	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	39-42
27068398-4	2016	METHODS: An activating mutation in the KIT proto-oncogene receptor tyrosine kinase (KIT) (p.D816G) was identified by SNaPshot sequencing in a tumor sample from a patient with ROS1-positive NSCLC identified by fluorescence in situ hybridization whose disease progressed after initial response to crizotinib.	Crizotinib	295-305	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	175-179
27068398-8	2016	Expression of the KIT(D816G) rendered the HCC78 and CUTO2 cell lines resistant to crizotinib, and only dual inhibition of ROS1 and KIT with crizotinib and ponatinib could resensitize the cells to inhibition of proliferation.	Crizotinib	82-92	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	18-23
27068398-8	2016	Expression of the KIT(D816G) rendered the HCC78 and CUTO2 cell lines resistant to crizotinib, and only dual inhibition of ROS1 and KIT with crizotinib and ponatinib could resensitize the cells to inhibition of proliferation.	Crizotinib	82-92	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	18-21
27068398-8	2016	Expression of the KIT(D816G) rendered the HCC78 and CUTO2 cell lines resistant to crizotinib, and only dual inhibition of ROS1 and KIT with crizotinib and ponatinib could resensitize the cells to inhibition of proliferation.	Crizotinib	140-150	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	122-126
27068398-8	2016	Expression of the KIT(D816G) rendered the HCC78 and CUTO2 cell lines resistant to crizotinib, and only dual inhibition of ROS1 and KIT with crizotinib and ponatinib could resensitize the cells to inhibition of proliferation.	Crizotinib	140-150	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	18-21
27068398-10	2016	CONCLUSIONS: Activation of KIT by a gain-of-function somatic mutation is a novel mechanism of resistance to crizotinib in ROS1-rearranged NSCLC.	Crizotinib	108-118	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	27-30
27068398-10	2016	CONCLUSIONS: Activation of KIT by a gain-of-function somatic mutation is a novel mechanism of resistance to crizotinib in ROS1-rearranged NSCLC.	Crizotinib	108-118	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	122-126
27328934-0	2016	Benefit-Risk Summary of Crizotinib for the Treatment of Patients With ROS1 Alteration-Positive, Metastatic Non-Small Cell Lung Cancer.	Crizotinib	24-34	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	70-74
27393500-0	2016	Characteristics, treatment patterns, and survival among ALK+ non-small cell lung cancer (NSCLC) patients treated with crizotinib: A chart review study.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	56-59
27393500-1	2016	OBJECTIVES: Second-generation ALK inhibitors are recently available for ALK+ non-small cell lung cancer (NSCLC) patients previously treated with crizotinib.	Crizotinib	145-155	ALK receptor tyrosine kinase	Homo sapiens	30-33
27393500-1	2016	OBJECTIVES: Second-generation ALK inhibitors are recently available for ALK+ non-small cell lung cancer (NSCLC) patients previously treated with crizotinib.	Crizotinib	145-155	ALK receptor tyrosine kinase	Homo sapiens	72-75
27393500-2	2016	This study described characteristics, treatment sequencing, and outcomes among locally advanced/metastatic crizotinib-experienced ALK+ NSCLC patients.	Crizotinib	107-117	ALK receptor tyrosine kinase	Homo sapiens	130-133
27393500-4	2016	Participating clinicians identified their ALK+ NSCLC patients who received crizotinib and reported on their clinical characteristics, treatments, and survival using a pre-defined case report form.	Crizotinib	75-85	ALK receptor tyrosine kinase	Homo sapiens	42-45
27393500-6	2016	RESULTS: Participating clinicians reviewed charts of 158 ALK+ NSCLC patients treated with crizotinib during the study period.	Crizotinib	90-100	ALK receptor tyrosine kinase	Homo sapiens	57-60
27393517-0	2016	Effectiveness of crizotinib in a patient with ALK IHC-positive/FISH-negative metastatic lung adenocarcinoma.	Crizotinib	17-27	ALK receptor tyrosine kinase	Homo sapiens	46-49
27393517-1	2016	We report a case of crizotinib effectiveness in a heavily pretreated patient with a metastatic NSCLC initially considered IHC-positive and FISH-negative for ALK rearrangement.	Crizotinib	20-30	ALK receptor tyrosine kinase	Homo sapiens	157-160
27328934-1	2016	UNLABELLED: : On March 11, 2016, after an expedited 5-month review, the U.S. Food and Drug Administration expanded the crizotinib metastatic non-small cell lung cancer (mNSCLC) indication to include the treatment of patients whose tumors harbor a ROS1 rearrangement.	Crizotinib	119-129	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	247-251
27328934-11	2016	IMPLICATIONS FOR PRACTICE: Given the results from the ROS1 cohort of the clinical trial PROFILE 1001, crizotinib represents a new treatment option and the first approved therapy for patients with metastatic non-small cell lung cancer whose tumors are ROS1 positive.	Crizotinib	102-112	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	54-58
27328934-11	2016	IMPLICATIONS FOR PRACTICE: Given the results from the ROS1 cohort of the clinical trial PROFILE 1001, crizotinib represents a new treatment option and the first approved therapy for patients with metastatic non-small cell lung cancer whose tumors are ROS1 positive.	Crizotinib	102-112	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	251-255
28330089-2	2016	Evidences available suggest that there is a development of an acquired resistance against crizotinib action due to the emergence of several mutations in the ALK gene.	Crizotinib	90-100	ALK receptor tyrosine kinase	Homo sapiens	157-160
26616860-1	2016	The crizotinib-resistant ALK(F1174L) mutation arises de novo in neuroblastoma (NB) and is acquired in ALK translocation-driven cancers, lending impetus to the development of novel anaplastic lymphoma kinase (ALK) inhibitors with different modes of action.	Crizotinib	4-14	ALK receptor tyrosine kinase	Homo sapiens	25-28
26616860-1	2016	The crizotinib-resistant ALK(F1174L) mutation arises de novo in neuroblastoma (NB) and is acquired in ALK translocation-driven cancers, lending impetus to the development of novel anaplastic lymphoma kinase (ALK) inhibitors with different modes of action.	Crizotinib	4-14	ALK receptor tyrosine kinase	Homo sapiens	102-105
26616860-1	2016	The crizotinib-resistant ALK(F1174L) mutation arises de novo in neuroblastoma (NB) and is acquired in ALK translocation-driven cancers, lending impetus to the development of novel anaplastic lymphoma kinase (ALK) inhibitors with different modes of action.	Crizotinib	4-14	ALK receptor tyrosine kinase	Homo sapiens	180-206
26616860-1	2016	The crizotinib-resistant ALK(F1174L) mutation arises de novo in neuroblastoma (NB) and is acquired in ALK translocation-driven cancers, lending impetus to the development of novel anaplastic lymphoma kinase (ALK) inhibitors with different modes of action.	Crizotinib	4-14	ALK receptor tyrosine kinase	Homo sapiens	102-105
26938871-1	2016	The next-generation ALK-TKI, alectinib, has been reported to have potent efficacy in ALK-positive NSCLC patients including on mutations that confer resistance to crizotinib, which was the first ALK-TKI approved for ALK-positive NSCLC.	Crizotinib	162-172	ALK receptor tyrosine kinase	Homo sapiens	20-23
27149990-8	2016	Five potential personalized drug target genes, which were spontaneously amplified loci in both murine and human basal-like tumors, were identified: Cul4a, Lamp1, Met, Pnpla6 and Tubgcp3 As a proof of concept, inhibition of Met using crizotinib caused Met-amplified murine tumors to initially undergo complete regression.	Crizotinib	233-243	cullin 4A	Homo sapiens	148-153
26988570-0	2016	Dramatic Response to Combination Erlotinib and Crizotinib in a Patient with Advanced, EGFR-Mutant Lung Cancer Harboring De Novo MET Amplification.	Crizotinib	47-57	epidermal growth factor receptor	Homo sapiens	86-90
27179848-1	2016	INTRODUCTION: The presence of ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1) rearrangements in lung cancers confers sensitivity to ROS kinase inhibitors, including crizotinib.	Crizotinib	176-186	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	30-76
27179848-1	2016	INTRODUCTION: The presence of ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1) rearrangements in lung cancers confers sensitivity to ROS kinase inhibitors, including crizotinib.	Crizotinib	176-186	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	83-87
27179848-9	2016	CONCLUSION: IHC staining can be used to screen for ROS1 gene rearrangements, with patients herein showing a response to crizotinib.	Crizotinib	120-130	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	51-55
27237026-0	2016	Clinical impact of crizotinib on central nervous system progression in ALK-positive non-small lung cancer.	Crizotinib	19-29	ALK receptor tyrosine kinase	Homo sapiens	71-74
27237026-1	2016	BACKGROUND: The central nervous system (CNS) is a preferential progression site related to poor penetration of crizotinib into the CNS in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) patients treated with crizotinib.	Crizotinib	111-121	ALK receptor tyrosine kinase	Homo sapiens	138-164
27237026-1	2016	BACKGROUND: The central nervous system (CNS) is a preferential progression site related to poor penetration of crizotinib into the CNS in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) patients treated with crizotinib.	Crizotinib	111-121	ALK receptor tyrosine kinase	Homo sapiens	166-169
27237026-2	2016	We evaluated the clinical impact of crizotinib on central nervous system progression in ALK-positive NSCLC.	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	88-91
27237026-12	2016	CONCLUSION: The common progression site in ALK-positive patients treated with crizotinib was the CNS.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	43-46
27237027-1	2016	Crizotinib was approved for the treatment of ROS1-rearranged non-small cell lung cancer (NSCLC) patients in the US on 11 March, 2016.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	45-49
27472693-0	2016	Response to crizotinib in a lung adenocarcinoma patient harboring EML4-ALK translocation with adnexal metastasis: A Case Report.	Crizotinib	12-22	EMAP like 4	Homo sapiens	66-70
27441079-0	2016	Three Years Sustained Complete Remission Achieved in a Primary Refractory ALK-Positive Anaplastic T Large Cell Lymphoma Treated with Crizotinib.	Crizotinib	133-143	ALK receptor tyrosine kinase	Homo sapiens	74-77
27441079-3	2016	Crizotinib is a selective ATP-competitive inhibitor for ALK, approved for its use in lung cancer with rearrangements on ALK gene.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	56-59
27441079-3	2016	Crizotinib is a selective ATP-competitive inhibitor for ALK, approved for its use in lung cancer with rearrangements on ALK gene.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	120-123
27441079-5	2016	We report a case of a primary refractory ALK+ anaplastic large-cell lymphoma that sustains complete response after 3 years of crizotinib monotherapy.	Crizotinib	126-136	ALK receptor tyrosine kinase	Homo sapiens	41-44
28210164-0	2016	Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	55-58
28210164-3	2016	Crizotinib is a tyrosine kinase inhibitor, targeting ALK, ROS1, RON, and MET.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	53-56
28210164-3	2016	Crizotinib is a tyrosine kinase inhibitor, targeting ALK, ROS1, RON, and MET.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	58-62
28210164-3	2016	Crizotinib is a tyrosine kinase inhibitor, targeting ALK, ROS1, RON, and MET.	Crizotinib	0-10	macrophage stimulating 1 receptor	Homo sapiens	64-67
28210164-6	2016	In 2013, the randomized Phase III trial PROFILE-1007 confirmed the efficacy of crizotinib in ALK-rearranged NSCLC, compared to cytotoxic chemotherapy, in second-line setting or more.	Crizotinib	79-89	ALK receptor tyrosine kinase	Homo sapiens	93-96
28210164-9	2016	Based on these results, crizotinib received approval from the FDA and European Medicines Agency for first-line treatment of ALK-rearranged NSCLC.	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	124-127
28210164-10	2016	The various molecular mechanisms at the time of the progression (ALK mutations or amplification, ALK-independent mechanisms) encourage performing re-biopsy at the time of progression under crizotinib.	Crizotinib	189-199	ALK receptor tyrosine kinase	Homo sapiens	65-68
28210164-10	2016	The various molecular mechanisms at the time of the progression (ALK mutations or amplification, ALK-independent mechanisms) encourage performing re-biopsy at the time of progression under crizotinib.	Crizotinib	189-199	ALK receptor tyrosine kinase	Homo sapiens	97-100
27366096-0	2016	Bilateral breast adenocarcinomas with EML4-ALK fusion in a patient with multiple metastases successfully treated with crizotinib: is lung the primary site?	Crizotinib	118-128	EMAP like 4	Homo sapiens	38-42
27366096-0	2016	Bilateral breast adenocarcinomas with EML4-ALK fusion in a patient with multiple metastases successfully treated with crizotinib: is lung the primary site?	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	43-46
27366096-4	2016	The patient was successfully treated with an ALK inhibitor (crizotinib); symptoms improved quickly after initiation of crizotinib therapy, and a partial response was observed after 3 months.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	45-48
27366096-4	2016	The patient was successfully treated with an ALK inhibitor (crizotinib); symptoms improved quickly after initiation of crizotinib therapy, and a partial response was observed after 3 months.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	45-48
27144340-0	2016	Metformin restores crizotinib sensitivity in crizotinib-resistant human lung cancer cells through inhibition of IGF1-R signaling pathway.	Crizotinib	19-29	insulin like growth factor 1	Homo sapiens	112-116
27144340-0	2016	Metformin restores crizotinib sensitivity in crizotinib-resistant human lung cancer cells through inhibition of IGF1-R signaling pathway.	Crizotinib	45-55	insulin like growth factor 1	Homo sapiens	112-116
27144340-1	2016	AIM: Despite the impressive efficacy of crizotinib for the treatment of ALK-positive non-small cell lung cancer, patients invariably develop therapeutic resistance.	Crizotinib	40-50	ALK receptor tyrosine kinase	Homo sapiens	72-75
27144340-2	2016	Suppression of the IGF-1R signaling pathway may abrogate this acquired mechanism of drug resistance to crizotinib.	Crizotinib	103-113	insulin like growth factor 1 receptor	Homo sapiens	19-25
27144340-3	2016	Metformin, a widely used antidiabetic agent, may reverse crizotinib resistance through inhibition of IGF-1R signaling.	Crizotinib	57-67	insulin like growth factor 1 receptor	Homo sapiens	101-107
27144340-5	2016	Metformin reduced IGF-1R signaling activation in crizotinib-resistant cells.	Crizotinib	49-59	insulin like growth factor 1 receptor	Homo sapiens	18-24
27144340-6	2016	Furthermore, the addition of IGF-1 to crizotinib-sensitive H2228 cells induced crizotinib resistance, which was overcome by metformin.	Crizotinib	38-48	insulin like growth factor 1	Homo sapiens	29-34
27144340-6	2016	Furthermore, the addition of IGF-1 to crizotinib-sensitive H2228 cells induced crizotinib resistance, which was overcome by metformin.	Crizotinib	79-89	insulin like growth factor 1	Homo sapiens	29-34
27144340-8	2016	CONCLUSIONS: Metformin may be used in combination with crizotinib in ALK+ NSCLC patients to overcome crizotinib resistance and prolong survival.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	69-72
27126828-4	2016	Several oral agents are used in treating patients with lung cancer driven by mutations of genes coding for anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR); currently available agents include the ALK inhibitors certinib and crizotinib and the EGFR inhibitors afatinib, erlotinib, and gefitinib.	Crizotinib	252-262	epidermal growth factor receptor	Homo sapiens	178-182
27126828-4	2016	Several oral agents are used in treating patients with lung cancer driven by mutations of genes coding for anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR); currently available agents include the ALK inhibitors certinib and crizotinib and the EGFR inhibitors afatinib, erlotinib, and gefitinib.	Crizotinib	252-262	ALK receptor tyrosine kinase	Homo sapiens	224-227
27133743-6	2016	Here we reported a crizotinib-refractory ALK-positive NSCLC patient who develop radiation necrosis in one of his metastatic CNS lesions after approximately 12 months of alectinib treatment who otherwise had on-going CNS response on alectinib.	Crizotinib	19-29	ALK receptor tyrosine kinase	Homo sapiens	41-44
26467669-1	2016	Crizotinib is a small molecule inhibitor of anaplastic lymphoma kinase (ALK) and can be used to treat ALK-positive nonsmall-cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Rattus norvegicus	44-70
26467669-1	2016	Crizotinib is a small molecule inhibitor of anaplastic lymphoma kinase (ALK) and can be used to treat ALK-positive nonsmall-cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Rattus norvegicus	72-75
26467669-1	2016	Crizotinib is a small molecule inhibitor of anaplastic lymphoma kinase (ALK) and can be used to treat ALK-positive nonsmall-cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Rattus norvegicus	102-105
26880708-0	2016	Is there a progression-free survival benefit of first-line crizotinib versus standard chemotherapy and second-line crizotinib in ALK-positive advanced lung adenocarcinoma?	Crizotinib	115-125	ALK receptor tyrosine kinase	Homo sapiens	129-132
26880708-9	2016	Thus, there was a significant PFS benefit of first-line crizotinib versus first-line standard chemotherapy in Chinese patients with ALK-positive lung adenocarcinoma.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	132-135
27122312-3	2016	AREAS COVERED: Three drugs have been approved for clinical use in ALK-positive patients - crizotinib, ceritinib and alectinib.	Crizotinib	90-100	ALK receptor tyrosine kinase	Homo sapiens	66-69
27109446-0	2016	Central nervous system involvement in ALK-rearranged NSCLC: promising strategies to overcome crizotinib resistance.	Crizotinib	93-103	ALK receptor tyrosine kinase	Homo sapiens	38-41
27109446-2	2016	These patients exhibit dramatic responses when treated with the ALK tyrosine kinase inhibitor Crizotinib, albeit Central Nervous System (CNS) activity is much less impressive than that observed against extracranial lesions.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	64-67
27109446-4	2016	Several novel generation ALK inhibitors have been developing to increase CNS penetration and to provide more complete ALK inhibition.. AREAS COVERED: The CNS activity of Crizotinib and novel generation ALK inhibitors will be summarized in this review, evaluating the strengths and weaknesses of the therapeutic strategies developed to date in this specific subgroup of NSCLCs with a look towards the future.	Crizotinib	170-180	ALK receptor tyrosine kinase	Homo sapiens	25-28
27109446-4	2016	Several novel generation ALK inhibitors have been developing to increase CNS penetration and to provide more complete ALK inhibition.. AREAS COVERED: The CNS activity of Crizotinib and novel generation ALK inhibitors will be summarized in this review, evaluating the strengths and weaknesses of the therapeutic strategies developed to date in this specific subgroup of NSCLCs with a look towards the future.	Crizotinib	170-180	ALK receptor tyrosine kinase	Homo sapiens	118-121
27109446-4	2016	Several novel generation ALK inhibitors have been developing to increase CNS penetration and to provide more complete ALK inhibition.. AREAS COVERED: The CNS activity of Crizotinib and novel generation ALK inhibitors will be summarized in this review, evaluating the strengths and weaknesses of the therapeutic strategies developed to date in this specific subgroup of NSCLCs with a look towards the future.	Crizotinib	170-180	ALK receptor tyrosine kinase	Homo sapiens	118-121
27245569-0	2016	Comprehensive Genomic Profiling Identifies a Subset of Crizotinib-Responsive ALK-Rearranged Non-Small Cell Lung Cancer Not Detected by Fluorescence In Situ Hybridization.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	77-80
27472693-0	2016	Response to crizotinib in a lung adenocarcinoma patient harboring EML4-ALK translocation with adnexal metastasis: A Case Report.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	71-74
27472693-2	2016	Crizotinib, a novel ALK tyrosine kinase inhibitor, has already shown an impressive single-agent activity in ALK positive lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	20-23
27472693-2	2016	Crizotinib, a novel ALK tyrosine kinase inhibitor, has already shown an impressive single-agent activity in ALK positive lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	108-111
27053502-1	2016	UNLABELLED: : The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	83-109
27053502-1	2016	UNLABELLED: : The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	111-114
27053502-1	2016	UNLABELLED: : The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	186-189
27245569-13	2016	Given the proven benefit of treatment with crizotinib and second-generation ALK inhibitors in patients with ALK fusions, CGP should be considered in patients with NSCLC, including those who have tested negative for other alterations, including negative results using ALK FISH testing.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	108-111
27245569-13	2016	Given the proven benefit of treatment with crizotinib and second-generation ALK inhibitors in patients with ALK fusions, CGP should be considered in patients with NSCLC, including those who have tested negative for other alterations, including negative results using ALK FISH testing.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	108-111
27413712-9	2016	Clinical behaviors of ALK-rearranged NSCLC vary significantly among patients and differential molecular events responsible of crizotinib resistance account for the most important quote of this heterogeneity.	Crizotinib	126-136	ALK receptor tyrosine kinase	Homo sapiens	22-25
27284449-1	2016	Crizotinib is a tyrosine kinase inhibitor that displays antitumor activity against anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	111-114
27078848-9	2016	Furthermore, CRKL tyrosine phosphorylation was inhibited by dasatinib (an inhibitor of ABL and SRC kinases), which in combination with the ALK inhibitor crizotinib displayed a synergistic inhibitory effect in vitro.	Crizotinib	153-163	CRK like proto-oncogene, adaptor protein	Homo sapiens	13-17
27413712-1	2016	Crizotinib is an oral inhibitor of anaplastic lymphoma kinase (ALK) with remarkable clinical activity in patients suffering from ALK-rearranged non-small cell lung cancer (NSCLC), accounting to its superiority compared to chemotherapy.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	35-61
27413712-1	2016	Crizotinib is an oral inhibitor of anaplastic lymphoma kinase (ALK) with remarkable clinical activity in patients suffering from ALK-rearranged non-small cell lung cancer (NSCLC), accounting to its superiority compared to chemotherapy.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	63-66
27413712-1	2016	Crizotinib is an oral inhibitor of anaplastic lymphoma kinase (ALK) with remarkable clinical activity in patients suffering from ALK-rearranged non-small cell lung cancer (NSCLC), accounting to its superiority compared to chemotherapy.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	129-132
27413712-2	2016	Unfortunately, virtually all ALK-rearranged tumors acquire resistance to crizotinib, frequently within one year since the treatment initiation.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	29-32
27049722-3	2016	Crizotinib, the first clinically approved ALK inhibitor for the treatment of ALK-positive lung cancer has had less dramatic responses in neuroblastoma.	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	42-45
27078848-9	2016	Furthermore, CRKL tyrosine phosphorylation was inhibited by dasatinib (an inhibitor of ABL and SRC kinases), which in combination with the ALK inhibitor crizotinib displayed a synergistic inhibitory effect in vitro.	Crizotinib	153-163	ABL proto-oncogene 1, non-receptor tyrosine kinase	Homo sapiens	87-90
27078848-9	2016	Furthermore, CRKL tyrosine phosphorylation was inhibited by dasatinib (an inhibitor of ABL and SRC kinases), which in combination with the ALK inhibitor crizotinib displayed a synergistic inhibitory effect in vitro.	Crizotinib	153-163	ALK receptor tyrosine kinase	Homo sapiens	139-142
26673800-1	2016	PURPOSE: Rearranged ROS1 is a crizotinib-sensitive oncogenic driver in lung cancer.	Crizotinib	30-40	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	20-24
26673800-4	2016	EXPERIMENTAL DESIGN: We report the discovery of a novel, solvent-front ROS1(D2033N) mutation in a patient with CD74-ROS1-rearranged lung adenocarcinoma and acquired resistance to crizotinib.	Crizotinib	179-189	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	71-75
26673800-4	2016	EXPERIMENTAL DESIGN: We report the discovery of a novel, solvent-front ROS1(D2033N) mutation in a patient with CD74-ROS1-rearranged lung adenocarcinoma and acquired resistance to crizotinib.	Crizotinib	179-189	CD74 molecule	Homo sapiens	111-115
26673800-4	2016	EXPERIMENTAL DESIGN: We report the discovery of a novel, solvent-front ROS1(D2033N) mutation in a patient with CD74-ROS1-rearranged lung adenocarcinoma and acquired resistance to crizotinib.	Crizotinib	179-189	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	116-120
26673800-5	2016	Crizotinib resistance of CD74-ROS1(D2033N) was functionally evaluated using cell-based assays and structural modeling.	Crizotinib	0-10	CD74 molecule	Homo sapiens	25-29
26673800-5	2016	Crizotinib resistance of CD74-ROS1(D2033N) was functionally evaluated using cell-based assays and structural modeling.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	30-34
26673800-6	2016	RESULTS: In biochemical and cell-based assays, the CD74-ROS1(D2033N) mutant demonstrated significantly decreased sensitivity to crizotinib.	Crizotinib	128-138	CD74 molecule	Homo sapiens	51-55
26673800-6	2016	RESULTS: In biochemical and cell-based assays, the CD74-ROS1(D2033N) mutant demonstrated significantly decreased sensitivity to crizotinib.	Crizotinib	128-138	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	56-60
26673800-10	2016	CONCLUSIONS: These results provide the first example of successful therapeutic intervention with targeted therapy to overcome crizotinib resistance in a ROS1-rearranged cancer.	Crizotinib	126-136	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	153-157
27137772-1	2016	BACKGROUND: In ALK-positive advanced NSCLC, crizotinib has a high response rate and effectively increases quality of life and survival.	Crizotinib	44-54	ALK receptor tyrosine kinase	Homo sapiens	15-18
27594959-1	2016	Crizotinib has been approved for the treatment of advanced ALK-positive non-small cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	59-62
27594959-4	2016	Here, we describe a case of a patient with ALK-positive advanced non-small cell lung cancer who developed complex renal cyst during crizotinib treatment.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	43-46
27217763-3	2016	Crizotinib was the first ALK tyrosine kinase inhibitor licensed for the treatment of metastatic ALK-positive NSCLC based on a randomized Phase III trial.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	25-28
27217763-3	2016	Crizotinib was the first ALK tyrosine kinase inhibitor licensed for the treatment of metastatic ALK-positive NSCLC based on a randomized Phase III trial.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	96-99
27217763-8	2016	Ceritinib is an oral second-generation ALK inhibitor showing clinical activity not only in crizotinib-resistant ALK-positive NSCLC but also in treatment-naive ALK-positive disease.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	112-115
27217763-8	2016	Ceritinib is an oral second-generation ALK inhibitor showing clinical activity not only in crizotinib-resistant ALK-positive NSCLC but also in treatment-naive ALK-positive disease.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	112-115
26964870-5	2016	Tumors developed progressively in the untreated TG mice of both lines, whereas those receiving oral administration of an ALK/MET/ROS1 inhibitor, crizotinib, and an ALK/ROS1 inhibitor, ASP3026, showed marked reduction in the tumor burden.	Crizotinib	145-155	Ros1 proto-oncogene	Mus musculus	129-133
27142166-12	2016	Crizotinib therapy provided treatment benefit in ALK-rearranged adenocarcinoma patients especially in advanced stages of the disease.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	49-52
26923554-4	2016	KRCA-386 has superior inhibitory activity against ALK mutants commonly found in crizotinib-resistant patients.	Crizotinib	80-90	ALK receptor tyrosine kinase	Homo sapiens	50-53
26943457-2	2016	The dramatic benefits of crizotinib have prompted research into identifying other possible patients carrying ALK gene alterations with possible clinical significance.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	109-112
26454342-2	2016	This study explored ALK variants and the percentage of ALK-positive cells using fluorescent in situ hybridization (FISH) on clinical efficacy of crizotinib.	Crizotinib	145-155	ALK receptor tyrosine kinase	Homo sapiens	20-23
26454342-2	2016	This study explored ALK variants and the percentage of ALK-positive cells using fluorescent in situ hybridization (FISH) on clinical efficacy of crizotinib.	Crizotinib	145-155	ALK receptor tyrosine kinase	Homo sapiens	55-58
26454342-13	2016	The percentage of ALK-positive cells might correlate with the extent of benefit from crizotinib treatment.	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	18-21
27040846-1	2016	We report two cases of acute hepatitis induced by crizotinib in patients with ALK-rearranged non-small cell lung cancer (NSCLC) who were treated after by a second generation of ALK inhibitor without any incident.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	78-81
26888425-1	2016	AIM: The ALK inhibitor, crizotinib, has demonstrated effectiveness in patients with non-small-cell lung cancer harboring ALK rearrangements.	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	9-12
26888425-1	2016	AIM: The ALK inhibitor, crizotinib, has demonstrated effectiveness in patients with non-small-cell lung cancer harboring ALK rearrangements.	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	121-124
26808369-0	2016	Complete and Repeated Response of a Metastatic ALK-rearranged Inflammatory Myofibroblastic Tumor to Crizotinib in a Teenage Girl.	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	47-50
26752677-3	2016	Herein, we report a case of ALK-rearranged lung adenocarcinoma with SCLC-like histology in a metastatic abdominal nodule that was resistant to crizotinib therapy.	Crizotinib	143-153	ALK receptor tyrosine kinase	Homo sapiens	28-31
27040846-1	2016	We report two cases of acute hepatitis induced by crizotinib in patients with ALK-rearranged non-small cell lung cancer (NSCLC) who were treated after by a second generation of ALK inhibitor without any incident.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	177-180
27040858-3	2016	At the first line therapy, the patient was treated with crizotinib because of the KRAS mutation that is a known resistant factor of EGFR-TKI resistance, but no responsive.	Crizotinib	56-66	KRAS proto-oncogene, GTPase	Homo sapiens	82-86
27040858-3	2016	At the first line therapy, the patient was treated with crizotinib because of the KRAS mutation that is a known resistant factor of EGFR-TKI resistance, but no responsive.	Crizotinib	56-66	epidermal growth factor receptor	Homo sapiens	132-136
27239236-2	2016	EGFR tyrosine kinase inhibitors (TKIs) and crizotinib are the standard of care for the treatment of EGFR mutant and ALK gene rearranged advanced NSCLC patients.	Crizotinib	43-53	epidermal growth factor receptor	Homo sapiens	100-104
27239236-2	2016	EGFR tyrosine kinase inhibitors (TKIs) and crizotinib are the standard of care for the treatment of EGFR mutant and ALK gene rearranged advanced NSCLC patients.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	116-119
26993609-9	2016	Sequential CTC counts in an index case of lung cancer with no evaluable tumor tissue treated with crizotinib showed six, three and eleven ALK-positive CTCs per 1.88 mL blood at baseline, partial response and post-progression time points, respectively.	Crizotinib	98-108	ALK receptor tyrosine kinase	Homo sapiens	138-141
27045755-1	2016	ALK-break positive non-small cell lung cancer (NSCLC) patients initially respond to crizotinib, but resistance occurs inevitably.	Crizotinib	84-94	ALK receptor tyrosine kinase	Homo sapiens	0-3
27148422-0	2016	Response to crizotinib in a squamous cell lung carcinoma patient harbouring echinoderm microtubule-associated protein-like 4-anaplastic lymphoma translocation: A case report.	Crizotinib	12-22	EMAP like 4	Homo sapiens	76-124
27148422-2	2016	We present a case of ALK gene translocation-SCC in which a remarkable tumor response to crizotinib was achieved after the failure of prior chemoradiotherapy.	Crizotinib	88-98	ALK receptor tyrosine kinase	Homo sapiens	21-24
27148422-2	2016	We present a case of ALK gene translocation-SCC in which a remarkable tumor response to crizotinib was achieved after the failure of prior chemoradiotherapy.	Crizotinib	88-98	serpin family B member 3	Homo sapiens	44-47
27003761-2	2016	Despite the remarkable clinical activity of crizotinib (Xalkori), the first ALK inhibitor approved in 2011, the emergence of resistance mutations and of brain metastases frequently causes relapse in patients.	Crizotinib	44-54	ALK receptor tyrosine kinase	Homo sapiens	76-79
27070423-7	2016	RESULTS: HCC827 (Exon19: E746-A750 del) and H3122 (EML4-ALK) cells were inhibited by lower concentrations of erlotinib and crizotinib, respectively than A549, H460, and H1975 (L858R+T790M) cells were.	Crizotinib	123-133	EMAP like 4	Homo sapiens	51-55
27070423-7	2016	RESULTS: HCC827 (Exon19: E746-A750 del) and H3122 (EML4-ALK) cells were inhibited by lower concentrations of erlotinib and crizotinib, respectively than A549, H460, and H1975 (L858R+T790M) cells were.	Crizotinib	123-133	ALK receptor tyrosine kinase	Homo sapiens	56-59
27045755-14	2016	The detection of ALK mutations in post-treatment tumor samples of two patients underlines their role in crizotinib resistance.	Crizotinib	104-114	ALK receptor tyrosine kinase	Homo sapiens	17-20
26852079-1	2016	Targeted treatment of advanced non-small cell lung cancer patients with afatinib in EGFR mutation or crizotinib in ALK break positive patients results in profound tumor responses but inevitably induces resistance.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	115-118
26892300-3	2016	Crizotinib was the first ALK inhibitor showing pronounced clinical activity, and is now a reference treatment for ALK-positive NSCLC disease.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	25-28
26892300-3	2016	Crizotinib was the first ALK inhibitor showing pronounced clinical activity, and is now a reference treatment for ALK-positive NSCLC disease.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	114-117
26677785-0	2016	Durable brain response with pulse-dose crizotinib and ceritinib in ALK-positive non-small cell lung cancer compared with brain radiotherapy.	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	67-70
26677785-1	2016	Crizotinib achieves excellent systemic control in anaplastic lymphoma kinase-rearranged (ALK+) non-small cell lung cancer (NSCLC); however, central nervous system (CNS) metastases frequently occur as an early event.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	89-92
26677785-3	2016	We present a case series of three ALK+ NSCLC patients with progressing CNS metastases who were treated with pulse-dose crizotinib followed by ceritinib.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	34-37
26677785-10	2016	Manipulating the crizotinib schedule in ALK+ NSCLC patients with CNS metastases and using a novel ALK-inhibitor at the time of further progression may provide durable CNS control and allow brain radiotherapy to be deferred.	Crizotinib	17-27	ALK receptor tyrosine kinase	Homo sapiens	40-43
26973202-1	2016	OBJECTIVES: Chromosomal rearrangements of ALK and ROS1 genes in non-small cell lung carcinoma (NSCLC) define a molecular subgroup of lung adenocarcinoma (ADC) that is amenable to targeted therapy with tyrosine kinase inhibitors (TKIs) crizotinib.	Crizotinib	235-245	ALK receptor tyrosine kinase	Homo sapiens	42-45
26973202-1	2016	OBJECTIVES: Chromosomal rearrangements of ALK and ROS1 genes in non-small cell lung carcinoma (NSCLC) define a molecular subgroup of lung adenocarcinoma (ADC) that is amenable to targeted therapy with tyrosine kinase inhibitors (TKIs) crizotinib.	Crizotinib	235-245	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	50-54
26639656-2	2016	For patients with ALK positive NCSLC, crizotinib and ceritinib are FDA approved ALK inhibitors, however, patients inevitably acquire resistance to such therapies typically within one to two years.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	18-21
26939704-1	2016	Activated ALK and ROS1 tyrosine kinases, resulting from chromosomal rearrangements, occur in a subset of non-small cell lung cancers (NSCLC) as well as other tumor types and their oncogenic relevance as actionable targets has been demonstrated by the efficacy of selective kinase inhibitors such as crizotinib, ceritinib, and alectinib.	Crizotinib	299-309	ALK receptor tyrosine kinase	Homo sapiens	10-13
26939704-1	2016	Activated ALK and ROS1 tyrosine kinases, resulting from chromosomal rearrangements, occur in a subset of non-small cell lung cancers (NSCLC) as well as other tumor types and their oncogenic relevance as actionable targets has been demonstrated by the efficacy of selective kinase inhibitors such as crizotinib, ceritinib, and alectinib.	Crizotinib	299-309	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	18-22
26639656-2	2016	For patients with ALK positive NCSLC, crizotinib and ceritinib are FDA approved ALK inhibitors, however, patients inevitably acquire resistance to such therapies typically within one to two years.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	80-83
26639656-6	2016	In addition, HSP90 inhibitors ganetespib and 17-AAG were potent in inducing cell death in cell lines resistant to crizotinib and ceritinib.	Crizotinib	114-124	heat shock protein 90 alpha family class A member 1	Homo sapiens	13-18
26499783-7	2016	Moreover, both EGCG and miR-1 mimic inhibited c-MET expression, and combination treatment with EGCG and c-MET inhibitor (crizotinib) had enhanced inhibitory effects on the growth of MG-63 and U-2OS cells.	Crizotinib	121-131	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	104-109
27069372-3	2016	Ceritinib (Zykadia ) was granted accelerated approval by the US Food and Drug Administration in 2014 for treating crizotinib-resistant ALK-positive NSCLC.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	135-138
27057482-0	2016	cMET inhibitor crizotinib impairs angiogenesis and reduces tumor burden in the C3(1)-Tag model of basal-like breast cancer.	Crizotinib	15-25	met proto-oncogene	Mus musculus	0-4
27057482-9	2016	In sum, cMET inhibition by crizotinib limited tumor development and microvascular density in basal-like tumor-bearing mice but did not appear to be an effective preventive agent for BBC.	Crizotinib	27-37	met proto-oncogene	Mus musculus	8-12
26719536-1	2016	Crizotinib is the standard of care for advanced non-small cell lung cancer (NSCLC) patients harboring the anaplastic lymphoma kinase (ALK) fusion gene, but resistance invariably develops.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	106-132
26719536-1	2016	Crizotinib is the standard of care for advanced non-small cell lung cancer (NSCLC) patients harboring the anaplastic lymphoma kinase (ALK) fusion gene, but resistance invariably develops.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	134-137
26968843-16	2016	Intratumoral heterogeneity for ALK rearrangement suggests a limitation of single-biopsy analysis for therapeutic strategy with crizotinib.	Crizotinib	127-137	ALK receptor tyrosine kinase	Homo sapiens	31-34
26802023-0	2016	ALK and ROS1 as targeted therapy paradigms and clinical implications to overcome crizotinib resistance.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	0-3
26802023-0	2016	ALK and ROS1 as targeted therapy paradigms and clinical implications to overcome crizotinib resistance.	Crizotinib	81-91	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	8-12
26802023-3	2016	Inhibition of ALK and ROS1 by crizotinib has been reported to be highly effective and well tolerated in these patients.	Crizotinib	30-40	ALK receptor tyrosine kinase	Homo sapiens	14-17
26802023-3	2016	Inhibition of ALK and ROS1 by crizotinib has been reported to be highly effective and well tolerated in these patients.	Crizotinib	30-40	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	22-26
26966027-1	2016	BACKGROUND: ASP3026 is a second-generation anaplastic lymphoma kinase (ALK) inhibitor that has potent in vitro activity against crizotinib-resistant ALK-positive tumors.	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	43-69
26966027-1	2016	BACKGROUND: ASP3026 is a second-generation anaplastic lymphoma kinase (ALK) inhibitor that has potent in vitro activity against crizotinib-resistant ALK-positive tumors.	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	71-74
26966027-1	2016	BACKGROUND: ASP3026 is a second-generation anaplastic lymphoma kinase (ALK) inhibitor that has potent in vitro activity against crizotinib-resistant ALK-positive tumors.	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	149-152
26966027-5	2016	A phase Ib expansion cohort enrolled patients with metastatic, crizotinib-resistant ALK-positive solid tumors at the RP2D, and response was evaluated by RECIST 1.1.	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	84-87
26966027-10	2016	Among the 16 patients with crizotinib-resistant ALK-positive tumors (15 NSCLC, 1 neuroblastoma), eight patients achieved partial response (overall response rate 50%; 95% confidence interval 25-75%) and seven patients (44%) achieved stable disease.	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	48-51
26966027-11	2016	CONCLUSIONS: ASP3026 was well tolerated and had therapeutic activity in patients with crizotinib-resistant ALK-positive advanced tumors.	Crizotinib	86-96	ALK receptor tyrosine kinase	Homo sapiens	107-110
27065847-1	2016	We report on a 90-year-old male patient with a ROS1-translocated adenocarcinoma of the lung who was treated with crizotinib as first-line therapy.	Crizotinib	113-123	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	47-51
26951079-1	2016	Crizotinib as the first-generation ALK inhibitor has shown significant activity in ALK-mutated non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	35-38
26951079-1	2016	Crizotinib as the first-generation ALK inhibitor has shown significant activity in ALK-mutated non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	83-86
26951079-3	2016	In addition, a third-generation ALK inhibitor, lorlatinib (PF-06463922), was reported to resensitize NSCLC to crizotinib.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	32-35
26781210-10	2016	In addition, treatment with a combination of afatinib with either c-MET inhibitor Crizotinib or Stattic resulted in an additive or synergistic growth inhibition in all three variants.	Crizotinib	82-92	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	66-71
26973324-1	2016	BACKGROUND: ALK-rearranged non-small-cell lung cancer (NSCLC) is sensitive to ALK tyrosine kinase inhibitors (ALK inhibitors) such as crizotinib, but resistance invariably develops, often with progression in the brain.	Crizotinib	134-144	ALK receptor tyrosine kinase	Homo sapiens	12-15
26973324-1	2016	BACKGROUND: ALK-rearranged non-small-cell lung cancer (NSCLC) is sensitive to ALK tyrosine kinase inhibitors (ALK inhibitors) such as crizotinib, but resistance invariably develops, often with progression in the brain.	Crizotinib	134-144	ALK receptor tyrosine kinase	Homo sapiens	78-81
26973324-1	2016	BACKGROUND: ALK-rearranged non-small-cell lung cancer (NSCLC) is sensitive to ALK tyrosine kinase inhibitors (ALK inhibitors) such as crizotinib, but resistance invariably develops, often with progression in the brain.	Crizotinib	134-144	ALK receptor tyrosine kinase	Homo sapiens	78-81
26849637-11	2016	CONCLUSION: These results indicated that alectinib has potent antitumor activity against NSCLC cells harboring the crizotinib-resistant mutation ALK G1269A.	Crizotinib	115-125	ALK receptor tyrosine kinase	Homo sapiens	145-148
26849637-12	2016	It is expected that alectinib would provide a valuable therapeutic option for patients with NSCLC having not only native ALK but also crizotinib-resistant ALK mutations.	Crizotinib	134-144	ALK receptor tyrosine kinase	Homo sapiens	155-158
26729443-11	2016	A patient whose lung cancer harbored a MET exon 14 mutation with concurrent genomic amplification of the mutated MET allele experienced a major partial response to the c-Met inhibitor crizotinib.	Crizotinib	184-194	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	168-173
26598747-0	2016	Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	35-38
26598747-1	2016	PURPOSE: Crizotinib confers improved progression-free survival compared with chemotherapy in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC), but progression invariably occurs.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	121-124
26598747-14	2016	CONCLUSION: Alectinib is highly active and well tolerated in patients with advanced, crizotinib-refractory ALK-positive NSCLC, including those with CNS metastases.	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	107-110
27134984-2	2016	These tumours are particularly sensitive to Alk-targeted therapies, as crizotinib.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	44-47
27134984-4	2016	We report a case of fatal haemoptysis associated with dramatic response to crizotinib in a patient with an ALK-rearranged lung adenocarcinoma.	Crizotinib	75-85	ALK receptor tyrosine kinase	Homo sapiens	107-110
26898609-3	2016	Serum aspartate aminotransferase and alanine aminotransferase levels had increased from normal prior to crizotinib start to 2053 IU/L and 6194 IU/L, respectively.	Crizotinib	104-114	glutamic--pyruvic transaminase	Homo sapiens	37-61
26898615-0	2016	K-RAS mutations indicating primary resistance to crizotinib in ALK-rearranged adenocarcinomas of the lung: Report of two cases and review of the literature.	Crizotinib	49-59	KRAS proto-oncogene, GTPase	Homo sapiens	0-5
26898615-0	2016	K-RAS mutations indicating primary resistance to crizotinib in ALK-rearranged adenocarcinomas of the lung: Report of two cases and review of the literature.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	63-66
26898615-4	2016	Search for similar cases in the literature reveals that concomitant K-RAS mutations and ALK rearrangement occur in a subset of NSCLC and seems to lead to resistance to crizotinib.	Crizotinib	168-178	KRAS proto-oncogene, GTPase	Homo sapiens	68-73
26898615-4	2016	Search for similar cases in the literature reveals that concomitant K-RAS mutations and ALK rearrangement occur in a subset of NSCLC and seems to lead to resistance to crizotinib.	Crizotinib	168-178	ALK receptor tyrosine kinase	Homo sapiens	88-91
26992917-1	2016	Crizotinib is the first anaplastic lymphoma kinase (ALK) inhibitor to have been approved for the treatment of non-small cell lung cancer (NSCLC) harboring an ALK fusion gene, but it has been found that, in the clinic, patients develop resistance to it.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	24-50
26992917-1	2016	Crizotinib is the first anaplastic lymphoma kinase (ALK) inhibitor to have been approved for the treatment of non-small cell lung cancer (NSCLC) harboring an ALK fusion gene, but it has been found that, in the clinic, patients develop resistance to it.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	52-55
26992917-1	2016	Crizotinib is the first anaplastic lymphoma kinase (ALK) inhibitor to have been approved for the treatment of non-small cell lung cancer (NSCLC) harboring an ALK fusion gene, but it has been found that, in the clinic, patients develop resistance to it.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	158-161
26992917-2	2016	Alectinib and ceritinib are second-generation ALK inhibitors which show remarkable clinical responses in both crizotinib-naive and crizotinib-resistant NSCLC patients harboring an ALK fusion gene.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	46-49
26992917-2	2016	Alectinib and ceritinib are second-generation ALK inhibitors which show remarkable clinical responses in both crizotinib-naive and crizotinib-resistant NSCLC patients harboring an ALK fusion gene.	Crizotinib	131-141	ALK receptor tyrosine kinase	Homo sapiens	46-49
26992917-2	2016	Alectinib and ceritinib are second-generation ALK inhibitors which show remarkable clinical responses in both crizotinib-naive and crizotinib-resistant NSCLC patients harboring an ALK fusion gene.	Crizotinib	131-141	ALK receptor tyrosine kinase	Homo sapiens	180-183
26992917-6	2016	Although mutations of ALK in its kinase domain are a common resistance mechanism for crizotinib, we did not detect any ALK mutation in these resistant cell lines.	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	22-25
27009821-14	2016	The treatment of crizotinib-resistant patients using 2nd/3rd generation ALK-TKI could delay progression.	Crizotinib	17-27	ALK receptor tyrosine kinase	Homo sapiens	72-75
26438783-2	2016	The emergence of ALK inhibitors such as crizotinib has provided novel treatment opportunities.	Crizotinib	40-50	ALK receptor tyrosine kinase	Homo sapiens	17-20
26438783-3	2016	However, certain ALK mutations result in de novo crizotinib resistance, and a phase I trial of crizotinib showed a lack of response in patients harboring those ALK mutations.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	17-20
26438783-3	2016	However, certain ALK mutations result in de novo crizotinib resistance, and a phase I trial of crizotinib showed a lack of response in patients harboring those ALK mutations.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	160-163
26438783-5	2016	EXPERIMENTAL DESIGN: The sensitivity of human neuroblastoma-derived cell lines, cell line-derived, and patient-derived xenograft (PDX) models with varying ALK statuses to crizotinib combined with topotecan and cyclophosphamide (topo/cyclo) was examined.	Crizotinib	171-181	ALK receptor tyrosine kinase	Homo sapiens	155-158
26438783-8	2016	Crizotinib + topo/cyclo showed synergistic cytotoxicity and higher caspase-dependent apoptosis than crizotinib or topo/cyclo alone in neuroblastoma cell lines with ALK aberrations (mutation or amplification).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	164-167
26438783-9	2016	CONCLUSIONS: Combining crizotinib with chemotherapeutic agents commonly used in treating newly diagnosed patients with high-risk neuroblastoma restores sensitivity in preclinical models harboring both sensitive ALK aberrations and de novo-resistant ALK mutations.	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	211-214
26438783-9	2016	CONCLUSIONS: Combining crizotinib with chemotherapeutic agents commonly used in treating newly diagnosed patients with high-risk neuroblastoma restores sensitivity in preclinical models harboring both sensitive ALK aberrations and de novo-resistant ALK mutations.	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	249-252
26438783-10	2016	These data support clinical testing of crizotinib and conventional chemotherapy with the goal of integrating ALK inhibition into multiagent therapy for ALK-aberrant neuroblastoma patients.	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	109-112
26438783-10	2016	These data support clinical testing of crizotinib and conventional chemotherapy with the goal of integrating ALK inhibition into multiagent therapy for ALK-aberrant neuroblastoma patients.	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	152-155
26764587-0	2016	Directly Binding Rather than Induced-Fit Dominated Binding Affinity Difference in (S)- and (R)-Crizotinib Bound MTH1.	Crizotinib	95-105	nudix hydrolase 1	Homo sapiens	112-116
26764587-1	2016	As one of the most successful anticancer drugs, crizotinib is found to be efficient in the suppression of MTH1, a new therapeutic target for RAS-dependent cancers.	Crizotinib	48-58	nudix hydrolase 1	Homo sapiens	106-110
26764587-2	2016	Deep analysis shows that stereospecificity is prevalent in the binding of crizotinib to MTH1, where the target is more preferred to bind with the (S)-enantiomer of crizotinib.	Crizotinib	74-84	nudix hydrolase 1	Homo sapiens	88-92
26764587-2	2016	Deep analysis shows that stereospecificity is prevalent in the binding of crizotinib to MTH1, where the target is more preferred to bind with the (S)-enantiomer of crizotinib.	Crizotinib	164-174	nudix hydrolase 1	Homo sapiens	88-92
26764587-5	2016	Thereafter, by using advanced all-atom molecular dynamics simulations, we characterized the free energy surfaces of the binding/unbinding processes of the (S) and (R)-crizotinib enantiomers to/from MTH1.	Crizotinib	163-177	nudix hydrolase 1	Homo sapiens	198-202
26850068-7	2016	This deduction was supported by the repeated response to ALK inhibitors (crizotinib then AP26113) of the hepatic metastases.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	57-60
26848584-6	2016	When MET activities were suppressed by using the small-molecular inhibitor drug PF-02341066 (Crizotinib), the anchorage-independent MDCK-siat7e cells reverted to the cellular morphology of the parental anchorage-dependent MDCK cells.	Crizotinib	93-103	ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 5	Homo sapiens	137-143
26822904-0	2016	[Crizotinib: At last in first-line treatment of advanced-stage ALK-rearranged non-small cell lung cancer].	Crizotinib	1-11	ALK receptor tyrosine kinase	Homo sapiens	63-66
26845121-0	2016	Acquired EGFR Mutation as the Potential Resistance Driver to Crizotinib in a MET-Mutated Tumor.	Crizotinib	61-71	epidermal growth factor receptor	Homo sapiens	9-13
26215952-8	2016	Short interfering RNA silencing of MET and MET inhibition with crizotinib showed marked effects on cell viability and decrease in downstream AKT and mitogen-activated protein kinase activation in Hs746T and H596 cells.	Crizotinib	63-73	AKT serine/threonine kinase 1	Homo sapiens	141-144
26708155-16	2016	Therefore, alectinib could be a suitable treatment for patients with ALK-positive disease who have progressed on crizotinib.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	69-72
26775590-1	2016	A 63-year-old caucasian woman, presenting with metastatic primitive lung adenocarcinoma was treated with ALK inhibitor crizotinib treatment for six month.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	105-108
26775590-4	2016	It was associated with acquired resistance to crizotinib with ALK-rearrangement but without point mutation or amplification of the ALK gene.	Crizotinib	46-56	ALK receptor tyrosine kinase	Homo sapiens	62-65
26775590-5	2016	We herein report the first case of histological neuroendocrine transformation after ALK inhibitor crizotinib treatment, associated with acquired resistance to crizotinib.	Crizotinib	98-108	ALK receptor tyrosine kinase	Homo sapiens	84-87
26775590-5	2016	We herein report the first case of histological neuroendocrine transformation after ALK inhibitor crizotinib treatment, associated with acquired resistance to crizotinib.	Crizotinib	159-169	ALK receptor tyrosine kinase	Homo sapiens	84-87
26775591-0	2016	A novel acquired ALK F1245C mutation confers resistance to crizotinib in ALK-positive NSCLC but is sensitive to ceritinib.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	17-20
26775591-0	2016	A novel acquired ALK F1245C mutation confers resistance to crizotinib in ALK-positive NSCLC but is sensitive to ceritinib.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	73-76
26775591-1	2016	The emergence of acquired anaplastic lymphoma kinase (ALK) resistant mutations is a common molecular mechanism underpinning disease progression during crizotinib treatment of ALK-positive (ALK+) non-small cell lung cancer (NSCLC) patients.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	26-52
26775591-1	2016	The emergence of acquired anaplastic lymphoma kinase (ALK) resistant mutations is a common molecular mechanism underpinning disease progression during crizotinib treatment of ALK-positive (ALK+) non-small cell lung cancer (NSCLC) patients.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	54-57
26775591-1	2016	The emergence of acquired anaplastic lymphoma kinase (ALK) resistant mutations is a common molecular mechanism underpinning disease progression during crizotinib treatment of ALK-positive (ALK+) non-small cell lung cancer (NSCLC) patients.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	175-178
26775591-1	2016	The emergence of acquired anaplastic lymphoma kinase (ALK) resistant mutations is a common molecular mechanism underpinning disease progression during crizotinib treatment of ALK-positive (ALK+) non-small cell lung cancer (NSCLC) patients.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	175-178
26775591-4	2016	Here we described the emergence of an ALK F1245C mutation in an advanced ALK+ NSCLC patient (EML4-ALK variant 3a/b) who developed slow disease progression after a durable response to crizotinib.	Crizotinib	183-193	ALK receptor tyrosine kinase	Homo sapiens	38-41
26775591-4	2016	Here we described the emergence of an ALK F1245C mutation in an advanced ALK+ NSCLC patient (EML4-ALK variant 3a/b) who developed slow disease progression after a durable response to crizotinib.	Crizotinib	183-193	ALK receptor tyrosine kinase	Homo sapiens	73-76
26775591-4	2016	Here we described the emergence of an ALK F1245C mutation in an advanced ALK+ NSCLC patient (EML4-ALK variant 3a/b) who developed slow disease progression after a durable response to crizotinib.	Crizotinib	183-193	EMAP like 4	Homo sapiens	93-97
26775591-4	2016	Here we described the emergence of an ALK F1245C mutation in an advanced ALK+ NSCLC patient (EML4-ALK variant 3a/b) who developed slow disease progression after a durable response to crizotinib.	Crizotinib	183-193	ALK receptor tyrosine kinase	Homo sapiens	73-76
26775591-6	2016	This is the first patient report that ALK F1245C is an acquired resistance mutation to crizotinib that can be overcome by ceritinib.	Crizotinib	87-97	ALK receptor tyrosine kinase	Homo sapiens	38-41
26786851-0	2016	Novel ALK inhibitor AZD3463 inhibits neuroblastoma growth by overcoming crizotinib resistance and inducing apoptosis.	Crizotinib	72-82	anaplastic lymphoma kinase	Mus musculus	6-9
26958511-0	2016	Metachronous primary uterine cancer surgically resected during Crizotinib treatment in a ALK-rearranged advanced lung adenocarcinoma.	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	89-92
26958511-2	2016	Patients harboring ALK rearrangements show very favourable outcomes if treated with targeted agents, among which crizotinib is the first and best studied.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	19-22
26958511-3	2016	Crizotinib, an oral small-molecule tyrosine kinase inhibitor of ALK, MET, and ROS1 kinases, is a very active and well tolerated drug.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	64-67
26958511-3	2016	Crizotinib, an oral small-molecule tyrosine kinase inhibitor of ALK, MET, and ROS1 kinases, is a very active and well tolerated drug.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	78-82
26786851-3	2016	Crizotinib, a first-line therapy in the treatment of advanced non-small cell lung cancer (NSCLC) harboring ALK rearrangements, demonstrates striking efficacy against ALK-rearranged NB.	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	107-110
26786851-3	2016	Crizotinib, a first-line therapy in the treatment of advanced non-small cell lung cancer (NSCLC) harboring ALK rearrangements, demonstrates striking efficacy against ALK-rearranged NB.	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	166-169
26786851-4	2016	However, crizotinib fails to effectively inhibit the activity of ALK when activating mutations are present within its kinase domain, as with the F1174L mutation.	Crizotinib	9-19	anaplastic lymphoma kinase	Mus musculus	65-68
26811689-0	2016	Patients harboring EGFR mutation after primary resistance to crizotinib and response to EGFR-tyrosine kinase inhibitor.	Crizotinib	61-71	epidermal growth factor receptor	Homo sapiens	19-23
26933419-0	2016	Successful Management of Crizotinib-Induced Neutropenia in a Patient with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Case Report.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	74-100
26933419-1	2016	Crizotinib, the first clinically available inhibitor of anaplastic lymphoma kinase (ALK) gene rearrangement, is generally well tolerated.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	56-82
26933419-1	2016	Crizotinib, the first clinically available inhibitor of anaplastic lymphoma kinase (ALK) gene rearrangement, is generally well tolerated.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	84-87
26933419-5	2016	In this report, the successful management of crizotinib-induced neutropenia by dose reduction of crizotinib in a patient with ALK-positive non-small cell lung cancer is described.	Crizotinib	45-55	ALK receptor tyrosine kinase	Homo sapiens	126-129
26933419-5	2016	In this report, the successful management of crizotinib-induced neutropenia by dose reduction of crizotinib in a patient with ALK-positive non-small cell lung cancer is described.	Crizotinib	97-107	ALK receptor tyrosine kinase	Homo sapiens	126-129
26811689-4	2016	We present a case of harboring exon 19 deletion in epidermal growth factor receptor in ALK rearranged lung adenocarcinoma, who experienced a partial tumor response to icotinib after failure with crizotinib therapy and chemotherapy.	Crizotinib	195-205	epidermal growth factor receptor	Homo sapiens	51-83
26811689-4	2016	We present a case of harboring exon 19 deletion in epidermal growth factor receptor in ALK rearranged lung adenocarcinoma, who experienced a partial tumor response to icotinib after failure with crizotinib therapy and chemotherapy.	Crizotinib	195-205	ALK receptor tyrosine kinase	Homo sapiens	87-90
26544515-8	2016	In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK- platelets (hazard ratio, 3.5; P = 0.02).	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	167-170
26698910-0	2016	Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F.	Crizotinib	19-29	ALK receptor tyrosine kinase	Homo sapiens	48-51
26698910-1	2016	In a patient who had metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK kinase domain.	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	32-58
26698910-1	2016	In a patient who had metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK kinase domain.	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	60-63
26698910-1	2016	In a patient who had metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK kinase domain.	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	153-156
26736010-0	2016	Abrupt Relapse of ALK-Positive Lymphoma after Discontinuation of Crizotinib.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	18-21
27009821-1	2016	BACKGROUND AND OBJECTIVE: Crizotinib was developed in recent years based on targets of anaplastic lymphoma kinase (ALK) fusion genes.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	87-113
27009821-1	2016	BACKGROUND AND OBJECTIVE: Crizotinib was developed in recent years based on targets of anaplastic lymphoma kinase (ALK) fusion genes.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	115-118
27009821-2	2016	The aim of this study is to explore the efficacy of crizotinib in treatment of non-small cell lung cancer (NSCLC) with ALK/ROS1 rearrangement.	Crizotinib	52-62	ALK receptor tyrosine kinase	Homo sapiens	119-122
27009821-2	2016	The aim of this study is to explore the efficacy of crizotinib in treatment of non-small cell lung cancer (NSCLC) with ALK/ROS1 rearrangement.	Crizotinib	52-62	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	123-127
27009821-12	2016	CONCLUSION: The clinical features, efficacy, and adverse events of crizotinib in the treatment of the 40 patients with ALK/ROS1-positive NSCLC are similar to the data from the previous reports.	Crizotinib	67-77	ALK receptor tyrosine kinase	Homo sapiens	119-122
27009821-12	2016	CONCLUSION: The clinical features, efficacy, and adverse events of crizotinib in the treatment of the 40 patients with ALK/ROS1-positive NSCLC are similar to the data from the previous reports.	Crizotinib	67-77	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	123-127
26544515-9	2016	Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression.	Crizotinib	106-116	EMAP like 4	Homo sapiens	14-18
26544515-9	2016	Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression.	Crizotinib	106-116	ALK receptor tyrosine kinase	Homo sapiens	19-22
26775573-7	2016	Crizotinib is a new therapeutic standard in ALK translocated NSCLC in second line.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	44-47
26667344-2	2016	A multi-targeted ALK/ROS1/MET inhibitor, crizotinib, targeting this activated tyrosine kinase has led to significant clinical benefit including tumor shrinkage and prolonged survival without disease progression and has been approved by US FDA since 2011 for the treatment of advanced ALK-rearranged NSCLC (Ou et al.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	17-20
26667344-2	2016	A multi-targeted ALK/ROS1/MET inhibitor, crizotinib, targeting this activated tyrosine kinase has led to significant clinical benefit including tumor shrinkage and prolonged survival without disease progression and has been approved by US FDA since 2011 for the treatment of advanced ALK-rearranged NSCLC (Ou et al.	Crizotinib	41-51	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	21-25
26667344-2	2016	A multi-targeted ALK/ROS1/MET inhibitor, crizotinib, targeting this activated tyrosine kinase has led to significant clinical benefit including tumor shrinkage and prolonged survival without disease progression and has been approved by US FDA since 2011 for the treatment of advanced ALK-rearranged NSCLC (Ou et al.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	284-287
26703797-3	2016	Oncologists are requesting testing for ROS1 translocations which predict susceptibility to crizotinib, already approved for ALK positive lung cancers.	Crizotinib	91-101	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	39-43
26703797-3	2016	Oncologists are requesting testing for ROS1 translocations which predict susceptibility to crizotinib, already approved for ALK positive lung cancers.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	124-127
26775573-8	2016	Ceritinib is a 2nd generation ALK inhibitor which received a European marketing authorization for up to treatment of ALK translocated NSCLC after progression with crizotinib.	Crizotinib	163-173	ALK receptor tyrosine kinase	Homo sapiens	117-120
26554404-0	2016	The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma.	Crizotinib	67-77	ALK receptor tyrosine kinase	Homo sapiens	4-7
26749360-9	2016	Base case TICER for ROS1-guided crizotinib was $205,900/QALY.	Crizotinib	32-42	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	20-24
26544515-0	2016	Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer.	Crizotinib	103-113	EMAP like 4	Homo sapiens	11-15
26544515-0	2016	Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer.	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	16-19
26544515-1	2016	PURPOSE: Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib.	Crizotinib	88-98	EMAP like 4	Homo sapiens	47-51
26544515-1	2016	PURPOSE: Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib.	Crizotinib	88-98	ALK receptor tyrosine kinase	Homo sapiens	52-55
26544515-6	2016	In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival.	Crizotinib	81-91	EMAP like 4	Homo sapiens	32-36
26544515-6	2016	In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	37-40
26544515-6	2016	In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival.	Crizotinib	81-91	EMAP like 4	Homo sapiens	93-97
26544515-6	2016	In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	98-101
26544515-8	2016	In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK- platelets (hazard ratio, 3.5; P = 0.02).	Crizotinib	42-52	EMAP like 4	Homo sapiens	113-117
26544515-8	2016	In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK- platelets (hazard ratio, 3.5; P = 0.02).	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	118-121
26544515-8	2016	In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK- platelets (hazard ratio, 3.5; P = 0.02).	Crizotinib	42-52	EMAP like 4	Homo sapiens	162-166
27535394-4	2016	In patients with NSCLC with anaplastic lymphoma kinase (ALK) rearrangements, phase III trials of crizotinib have demonstrated superior efficacy compared to platinum-pemetrexed in the first-line setting and standard chemotherapy in the second-line setting.	Crizotinib	97-107	ALK receptor tyrosine kinase	Homo sapiens	28-54
27535394-4	2016	In patients with NSCLC with anaplastic lymphoma kinase (ALK) rearrangements, phase III trials of crizotinib have demonstrated superior efficacy compared to platinum-pemetrexed in the first-line setting and standard chemotherapy in the second-line setting.	Crizotinib	97-107	ALK receptor tyrosine kinase	Homo sapiens	56-59
27535394-5	2016	A second-generation ALK inhibitor, ceritinib, is available for patients who have progressed after or were intolerant of crizotinib.	Crizotinib	120-130	ALK receptor tyrosine kinase	Homo sapiens	20-23
27535394-6	2016	Crizotinib has also demonstrated activity on patients with ROS1 rearrangements, and BRAF inhibitors (dabrafenib, vemurafenib) have demonstrated activity in patients with NSCLC with BRAF V600E mutation.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	59-63
26554404-0	2016	The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma.	Crizotinib	67-77	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	8-12
26554404-1	2016	UNLABELLED: Neuroblastomas harboring activating point mutations in anaplastic lymphoma kinase (ALK) are differentially sensitive to the ALK inhibitor crizotinib, with certain mutations conferring intrinsic crizotinib resistance.	Crizotinib	150-160	ALK receptor tyrosine kinase	Homo sapiens	67-93
26554404-1	2016	UNLABELLED: Neuroblastomas harboring activating point mutations in anaplastic lymphoma kinase (ALK) are differentially sensitive to the ALK inhibitor crizotinib, with certain mutations conferring intrinsic crizotinib resistance.	Crizotinib	150-160	ALK receptor tyrosine kinase	Homo sapiens	95-98
26554404-1	2016	UNLABELLED: Neuroblastomas harboring activating point mutations in anaplastic lymphoma kinase (ALK) are differentially sensitive to the ALK inhibitor crizotinib, with certain mutations conferring intrinsic crizotinib resistance.	Crizotinib	150-160	ALK receptor tyrosine kinase	Homo sapiens	136-139
26554404-1	2016	UNLABELLED: Neuroblastomas harboring activating point mutations in anaplastic lymphoma kinase (ALK) are differentially sensitive to the ALK inhibitor crizotinib, with certain mutations conferring intrinsic crizotinib resistance.	Crizotinib	206-216	ALK receptor tyrosine kinase	Homo sapiens	67-93
26381283-12	2016	The 2 EGFR-mutant DP patients demonstrated a better response to crizotinib compared with erlotinib.	Crizotinib	64-74	epidermal growth factor receptor	Homo sapiens	6-10
26554404-1	2016	UNLABELLED: Neuroblastomas harboring activating point mutations in anaplastic lymphoma kinase (ALK) are differentially sensitive to the ALK inhibitor crizotinib, with certain mutations conferring intrinsic crizotinib resistance.	Crizotinib	206-216	ALK receptor tyrosine kinase	Homo sapiens	95-98
26554404-1	2016	UNLABELLED: Neuroblastomas harboring activating point mutations in anaplastic lymphoma kinase (ALK) are differentially sensitive to the ALK inhibitor crizotinib, with certain mutations conferring intrinsic crizotinib resistance.	Crizotinib	206-216	ALK receptor tyrosine kinase	Homo sapiens	136-139
26554404-7	2016	SIGNIFICANCE: The next-generation ALK/ROS1 inhibitor PF-06463922 exerts unparalleled activity in ALK-driven neuroblastoma models with primary crizotinib resistance.	Crizotinib	142-152	ALK receptor tyrosine kinase	Homo sapiens	34-37
26554404-7	2016	SIGNIFICANCE: The next-generation ALK/ROS1 inhibitor PF-06463922 exerts unparalleled activity in ALK-driven neuroblastoma models with primary crizotinib resistance.	Crizotinib	142-152	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	38-42
26381283-13	2016	The 2 KRAS-mutant DP patients experienced opposite responses to crizotinib.	Crizotinib	64-74	KRAS proto-oncogene, GTPase	Homo sapiens	6-10
26381283-15	2016	Patients with ALK/EGFR might benefit more from crizotinib compared with erlotinib administration, although the efficacy of TKIs in patients with ALK/KRAS remains unclear.	Crizotinib	47-57	ALK receptor tyrosine kinase	Homo sapiens	14-17
26381283-15	2016	Patients with ALK/EGFR might benefit more from crizotinib compared with erlotinib administration, although the efficacy of TKIs in patients with ALK/KRAS remains unclear.	Crizotinib	47-57	epidermal growth factor receptor	Homo sapiens	18-22
26582431-3	2016	Crizotinib is now recognized as the standard of care in ALK-positive NSCLC due to the positive results of recently published trials.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	56-59
27138017-0	2016	Resistance to Crizotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) with ALK Rearrangement: Mechanisms, Treatment Strategies and New Targeted Therapies.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	77-80
27138017-2	2016	Crizotinib is the first-in-class TKI approved as front-line or salvage therapy in advanced ALK-rearranged NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	91-94
27138017-5	2016	Novel second-generation ALK inhibitors are currently in clinical development with promising results in ALK-rearranged NSCLC, as well as in crizotinib-resistant patients.	Crizotinib	139-149	ALK receptor tyrosine kinase	Homo sapiens	24-27
27138017-8	2016	This review aims to discuss on strategy overcoming crizotinib-resistance starting from molecular mechanisms of resistance until novel ALK kinase inhibitors in ALK-rearranged NSCLC patients.	Crizotinib	51-61	ALK receptor tyrosine kinase	Homo sapiens	134-137
27138017-8	2016	This review aims to discuss on strategy overcoming crizotinib-resistance starting from molecular mechanisms of resistance until novel ALK kinase inhibitors in ALK-rearranged NSCLC patients.	Crizotinib	51-61	ALK receptor tyrosine kinase	Homo sapiens	159-162
27803410-1	2016	This is the first report in which crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, reduced an atypical carcinoid tumor with ALK rearrangement.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	49-75
26654422-0	2016	Overcoming crizotinib resistance in ALK-rearranged NSCLC with the second-generation ALK-inhibitor ceritinib.	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	36-39
26654422-0	2016	Overcoming crizotinib resistance in ALK-rearranged NSCLC with the second-generation ALK-inhibitor ceritinib.	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	84-87
26654422-2	2016	Treatment with the ALK inhibitor crizotinib is more effective than standard chemotherapy.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	19-22
26654422-4	2016	Ceritinib is the first second-generation ALK inhibitor approved for treatment of crizotinib-resistant NSCLC.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	41-44
26654422-5	2016	Ceritinib inhibits two of the most common ALK-mutants that confer resistance to crizotinib: L1196 M and G1269A.	Crizotinib	80-90	ALK receptor tyrosine kinase	Homo sapiens	42-45
26654422-6	2016	Cells with ALK expression are more sensitive to ceritinib than crizotinib (IC50 25 nM vs. 150 nM, respectively).	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	11-14
26654422-7	2016	Alternative second-generation ALK inhibitors such as Alectinib, Brigatinib and PF-06463922 are currently in development, each affecting different crizotinib-resistant ALK target mutations.	Crizotinib	146-156	ALK receptor tyrosine kinase	Homo sapiens	30-33
26654422-7	2016	Alternative second-generation ALK inhibitors such as Alectinib, Brigatinib and PF-06463922 are currently in development, each affecting different crizotinib-resistant ALK target mutations.	Crizotinib	146-156	ALK receptor tyrosine kinase	Homo sapiens	167-170
26585927-0	2016	Quantification of Anaplastic Lymphoma Kinase Protein Expression in Non-Small Cell Lung Cancer Tissues from Patients Treated with Crizotinib.	Crizotinib	129-139	ALK receptor tyrosine kinase	Homo sapiens	18-44
26585927-1	2016	BACKGROUND: Crizotinib has antitumor activity in ALK (anaplastic lymphoma receptor tyrosine kinase)-rearranged non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	49-52
26585927-1	2016	BACKGROUND: Crizotinib has antitumor activity in ALK (anaplastic lymphoma receptor tyrosine kinase)-rearranged non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	54-98
26585927-8	2016	Absolute ALK concentrations correlated with clinical response in 5 of 8 patients treated with crizotinib.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	9-12
26585927-12	2016	CONCLUSIONS: ALK concentrations measured by SRM correlate with crizotinib response in NSCLC patients.	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	13-16
26618223-2	2016	Two small molecule inhibitors of ALK, crizotinib and ceritinib, have been recently approved for the treatment of metastatic non-small-cell lung cancer, with marked improvement of progression-free survival of patients.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	33-36
26709645-2	2016	Few years ago crizotinib, an inhibitor of the receptor tyrosine kinases c-Met and ALK, demonstrated its activity in ALK positive non-small-cell lung cancer and other tumors with excellent toxicity profile.	Crizotinib	14-24	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	72-77
26709645-2	2016	Few years ago crizotinib, an inhibitor of the receptor tyrosine kinases c-Met and ALK, demonstrated its activity in ALK positive non-small-cell lung cancer and other tumors with excellent toxicity profile.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	82-85
26709645-2	2016	Few years ago crizotinib, an inhibitor of the receptor tyrosine kinases c-Met and ALK, demonstrated its activity in ALK positive non-small-cell lung cancer and other tumors with excellent toxicity profile.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	116-119
26935372-0	2016	Promising Effect of Crizotinib on Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer in an Elderly Patient with a Poor Performance Status: A Case Report and Literature Review.	Crizotinib	20-30	ALK receptor tyrosine kinase	Homo sapiens	34-60
26935372-0	2016	Promising Effect of Crizotinib on Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer in an Elderly Patient with a Poor Performance Status: A Case Report and Literature Review.	Crizotinib	20-30	ALK receptor tyrosine kinase	Homo sapiens	62-65
26935372-1	2016	Crizotinib is highly effective for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	35-61
26935372-1	2016	Crizotinib is highly effective for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	63-66
26935372-6	2016	Our results indicate that crizotinib could be an important choice when treating elderly patients with ALK-positive NSCLC with poor PS.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	102-105
27803410-1	2016	This is the first report in which crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, reduced an atypical carcinoid tumor with ALK rearrangement.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	77-80
27803410-1	2016	This is the first report in which crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, reduced an atypical carcinoid tumor with ALK rearrangement.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	134-137
26879065-0	2016	[Successful Therapy of Czech Patients with ROS1 Translocation by Crizotinib].	Crizotinib	65-75	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	43-47
26464158-2	2016	Many acquired resistant mutations to the anaplastic lymphoma kinase (ALK) gene have been identified during treatment of ALK-rearranged non-small cell lung cancer (NSCLC) patients with crizotinib, ceritinib, and alectinib.	Crizotinib	184-194	ALK receptor tyrosine kinase	Homo sapiens	41-67
26603857-0	2016	ALK-rearranged squamous cell lung carcinoma responding to crizotinib: A missing link in the field of non-small cell lung cancer?	Crizotinib	58-68	ALK receptor tyrosine kinase	Homo sapiens	0-3
26263240-8	2016	Despite the fact that crizotinib, a first-generation ALK inhibitor, is initially effective in dealing with non-small-cell lung cancer and its metastases, resistance to it seems to develop on a regular basis.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	53-56
26753004-1	2016	The treatment of patients with advanced non-small cell lung cancer (NSCLC) harbouring chromosomal rearrangements of ALK (anaplastic lymphoma kinase) was revolutionized by crizotinib, a small molecule inhibitor of ALK, ROS1 and MET.	Crizotinib	171-181	ALK receptor tyrosine kinase	Homo sapiens	116-119
26753004-1	2016	The treatment of patients with advanced non-small cell lung cancer (NSCLC) harbouring chromosomal rearrangements of ALK (anaplastic lymphoma kinase) was revolutionized by crizotinib, a small molecule inhibitor of ALK, ROS1 and MET.	Crizotinib	171-181	ALK receptor tyrosine kinase	Homo sapiens	121-147
26753004-1	2016	The treatment of patients with advanced non-small cell lung cancer (NSCLC) harbouring chromosomal rearrangements of ALK (anaplastic lymphoma kinase) was revolutionized by crizotinib, a small molecule inhibitor of ALK, ROS1 and MET.	Crizotinib	171-181	ALK receptor tyrosine kinase	Homo sapiens	213-216
26753004-1	2016	The treatment of patients with advanced non-small cell lung cancer (NSCLC) harbouring chromosomal rearrangements of ALK (anaplastic lymphoma kinase) was revolutionized by crizotinib, a small molecule inhibitor of ALK, ROS1 and MET.	Crizotinib	171-181	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	218-222
26753004-3	2016	Many of them had been reported even before its approval leading to the rapid development of second-generation ALK inhibitors for crizotinib-resistant NSCLC.	Crizotinib	129-139	ALK receptor tyrosine kinase	Homo sapiens	110-113
26816533-0	2016	Crizotinib versus platinum-based double-agent chemotherapy as the first line treatment in advanced anaplastic lymphoma kinase-positive lung adenocarcinoma.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	99-125
26816533-1	2016	BACKGROUND: To explore the efficacy and safety of crizotinib versus platinum-based double agent chemotherapy as the first-line treatment in patients with advanced anaplastic lymphoma kinase (ALK)-positive lung adenocarcinoma.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	191-194
26816533-11	2016	CONCLUSION: As a first-line treatment, crizotinib was superior to platinum-based double chemotherapy in patients with previously untreated advanced ALK-positive lung adenocarcinoma.	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	148-151
26531163-4	2015	The selective c-MET inhibitor, PF-2341066, can induce PEL apoptosis through cell cycle arrest and DNA damage, and suppress tumor progression in a xenograft murine model.	Crizotinib	31-41	met proto-oncogene	Mus musculus	14-19
27141355-13	2016	Anti-PD-1/PD-L1 antibodies could be an optional therapy for crizotinib sensitive, especially crizotinib resistant NSCLC patients with ALK fusion gene.	Crizotinib	60-70	CD274 molecule	Homo sapiens	10-15
27141355-13	2016	Anti-PD-1/PD-L1 antibodies could be an optional therapy for crizotinib sensitive, especially crizotinib resistant NSCLC patients with ALK fusion gene.	Crizotinib	93-103	CD274 molecule	Homo sapiens	10-15
27141355-13	2016	Anti-PD-1/PD-L1 antibodies could be an optional therapy for crizotinib sensitive, especially crizotinib resistant NSCLC patients with ALK fusion gene.	Crizotinib	93-103	ALK receptor tyrosine kinase	Homo sapiens	134-137
26677850-0	2015	Influence of Chirality of Crizotinib on Its MTH1 Protein Inhibitory Activity: Insight from Molecular Dynamics Simulations and Binding Free Energy Calculations.	Crizotinib	26-36	nudix hydrolase 1	Homo sapiens	44-48
26677850-1	2015	As a promising target for the treatment of lung cancer, the MutT Homolog 1 (MTH1) protein can be inhibited by crizotinib.	Crizotinib	110-120	nudix hydrolase 1	Homo sapiens	60-74
26677850-1	2015	As a promising target for the treatment of lung cancer, the MutT Homolog 1 (MTH1) protein can be inhibited by crizotinib.	Crizotinib	110-120	nudix hydrolase 1	Homo sapiens	76-80
26677850-2	2015	A recent work shows that the inhibitory potency of (S)-crizotinib against MTH1 is about 20 times over that of (R)-crizotinib.	Crizotinib	51-65	nudix hydrolase 1	Homo sapiens	74-78
26677850-4	2015	In this study, molecular dynamics (MD) simulations and free energy calculations were used to elucidate the mechanism about the effect of chirality of crizotinib on the inhibitory activity against MTH1.	Crizotinib	150-160	nudix hydrolase 1	Homo sapiens	196-200
26677850-7	2015	The binding free energy decomposition analysis illustrated that residues Tyr7, Phe27, Phe72 and Trp117 were important for the selective binding of (S)-crizotinib to MTH1.	Crizotinib	147-161	nudix hydrolase 1	Homo sapiens	165-169
26677850-8	2015	The adaptive biasing force (ABF) method was further employed to elucidate the unbinding process of (S)-crizotinib and (R)-crizotinib from the binding pocket of MTH1.	Crizotinib	99-113	nudix hydrolase 1	Homo sapiens	160-164
26677850-8	2015	The adaptive biasing force (ABF) method was further employed to elucidate the unbinding process of (S)-crizotinib and (R)-crizotinib from the binding pocket of MTH1.	Crizotinib	118-132	nudix hydrolase 1	Homo sapiens	160-164
26677850-10	2015	The results from our study can reveal the details about the effect of chirality on the inhibition activity of crizotinib to MTH1 and provide valuable information for the design of more potent inhibitors.	Crizotinib	110-120	nudix hydrolase 1	Homo sapiens	124-128
26870817-2	2016	Crizotinib and ceritinib, a next-generation ALK tyrosine kinase inhibitor (TKI) active against crizotinib-refractory patients, are clinically available for the treatment of ALK-rearranged NSCLC patients, and multiple next-generation ALK-TKIs are currently under clinical evaluation.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	44-47
26870817-2	2016	Crizotinib and ceritinib, a next-generation ALK tyrosine kinase inhibitor (TKI) active against crizotinib-refractory patients, are clinically available for the treatment of ALK-rearranged NSCLC patients, and multiple next-generation ALK-TKIs are currently under clinical evaluation.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	173-176
26870817-2	2016	Crizotinib and ceritinib, a next-generation ALK tyrosine kinase inhibitor (TKI) active against crizotinib-refractory patients, are clinically available for the treatment of ALK-rearranged NSCLC patients, and multiple next-generation ALK-TKIs are currently under clinical evaluation.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	173-176
26870817-6	2016	P-gp exported ceritinib and its overexpression conferred ceritinib and crizotinib resistance, but not to PF-06463922 or alectinib, which are next-generation ALK inhibitors.	Crizotinib	71-81	phosphoglycolate phosphatase	Homo sapiens	0-4
26870817-8	2016	P-gp overexpression was identified in three out of 11 cases with in ALK-rearranged crizotinib or ceritinib resistant NSCLC patients.	Crizotinib	83-93	phosphoglycolate phosphatase	Homo sapiens	0-4
26870817-8	2016	P-gp overexpression was identified in three out of 11 cases with in ALK-rearranged crizotinib or ceritinib resistant NSCLC patients.	Crizotinib	83-93	ALK receptor tyrosine kinase	Homo sapiens	68-71
26870817-9	2016	Our study suggests that alectinib, PF-06463922, or P-gp inhibitor with ceritinib could overcome the ceritinib or crizotinib resistance mediated by P-gp overexpression.	Crizotinib	113-123	phosphoglycolate phosphatase	Homo sapiens	51-55
26870817-9	2016	Our study suggests that alectinib, PF-06463922, or P-gp inhibitor with ceritinib could overcome the ceritinib or crizotinib resistance mediated by P-gp overexpression.	Crizotinib	113-123	phosphoglycolate phosphatase	Homo sapiens	147-151
26568289-1	2015	The treatment of patients with advanced non-small-cell lung cancer harboring chromosomal rearrangements of anaplastic lymphoma kinase (ALK) has been revolutionized by the development of crizotinib, a small-molecule inhibitor of ALK, ROS1, and MET.	Crizotinib	186-196	ALK receptor tyrosine kinase	Homo sapiens	107-133
26568289-1	2015	The treatment of patients with advanced non-small-cell lung cancer harboring chromosomal rearrangements of anaplastic lymphoma kinase (ALK) has been revolutionized by the development of crizotinib, a small-molecule inhibitor of ALK, ROS1, and MET.	Crizotinib	186-196	ALK receptor tyrosine kinase	Homo sapiens	135-138
26568289-1	2015	The treatment of patients with advanced non-small-cell lung cancer harboring chromosomal rearrangements of anaplastic lymphoma kinase (ALK) has been revolutionized by the development of crizotinib, a small-molecule inhibitor of ALK, ROS1, and MET.	Crizotinib	186-196	ALK receptor tyrosine kinase	Homo sapiens	228-231
26568289-1	2015	The treatment of patients with advanced non-small-cell lung cancer harboring chromosomal rearrangements of anaplastic lymphoma kinase (ALK) has been revolutionized by the development of crizotinib, a small-molecule inhibitor of ALK, ROS1, and MET.	Crizotinib	186-196	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	233-237
26645582-8	2015	The growth of pleiotrophin-producing GL261 gliomas was inhibited by treatment with the ALK inhibitor crizotinib, the ALK inhibitor ceritinib, or the VEGF receptor inhibitor cediranib, whereas control GL261 tumors did not respond to either inhibitor.	Crizotinib	101-111	pleiotrophin	Homo sapiens	14-26
26645582-8	2015	The growth of pleiotrophin-producing GL261 gliomas was inhibited by treatment with the ALK inhibitor crizotinib, the ALK inhibitor ceritinib, or the VEGF receptor inhibitor cediranib, whereas control GL261 tumors did not respond to either inhibitor.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	87-90
26597476-1	2015	Around 4% of advanced non-small cell lung cancers (NSCLC) harbor a ALK rearrangement, with high sensitivity to ALK inhibitor as crizotinib.	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	67-70
26597476-1	2015	Around 4% of advanced non-small cell lung cancers (NSCLC) harbor a ALK rearrangement, with high sensitivity to ALK inhibitor as crizotinib.	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	111-114
26342831-1	2015	Anaplastic lymphoma kinase (ALK) has been identified to exert a potent transforming activity through its rearrangement in non-small cell lung cancer (NSCLC), and patients (pts) with ALK rearrangement can be treated more successfully with ALK inhibitors, such as crizotinib, alectinib, and ceritinib, than with chemotherapy.	Crizotinib	262-272	ALK receptor tyrosine kinase	Homo sapiens	0-26
26342831-1	2015	Anaplastic lymphoma kinase (ALK) has been identified to exert a potent transforming activity through its rearrangement in non-small cell lung cancer (NSCLC), and patients (pts) with ALK rearrangement can be treated more successfully with ALK inhibitors, such as crizotinib, alectinib, and ceritinib, than with chemotherapy.	Crizotinib	262-272	ALK receptor tyrosine kinase	Homo sapiens	28-31
26342831-1	2015	Anaplastic lymphoma kinase (ALK) has been identified to exert a potent transforming activity through its rearrangement in non-small cell lung cancer (NSCLC), and patients (pts) with ALK rearrangement can be treated more successfully with ALK inhibitors, such as crizotinib, alectinib, and ceritinib, than with chemotherapy.	Crizotinib	262-272	ALK receptor tyrosine kinase	Homo sapiens	182-185
26342831-1	2015	Anaplastic lymphoma kinase (ALK) has been identified to exert a potent transforming activity through its rearrangement in non-small cell lung cancer (NSCLC), and patients (pts) with ALK rearrangement can be treated more successfully with ALK inhibitors, such as crizotinib, alectinib, and ceritinib, than with chemotherapy.	Crizotinib	262-272	ALK receptor tyrosine kinase	Homo sapiens	182-185
26342831-5	2015	Although the efficacy of crizotinib for the CNS lesions remains controversial, a recent retrospective investigation of ALK+ pts with BM enrolled in PROFILE 1005 and PROFILE 1007 demonstrated that crizotinib is associated with a high disease control rate for BM.	Crizotinib	196-206	ALK receptor tyrosine kinase	Homo sapiens	119-122
26648752-0	2015	Synergistic Effects of Crizotinib and Temozolomide in Experimental FIG-ROS1 Fusion-Positive Glioblastoma.	Crizotinib	23-33	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	71-75
26648752-8	2015	Our in vitro and ex vivo models promisingly demonstrated that treatments with crizotinib (PF-02341066: dual ALK/c-Met inhibitor) and temozolomide in combination induced synergistic antitumor activity on FIG-ROS1-positive GB cells.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	108-111
26648752-8	2015	Our in vitro and ex vivo models promisingly demonstrated that treatments with crizotinib (PF-02341066: dual ALK/c-Met inhibitor) and temozolomide in combination induced synergistic antitumor activity on FIG-ROS1-positive GB cells.	Crizotinib	78-88	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	112-117
26648752-8	2015	Our in vitro and ex vivo models promisingly demonstrated that treatments with crizotinib (PF-02341066: dual ALK/c-Met inhibitor) and temozolomide in combination induced synergistic antitumor activity on FIG-ROS1-positive GB cells.	Crizotinib	78-88	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	207-211
26381275-1	2015	PURPOSE: To investigate the potential effects of strong CYP3A inhibitor ketoconazole and strong CYP3A inducer rifampin on the pharmacokinetics of crizotinib in human.	Crizotinib	146-156	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	56-61
26381275-1	2015	PURPOSE: To investigate the potential effects of strong CYP3A inhibitor ketoconazole and strong CYP3A inducer rifampin on the pharmacokinetics of crizotinib in human.	Crizotinib	146-156	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	96-101
26381275-5	2015	RESULTS: Co-administration of a single 150-mg oral dose of crizotinib with the strong CYP3A inhibitor ketoconazole resulted in an area under the plasma-concentration curve extrapolated to infinity (AUC0-inf) 3.2-fold that for crizotinib alone.	Crizotinib	59-69	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	86-91
26381275-5	2015	RESULTS: Co-administration of a single 150-mg oral dose of crizotinib with the strong CYP3A inhibitor ketoconazole resulted in an area under the plasma-concentration curve extrapolated to infinity (AUC0-inf) 3.2-fold that for crizotinib alone.	Crizotinib	226-236	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	86-91
26381275-6	2015	Co-administration of a single 250-mg crizotinib dose with the strong CYP3A inducer rifampin caused an 82 % decrease in crizotinib AUC0-inf.	Crizotinib	37-47	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	69-74
26381275-6	2015	Co-administration of a single 250-mg crizotinib dose with the strong CYP3A inducer rifampin caused an 82 % decrease in crizotinib AUC0-inf.	Crizotinib	119-129	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	69-74
26381275-8	2015	CONCLUSIONS: These findings suggest that CYP3A plays an important role in the metabolism of both crizotinib and PF-06260182, with the extent of this role being greater for PF-06260182.	Crizotinib	97-107	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	41-46
26603857-4	2016	We intend to report a rare case of ALK-rearranged lung squamous cell carcinoma with response to crizotinib therapy.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	35-38
26464158-2	2016	Many acquired resistant mutations to the anaplastic lymphoma kinase (ALK) gene have been identified during treatment of ALK-rearranged non-small cell lung cancer (NSCLC) patients with crizotinib, ceritinib, and alectinib.	Crizotinib	184-194	ALK receptor tyrosine kinase	Homo sapiens	69-72
26464158-2	2016	Many acquired resistant mutations to the anaplastic lymphoma kinase (ALK) gene have been identified during treatment of ALK-rearranged non-small cell lung cancer (NSCLC) patients with crizotinib, ceritinib, and alectinib.	Crizotinib	184-194	ALK receptor tyrosine kinase	Homo sapiens	120-123
26464158-4	2016	We described a patient who developed an acquired ALK F1174V resistant mutation on progression from crizotinib that responded to alectinib for 18 months but then developed an acquired ALK I1171S mutation to alectinib.	Crizotinib	99-109	ALK receptor tyrosine kinase	Homo sapiens	49-52
26464158-4	2016	We described a patient who developed an acquired ALK F1174V resistant mutation on progression from crizotinib that responded to alectinib for 18 months but then developed an acquired ALK I1171S mutation to alectinib.	Crizotinib	99-109	ALK receptor tyrosine kinase	Homo sapiens	183-186
26452431-1	2015	We herein report a case of a 46-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged stage IV lung adenocarcinoma who received the ALK inhibitor crizotinib as second-line therapy.	Crizotinib	156-166	ALK receptor tyrosine kinase	Homo sapiens	52-78
26452431-1	2015	We herein report a case of a 46-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged stage IV lung adenocarcinoma who received the ALK inhibitor crizotinib as second-line therapy.	Crizotinib	156-166	ALK receptor tyrosine kinase	Homo sapiens	80-83
26477969-1	2015	OBJECTIVES: Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) screening is essential to its treatment such as crizotinib.	Crizotinib	139-149	ALK receptor tyrosine kinase	Homo sapiens	40-43
26452431-1	2015	We herein report a case of a 46-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged stage IV lung adenocarcinoma who received the ALK inhibitor crizotinib as second-line therapy.	Crizotinib	156-166	ALK receptor tyrosine kinase	Homo sapiens	142-145
26791794-0	2015	Responses to the multitargeted MET/ALK/ROS1 inhibitor crizotinib and co-occurring mutations in lung adenocarcinomas with MET amplification or MET exon 14 skipping mutation.	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	35-38
26519123-0	2015	First line crizotinib in anaplastic lymphoma kinase (ALK) rearranged squamous cell lung cancer.	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	25-51
26519123-0	2015	First line crizotinib in anaplastic lymphoma kinase (ALK) rearranged squamous cell lung cancer.	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	53-56
26519123-1	2015	Recently the superiority of Crizotinib to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC has been demonstrated.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	147-150
26519123-8	2015	To our knowledge, this the first report of first line treatment of full squamous ALK-positive NSCLC with crizotinib.	Crizotinib	105-115	ALK receptor tyrosine kinase	Homo sapiens	81-84
26791794-0	2015	Responses to the multitargeted MET/ALK/ROS1 inhibitor crizotinib and co-occurring mutations in lung adenocarcinomas with MET amplification or MET exon 14 skipping mutation.	Crizotinib	54-64	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	39-43
26791794-3	2015	METHODS: We analyzed cases with lung adenocarcinomas for representative genomic aberrations, evaluated the response to the multitargeted MET/ALK/ROS1 crizotinib TKI in cases with MET aberrations and profiled lung cancer cell lines with the aforementioned genomic changes.	Crizotinib	150-160	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	145-149
26791794-4	2015	RESULTS: Lung cancer cell lines with ALK rearrangement, ROS1 rearrangement or MET amplification had expected in vitro responses to crizotinib and the ALK/ROS1 TKI ceritinib.	Crizotinib	131-141	ALK receptor tyrosine kinase	Homo sapiens	37-40
26791794-4	2015	RESULTS: Lung cancer cell lines with ALK rearrangement, ROS1 rearrangement or MET amplification had expected in vitro responses to crizotinib and the ALK/ROS1 TKI ceritinib.	Crizotinib	131-141	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	56-60
26791794-7	2015	Putative crizotinib-responsive somatic mutations (ALK rearrangements, ROS1 rearrangements, high level MET amplification or MET exon 14 skipping mutations) were present in 10% of lung adenocarcinomas analyzed at our service and in 9.5% of the TCGA lung adenocarcinoma database.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	50-53
26791794-7	2015	Putative crizotinib-responsive somatic mutations (ALK rearrangements, ROS1 rearrangements, high level MET amplification or MET exon 14 skipping mutations) were present in 10% of lung adenocarcinomas analyzed at our service and in 9.5% of the TCGA lung adenocarcinoma database.	Crizotinib	9-19	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	70-74
26791794-8	2015	One patient each whose advanced tumors harbored high level MET amplification with wild-type PIK3CA or MET exon 14 skipping mutation with PIK3CA-p.Glu542Lys had significant responses to crizotinib; suggesting that PIK3CA co-mutation did not affect clinical response.	Crizotinib	185-195	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	92-98
26791794-8	2015	One patient each whose advanced tumors harbored high level MET amplification with wild-type PIK3CA or MET exon 14 skipping mutation with PIK3CA-p.Glu542Lys had significant responses to crizotinib; suggesting that PIK3CA co-mutation did not affect clinical response.	Crizotinib	185-195	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	137-143
26791794-8	2015	One patient each whose advanced tumors harbored high level MET amplification with wild-type PIK3CA or MET exon 14 skipping mutation with PIK3CA-p.Glu542Lys had significant responses to crizotinib; suggesting that PIK3CA co-mutation did not affect clinical response.	Crizotinib	185-195	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	137-143
26788139-1	2015	Non-small-cell lung cancer (NSCLC) with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation is resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib, but responds to the ALK-TKI crizotinib.	Crizotinib	295-305	EMAP like 4	Homo sapiens	117-121
26788139-1	2015	Non-small-cell lung cancer (NSCLC) with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation is resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib, but responds to the ALK-TKI crizotinib.	Crizotinib	295-305	ALK receptor tyrosine kinase	Homo sapiens	122-125
26517679-2	2015	Although the inhibitor crizotinib, as it blocks the kinase activity of the resulting EML4-ALK fusion protein, displays remarkable initial responses, a fraction of NSCLC cases eventually become resistant to crizotinib by acquiring mutations in the ALK domain or activating bypass pathways via EGFR, KIT, or KRAS.	Crizotinib	23-33	EMAP like 4	Homo sapiens	85-89
26361725-1	2015	We aimed to clarify the roles of the multidrug transporters ABCB1 and ABCG2 in oral availability and brain accumulation of ceritinib, an oral anaplastic lymphoma kinase (ALK) inhibitor used to treat metastatic non-small cell lung cancer (NSCLC) after progression on crizotinib.	Crizotinib	266-276	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	60-65
26384345-0	2015	Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines.	Crizotinib	0-10	signal transducer and activator of transcription 3	Homo sapiens	55-60
26384345-3	2015	In this study, we found that crizotinib induced a high level of autophagy in lung cancer cells through inhibition of STAT3.	Crizotinib	29-39	signal transducer and activator of transcription 3	Homo sapiens	117-122
26384345-4	2015	Ectopic expression of wild-type or constitutive activated STAT3 significantly suppressed the effect of crizotinib on autophagy.	Crizotinib	103-113	signal transducer and activator of transcription 3	Homo sapiens	58-63
26384345-5	2015	Interestingly, crizotinib-mediated inhibition of STAT3 is in a step-wise manner.	Crizotinib	15-25	signal transducer and activator of transcription 3	Homo sapiens	49-54
26517679-2	2015	Although the inhibitor crizotinib, as it blocks the kinase activity of the resulting EML4-ALK fusion protein, displays remarkable initial responses, a fraction of NSCLC cases eventually become resistant to crizotinib by acquiring mutations in the ALK domain or activating bypass pathways via EGFR, KIT, or KRAS.	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	90-93
26384345-7	2015	Cell death induced by crizotinib was greatly enhanced after the inhibition of autophagy by the pharmacological inhibitors or shRNAs against Beclin-1.	Crizotinib	22-32	beclin 1	Homo sapiens	140-148
26517679-2	2015	Although the inhibitor crizotinib, as it blocks the kinase activity of the resulting EML4-ALK fusion protein, displays remarkable initial responses, a fraction of NSCLC cases eventually become resistant to crizotinib by acquiring mutations in the ALK domain or activating bypass pathways via EGFR, KIT, or KRAS.	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	247-250
26384345-9	2015	In conclusion, crizotinib can induce cytoprotective autophagy by suppression of STAT3 in lung cancer cells.	Crizotinib	15-25	signal transducer and activator of transcription 3	Homo sapiens	80-85
26517679-2	2015	Although the inhibitor crizotinib, as it blocks the kinase activity of the resulting EML4-ALK fusion protein, displays remarkable initial responses, a fraction of NSCLC cases eventually become resistant to crizotinib by acquiring mutations in the ALK domain or activating bypass pathways via EGFR, KIT, or KRAS.	Crizotinib	23-33	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	298-301
26517679-2	2015	Although the inhibitor crizotinib, as it blocks the kinase activity of the resulting EML4-ALK fusion protein, displays remarkable initial responses, a fraction of NSCLC cases eventually become resistant to crizotinib by acquiring mutations in the ALK domain or activating bypass pathways via EGFR, KIT, or KRAS.	Crizotinib	23-33	KRAS proto-oncogene, GTPase	Homo sapiens	306-310
26517679-7	2015	Importantly, combinational treatment with rapamycin and crizotinib leads to synergistic anti-tumor effects on EML4-ALK+ NSCLC cells as well as on those resistant to crizotinib.	Crizotinib	56-66	EMAP like 4	Homo sapiens	110-114
26517679-7	2015	Importantly, combinational treatment with rapamycin and crizotinib leads to synergistic anti-tumor effects on EML4-ALK+ NSCLC cells as well as on those resistant to crizotinib.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	115-118
26504000-9	2015	Metastatic involvement of the CNS appears to be a relatively common complication in patients with ALK-positive NSCLC and the CNS represents a dominant site of progression in ALK-positive patients treated with the ALK TKI crizotinib.	Crizotinib	221-231	ALK receptor tyrosine kinase	Homo sapiens	174-177
26563356-0	2016	Evaluation of a Congenital Infantile Fibrosarcoma by Comprehensive Genomic Profiling Reveals an LMNA-NTRK1 Gene Fusion Responsive to Crizotinib.	Crizotinib	133-143	lamin A/C	Homo sapiens	96-100
26563356-0	2016	Evaluation of a Congenital Infantile Fibrosarcoma by Comprehensive Genomic Profiling Reveals an LMNA-NTRK1 Gene Fusion Responsive to Crizotinib.	Crizotinib	133-143	neurotrophic receptor tyrosine kinase 1	Homo sapiens	101-106
26504000-9	2015	Metastatic involvement of the CNS appears to be a relatively common complication in patients with ALK-positive NSCLC and the CNS represents a dominant site of progression in ALK-positive patients treated with the ALK TKI crizotinib.	Crizotinib	221-231	ALK receptor tyrosine kinase	Homo sapiens	174-177
26504000-10	2015	In addition, CNS progression on crizotinib contributes substantially to the high levels of morbidity and mortality observed among patients with ALK-rearrangements, a finding that is consistent with low CNS penetration of the drug.	Crizotinib	32-42	ALK receptor tyrosine kinase	Homo sapiens	144-147
26298289-5	2015	Just like the pyrotechnic flares that produce brilliant light when activated, the resulting AuNP flares@MSN (S-crizotinib) undergo a significant burst of red fluorescence enhancement upon MTH1 mRNA binding.	Crizotinib	111-121	nudix hydrolase 1	Homo sapiens	188-192
26551338-2	2015	Crizotinib is a tyrosine kinase inhibitor that has been shown to prolong progression-free survival in patients with advanced non-small cell lung cancer harboring ALK gene rearrangements.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	162-165
26823889-6	2015	After surgery the patient received chemotherapy with an anaplastic lymphoma kinase (ALK) inhibitor, crizotinib.	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	56-82
25847523-1	2015	AIMS: Accurate assessment of anaplastic lymphoma kinase (ALK) gene rearrangement in non-small-cell lung cancers (NSCLCs) is critical to identify patients who are likely to respond to crizotinib.	Crizotinib	183-193	ALK receptor tyrosine kinase	Homo sapiens	29-55
25847523-1	2015	AIMS: Accurate assessment of anaplastic lymphoma kinase (ALK) gene rearrangement in non-small-cell lung cancers (NSCLCs) is critical to identify patients who are likely to respond to crizotinib.	Crizotinib	183-193	ALK receptor tyrosine kinase	Homo sapiens	57-60
26823889-6	2015	After surgery the patient received chemotherapy with an anaplastic lymphoma kinase (ALK) inhibitor, crizotinib.	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	84-87
29750613-2	2015	Although crizotinib has proved effective in treating ALK-positive NSCLC, this agent penetrates the blood-brain barrier poorly and CNS progression is common.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	53-56
26352533-0	2015	EML4-ALK Fusion Detected by RT-PCR Confers Similar Response to Crizotinib as Detected by FISH in Patients with Advanced Non-Small-Cell Lung Cancer.	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	5-8
26352533-2	2015	The aim of this study was to investigate the response to crizotinib in patients of advanced non-small-cell lung cancer (NSCLC) with ALK rearrangements detected by RT-PCR.	Crizotinib	57-67	ALK receptor tyrosine kinase	Homo sapiens	132-135
26352533-4	2015	The utility of RT-PCR and fluorescence in situ hybridization (FISH) assay were compared in patients who were treated with crizotinib based on their positive ALK rearrangements.	Crizotinib	122-132	ALK receptor tyrosine kinase	Homo sapiens	157-160
26352533-9	2015	Interestingly, there were two patients responded to crizotinib had their ALK rearrangement detected by RT-PCR but not FISH.	Crizotinib	52-62	ALK receptor tyrosine kinase	Homo sapiens	73-76
26352533-10	2015	CONCLUSIONS: RT-PCR should be considered as an alternative/supplemental approach to detect ALK fusion oncogene in NSCLC patients who might benefit from crizotinib treatment.	Crizotinib	152-162	ALK receptor tyrosine kinase	Homo sapiens	91-94
26033699-1	2015	We report the case of a woman with an ALK positive lung adenocarcinoma, who developed bilateral complex renal cysts 17 months after the introduction of treatment with crizotinib.	Crizotinib	167-177	ALK receptor tyrosine kinase	Homo sapiens	38-41
26468446-5	2015	ALK-driven tumors can be treated with Crizotinib, an orally available dual ALK/MET inhibitor, currently approved for advanced ALK-positive NSCLCs.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	0-3
26995877-1	2015	Companion diagnostics (CoDx) will likely continue to rapidly increase in number and application to disease areas including solid tumors, for example EGFR for gefitinib and ALK fusion gene for crizotinib in non-small-cell lung cancer; KRAS against the use of cetuximab and panitumumab in colorectal cancer; HER2 for trastuzumab in breast cancer.	Crizotinib	192-202	epidermal growth factor receptor	Homo sapiens	149-153
26995877-1	2015	Companion diagnostics (CoDx) will likely continue to rapidly increase in number and application to disease areas including solid tumors, for example EGFR for gefitinib and ALK fusion gene for crizotinib in non-small-cell lung cancer; KRAS against the use of cetuximab and panitumumab in colorectal cancer; HER2 for trastuzumab in breast cancer.	Crizotinib	192-202	ALK receptor tyrosine kinase	Homo sapiens	172-175
27141364-7	2016	ALK knockdown or inhibition (crizotinib treatment) in H2228 cells downregulated PD-L1 expression.	Crizotinib	29-39	CD274 molecule	Homo sapiens	80-85
27141364-8	2016	Transfection of H23 cells with EML4-ALK enhanced PD-L1 expression, which was compromised by crizotinib treatment.	Crizotinib	92-102	EMAP like 4	Homo sapiens	31-35
27141364-8	2016	Transfection of H23 cells with EML4-ALK enhanced PD-L1 expression, which was compromised by crizotinib treatment.	Crizotinib	92-102	ALK receptor tyrosine kinase	Homo sapiens	36-39
27141364-8	2016	Transfection of H23 cells with EML4-ALK enhanced PD-L1 expression, which was compromised by crizotinib treatment.	Crizotinib	92-102	CD274 molecule	Homo sapiens	49-54
27141364-12	2016	Among patients with ALK-translocated pADC, strong PD-L1 expression was significantly associated with shorter progression-free (p = 0.001) and overall survival (p = 0.002) after crizotinib treatment.	Crizotinib	177-187	ALK receptor tyrosine kinase	Homo sapiens	20-23
27141364-12	2016	Among patients with ALK-translocated pADC, strong PD-L1 expression was significantly associated with shorter progression-free (p = 0.001) and overall survival (p = 0.002) after crizotinib treatment.	Crizotinib	177-187	CD274 molecule	Homo sapiens	50-55
26496080-7	2015	Crizotinib and canertinib both inhibited cell viability and phosphorylation of Akt and ERK1/2.	Crizotinib	0-10	AKT serine/threonine kinase 1	Homo sapiens	79-82
26496080-7	2015	Crizotinib and canertinib both inhibited cell viability and phosphorylation of Akt and ERK1/2.	Crizotinib	0-10	mitogen-activated protein kinase 3	Homo sapiens	87-93
26496080-10	2015	The HGF-induced bypass of canertinib was reversed by addition of crizotinib.	Crizotinib	65-75	hepatocyte growth factor	Homo sapiens	4-7
26483333-0	2015	[Clinical Efficacy of Crizotinib in Advanced ALK Positive  : Non-small Cell Lung Cancer].	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	45-48
26483333-1	2015	BACKGROUND: The aim of this study is to explore clinical efficacy of crizotinib in advanced anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer.	Crizotinib	69-79	ALK receptor tyrosine kinase	Homo sapiens	92-118
26483333-1	2015	BACKGROUND: The aim of this study is to explore clinical efficacy of crizotinib in advanced anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer.	Crizotinib	69-79	ALK receptor tyrosine kinase	Homo sapiens	120-123
26483333-12	2015	CONCLUSIONS: Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced ALK positive non-small cell lung cancer.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	107-110
26468446-5	2015	ALK-driven tumors can be treated with Crizotinib, an orally available dual ALK/MET inhibitor, currently approved for advanced ALK-positive NSCLCs.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	75-78
26468446-5	2015	ALK-driven tumors can be treated with Crizotinib, an orally available dual ALK/MET inhibitor, currently approved for advanced ALK-positive NSCLCs.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	75-78
26338968-0	2015	Targeting autophagy enhances the anti-tumoral action of crizotinib in ALK-positive anaplastic large cell lymphoma.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	70-73
26299615-2	2015	The ALK-inhibitor crizotinib has a limited activity against the various ALK mutations identified in NB patients.	Crizotinib	18-28	anaplastic lymphoma kinase	Mus musculus	4-7
26299615-2	2015	The ALK-inhibitor crizotinib has a limited activity against the various ALK mutations identified in NB patients.	Crizotinib	18-28	ALK receptor tyrosine kinase	Homo sapiens	72-75
26338968-4	2015	Crizotinib is the most advanced ALK tyrosine kinase inhibitor and is already used in clinics to treat ALK-associated cancers.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	32-35
26338968-4	2015	Crizotinib is the most advanced ALK tyrosine kinase inhibitor and is already used in clinics to treat ALK-associated cancers.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	102-105
26338968-7	2015	In this study, we investigated whether autophagy is activated in ALCL cells submitted to ALK inactivation (using crizotinib or ALK-targeting siRNA).	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	89-92
26338968-10	2015	Altogether, our results suggest that co-treatment with crizotinib and chloroquine (two drugs already used in clinics) could be beneficial for ALK-positive ALCL patients.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	142-145
26445453-0	2015	Crizotinib-induced antitumour activity in human alveolar rhabdomyosarcoma cells is not solely dependent on ALK and MET inhibition.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	107-110
26445453-3	2015	This observation suggests that crizotinib (PF-02341066), a kinase inhibitor against ALK and MET, may have a therapeutic role in RMS, although its antitumour activity in this malignancy has not yet been studied.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	84-87
26445453-3	2015	This observation suggests that crizotinib (PF-02341066), a kinase inhibitor against ALK and MET, may have a therapeutic role in RMS, although its antitumour activity in this malignancy has not yet been studied.	Crizotinib	43-54	ALK receptor tyrosine kinase	Homo sapiens	84-87
26445453-4	2015	METHODS: RH4 and RH30 alveolar RMS (ARMS) cell lines were treated with crizotinib and then assessed by using proliferation, viability, migration and colony formation assays.	Crizotinib	71-81	Rh blood group D antigen	Homo sapiens	9-12
26445453-6	2015	RESULTS: In vitro treatment with crizotinib inhibited ALK and MET proteins, as well as Insulin-like Growth Factor 1 Receptor (IGF1R), with a concomitant robust dephosphorylation of AKT and ERK, two downstream kinases involved in RMS cell proliferation and survival.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	54-57
26445453-6	2015	RESULTS: In vitro treatment with crizotinib inhibited ALK and MET proteins, as well as Insulin-like Growth Factor 1 Receptor (IGF1R), with a concomitant robust dephosphorylation of AKT and ERK, two downstream kinases involved in RMS cell proliferation and survival.	Crizotinib	33-43	insulin like growth factor 1 receptor	Homo sapiens	87-124
26445453-6	2015	RESULTS: In vitro treatment with crizotinib inhibited ALK and MET proteins, as well as Insulin-like Growth Factor 1 Receptor (IGF1R), with a concomitant robust dephosphorylation of AKT and ERK, two downstream kinases involved in RMS cell proliferation and survival.	Crizotinib	33-43	insulin like growth factor 1 receptor	Homo sapiens	126-131
23934135-10	2015	CONCLUSIONS: Because of cellular cross-talk between MET and IGF-1 signaling, elevated IGF-1 levels induced by crizotinib treatment may have implications for long-term drug efficacy.	Crizotinib	110-120	insulin like growth factor 1	Homo sapiens	60-65
26445453-6	2015	RESULTS: In vitro treatment with crizotinib inhibited ALK and MET proteins, as well as Insulin-like Growth Factor 1 Receptor (IGF1R), with a concomitant robust dephosphorylation of AKT and ERK, two downstream kinases involved in RMS cell proliferation and survival.	Crizotinib	33-43	AKT serine/threonine kinase 1	Homo sapiens	181-184
23934135-10	2015	CONCLUSIONS: Because of cellular cross-talk between MET and IGF-1 signaling, elevated IGF-1 levels induced by crizotinib treatment may have implications for long-term drug efficacy.	Crizotinib	110-120	insulin like growth factor 1	Homo sapiens	86-91
26445453-6	2015	RESULTS: In vitro treatment with crizotinib inhibited ALK and MET proteins, as well as Insulin-like Growth Factor 1 Receptor (IGF1R), with a concomitant robust dephosphorylation of AKT and ERK, two downstream kinases involved in RMS cell proliferation and survival.	Crizotinib	33-43	mitogen-activated protein kinase 1	Homo sapiens	189-192
26445453-7	2015	Exposure to crizotinib impaired cell growth, and accumulation at G2/M phase was attributed to an altered expression and activation of checkpoint regulators, such as Cyclin B1 and Cdc2.	Crizotinib	12-22	cyclin B1	Homo sapiens	165-174
26445453-7	2015	Exposure to crizotinib impaired cell growth, and accumulation at G2/M phase was attributed to an altered expression and activation of checkpoint regulators, such as Cyclin B1 and Cdc2.	Crizotinib	12-22	cyclin dependent kinase 1	Homo sapiens	179-183
26445453-8	2015	Crizotinib was able to induce apoptosis and autophagy in a dose-dependent manner, as shown by caspase-3 activation/PARP proteolytic cleavage down-regulation and by LC3 activation/p62 down-regulation, respectively.	Crizotinib	0-10	caspase 3	Homo sapiens	94-103
26445453-8	2015	Crizotinib was able to induce apoptosis and autophagy in a dose-dependent manner, as shown by caspase-3 activation/PARP proteolytic cleavage down-regulation and by LC3 activation/p62 down-regulation, respectively.	Crizotinib	0-10	collagen type XI alpha 2 chain	Homo sapiens	115-119
26445453-8	2015	Crizotinib was able to induce apoptosis and autophagy in a dose-dependent manner, as shown by caspase-3 activation/PARP proteolytic cleavage down-regulation and by LC3 activation/p62 down-regulation, respectively.	Crizotinib	0-10	microtubule associated protein 1 light chain 3 alpha	Homo sapiens	164-167
26445453-8	2015	Crizotinib was able to induce apoptosis and autophagy in a dose-dependent manner, as shown by caspase-3 activation/PARP proteolytic cleavage down-regulation and by LC3 activation/p62 down-regulation, respectively.	Crizotinib	0-10	nucleoporin 62	Homo sapiens	179-182
26445453-9	2015	The accumulation of reactive oxygen species (ROS) seemed to contribute to crizotinib effects in RH4 and RH30 cells.	Crizotinib	74-84	Rh blood group D antigen	Homo sapiens	96-99
26445453-10	2015	Moreover, crizotinib-treated RH4 and RH30 cells exhibited a decreased migratory/invasive capacity and clonogenic potential.	Crizotinib	10-20	Rh blood group D antigen	Homo sapiens	29-32
26318457-5	2015	A broad array of newer generation ALK inhibitors are in development that appear effective in the crizotinib-resistant setting including in patients with intracranial progression.	Crizotinib	97-107	ALK receptor tyrosine kinase	Homo sapiens	34-37
26629437-0	2015	Crizotinib as first line therapy for advanced ALK-positive non-small cell lung cancers.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	46-49
26180127-0	2015	Prediction of Drug-Drug Interactions with Crizotinib as the CYP3A Substrate Using a Physiologically Based Pharmacokinetic Model.	Crizotinib	42-52	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	60-65
26180127-1	2015	An orally available multiple tyrosine kinase inhibitor, crizotinib (Xalkori), is a CYP3A substrate, moderate time-dependent inhibitor, and weak inducer.	Crizotinib	56-66	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	83-88
26180127-8	2015	Overall, we believe that the crizotinib PBPK model developed, refined, and verified in the present study would adequately predict crizotinib oral exposures in other clinical studies, such as DDIs with weak/moderate CYP3A inhibitors/inducers and drug-disease interactions in patients with hepatic or renal impairment.	Crizotinib	29-39	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	215-220
25795305-15	2015	Our findings are of particular importance because crizotinib, a selective ALK inhibitor, has demonstrated effect in patients with lung cancer harboring ALK rearrangements.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	74-77
25795305-15	2015	Our findings are of particular importance because crizotinib, a selective ALK inhibitor, has demonstrated effect in patients with lung cancer harboring ALK rearrangements.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	152-155
26629439-0	2015	Moving molecularly directed therapies to the first-line in ALK-positive lung cancer: crizotinib is just the beginning.	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	59-62
26629439-5	2015	The phase III PROFILE 1014 represents the culmination of the rapid development of crizotinib and provides lessons for future generation ALK inhibitors and other molecularly directed therapies in NSCLC.	Crizotinib	82-92	ALK receptor tyrosine kinase	Homo sapiens	136-139
26813601-0	2015	[Efficacy of crizotinib for 28 cases of advanced ALK-positive non-small cell lung cancer].	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	49-52
26372962-2	2015	The phylogenetic proximity of the ROS1 and anaplastic lymphoma kinase (ALK) catalytic domains led to the clinical repurposing of the Food and Drug Administration (FDA)-approved ALK inhibitor crizotinib as a ROS1 inhibitor.	Crizotinib	191-201	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	34-38
26372962-2	2015	The phylogenetic proximity of the ROS1 and anaplastic lymphoma kinase (ALK) catalytic domains led to the clinical repurposing of the Food and Drug Administration (FDA)-approved ALK inhibitor crizotinib as a ROS1 inhibitor.	Crizotinib	191-201	ALK receptor tyrosine kinase	Homo sapiens	43-69
26372962-2	2015	The phylogenetic proximity of the ROS1 and anaplastic lymphoma kinase (ALK) catalytic domains led to the clinical repurposing of the Food and Drug Administration (FDA)-approved ALK inhibitor crizotinib as a ROS1 inhibitor.	Crizotinib	191-201	ALK receptor tyrosine kinase	Homo sapiens	71-74
26372962-2	2015	The phylogenetic proximity of the ROS1 and anaplastic lymphoma kinase (ALK) catalytic domains led to the clinical repurposing of the Food and Drug Administration (FDA)-approved ALK inhibitor crizotinib as a ROS1 inhibitor.	Crizotinib	191-201	ALK receptor tyrosine kinase	Homo sapiens	177-180
26372962-2	2015	The phylogenetic proximity of the ROS1 and anaplastic lymphoma kinase (ALK) catalytic domains led to the clinical repurposing of the Food and Drug Administration (FDA)-approved ALK inhibitor crizotinib as a ROS1 inhibitor.	Crizotinib	191-201	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	207-211
26372962-3	2015	Despite the antitumor activity of crizotinib observed in both ROS1- and ALK-rearranged NSCLC patients, resistance due to acquisition of ROS1 or ALK kinase domain mutations has been observed clinically, spurring the development of second-generation inhibitors.	Crizotinib	34-44	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	62-66
26372962-3	2015	Despite the antitumor activity of crizotinib observed in both ROS1- and ALK-rearranged NSCLC patients, resistance due to acquisition of ROS1 or ALK kinase domain mutations has been observed clinically, spurring the development of second-generation inhibitors.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	72-75
26813601-1	2015	OBJECTIVE: This study aims to evaluate the efficacy and safety of crizotinib for advanced ALK-positive non-small cell lung cancer (NSCLC) patients.	Crizotinib	66-76	ALK receptor tyrosine kinase	Homo sapiens	90-93
26813601-14	2015	CONCLUSIONS: Crizotinib is effective and tolerable in the treatment of advanced ALK-positive NSLCC.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	80-83
26622190-1	2015	The fusion of echinoderm microtubule-associated protein-like 4 with the anaplastic lymphoma kinase (EML4-ALK) is found in 3%-7% of non-small-cell lung cancer (NSCLC) cases and confers sensitivity to crizotinib, the first United States Food and Drug Administration (FDA)-approved ALK inhibitor drug.	Crizotinib	199-209	EMAP like 4	Homo sapiens	14-62
26622190-1	2015	The fusion of echinoderm microtubule-associated protein-like 4 with the anaplastic lymphoma kinase (EML4-ALK) is found in 3%-7% of non-small-cell lung cancer (NSCLC) cases and confers sensitivity to crizotinib, the first United States Food and Drug Administration (FDA)-approved ALK inhibitor drug.	Crizotinib	199-209	EMAP like 4	Homo sapiens	100-104
26622190-1	2015	The fusion of echinoderm microtubule-associated protein-like 4 with the anaplastic lymphoma kinase (EML4-ALK) is found in 3%-7% of non-small-cell lung cancer (NSCLC) cases and confers sensitivity to crizotinib, the first United States Food and Drug Administration (FDA)-approved ALK inhibitor drug.	Crizotinib	199-209	ALK receptor tyrosine kinase	Homo sapiens	105-108
26622190-1	2015	The fusion of echinoderm microtubule-associated protein-like 4 with the anaplastic lymphoma kinase (EML4-ALK) is found in 3%-7% of non-small-cell lung cancer (NSCLC) cases and confers sensitivity to crizotinib, the first United States Food and Drug Administration (FDA)-approved ALK inhibitor drug.	Crizotinib	199-209	ALK receptor tyrosine kinase	Homo sapiens	279-282
26622190-3	2015	Resistance may involve secondary gatekeeper mutations within the ALK gene interfering with crizotinib-ALK interactions, or compensatory activation of aberrant bypass signaling pathways.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	65-68
26622190-5	2015	Ceritinib, a second-generation ALK inhibitor, overcomes several crizotinib-resistant ALK mutations and has demonstrated efficacy against tumor growth in several in vitro and in vivo preclinical models of crizotinib resistance.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	85-88
26622190-6	2015	Notably, the dose-escalation Phase I ASCEND-1 trial has shown a marked activity of ceritinib in both crizotinib-naive and crizotinib-resistant ALK-rearranged lung cancer.	Crizotinib	122-132	ALK receptor tyrosine kinase	Homo sapiens	143-146
28210152-7	2015	Crizotinib was the first agent proven to be efficacious as first-line treatment for ALK-positive NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	84-87
26172300-10	2015	Growth of a tumor cell line derived from this EML4-ALK CRC patient was inhibited by ALK inhibitors crizotinib and entrectinib.	Crizotinib	99-109	EMAP like 4	Homo sapiens	46-50
26172300-10	2015	Growth of a tumor cell line derived from this EML4-ALK CRC patient was inhibited by ALK inhibitors crizotinib and entrectinib.	Crizotinib	99-109	ALK receptor tyrosine kinase	Homo sapiens	51-54
26172300-10	2015	Growth of a tumor cell line derived from this EML4-ALK CRC patient was inhibited by ALK inhibitors crizotinib and entrectinib.	Crizotinib	99-109	ALK receptor tyrosine kinase	Homo sapiens	84-87
28210152-10	2015	Hence, more potent, selective next-generation ALK inhibitors that are able to cross the blood-brain barrier have been developed for treatment against crizotinib-resistant ALK-positive NSCLC and are also currently being evaluated for first-line therapy as well.	Crizotinib	150-160	ALK receptor tyrosine kinase	Homo sapiens	46-49
28210152-10	2015	Hence, more potent, selective next-generation ALK inhibitors that are able to cross the blood-brain barrier have been developed for treatment against crizotinib-resistant ALK-positive NSCLC and are also currently being evaluated for first-line therapy as well.	Crizotinib	150-160	ALK receptor tyrosine kinase	Homo sapiens	171-174
26294238-1	2015	PURPOSE: Published data on the clinical efficacy, safety, dosage and administration, and costs of the anaplastic lymphoma kinase (ALK) inhibitors crizotinib and ceritinib in the treatment of non-small-cell lung cancer (NSCLC) are reviewed and compared.	Crizotinib	146-156	ALK receptor tyrosine kinase	Homo sapiens	102-128
26351314-1	2015	Crizotinib is a tyrosine kinase inhibitor that demonstrates a dramatic tumour response in patients with advanced non-small cell lung cancers harbouring anaplastic lymphoma kinase (ALK) rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	152-178
26351314-1	2015	Crizotinib is a tyrosine kinase inhibitor that demonstrates a dramatic tumour response in patients with advanced non-small cell lung cancers harbouring anaplastic lymphoma kinase (ALK) rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	180-183
26294238-1	2015	PURPOSE: Published data on the clinical efficacy, safety, dosage and administration, and costs of the anaplastic lymphoma kinase (ALK) inhibitors crizotinib and ceritinib in the treatment of non-small-cell lung cancer (NSCLC) are reviewed and compared.	Crizotinib	146-156	ALK receptor tyrosine kinase	Homo sapiens	130-133
26294238-3	2015	Crizotinib is an oral tyrosine kinase inhibitor approved in 2011 as a first-line therapy for patients with metastatic ALK mutation-driven NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	118-121
26294238-5	2015	The second-generation ALK inhibitor ceritinib was approved in 2014 for the treatment of ALK-mutated NSCLC in patients who are intolerant or develop resistance to crizotinib.	Crizotinib	162-172	ALK receptor tyrosine kinase	Homo sapiens	22-25
26294238-5	2015	The second-generation ALK inhibitor ceritinib was approved in 2014 for the treatment of ALK-mutated NSCLC in patients who are intolerant or develop resistance to crizotinib.	Crizotinib	162-172	ALK receptor tyrosine kinase	Homo sapiens	88-91
26294238-8	2015	CONCLUSION: The tyrosine kinase inhibitors crizotinib and ceritinib provide an effective treatment approach for patients with ALK-mutated NSCLC.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	126-129
26389762-2	2015	The field has rapidly progressed through development of the first-generation ALK inhibitor, crizotinib, to an understanding of mechanisms of acquired resistance to crizotinib and is currently witnessing an explosion in the development of next-generation ALK inhibitors such as ceritinib, alectinib, PF-06463922, AP26113, X-396, and TSR-011.	Crizotinib	92-102	ALK receptor tyrosine kinase	Homo sapiens	77-80
25682546-11	2015	CONCLUSION: ALK-positive patients showed a greater RR and longer PFS with pemetrexed-based therapy than patients without ALK rearrangements, suggesting that pemetrexed should be preferentially considered for the treatment of ALK-positive lung adenocarcinoma when use of crizotinib is not feasible.	Crizotinib	270-280	ALK receptor tyrosine kinase	Homo sapiens	12-15
26327925-3	2015	Crizotinib, an ALK inhibitor, is effective in treating advanced ALK-positive NSCLC, and the US Food and Drug Administration approved it for treating ALK-positive NSCLC in 2011.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	15-18
25922291-0	2015	Detection of Crizotinib-Sensitive Lung Adenocarcinomas With MET, ALK, and ROS1 Genomic Alterations via Comprehensive Genomic Profiling.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	65-68
25922291-0	2015	Detection of Crizotinib-Sensitive Lung Adenocarcinomas With MET, ALK, and ROS1 Genomic Alterations via Comprehensive Genomic Profiling.	Crizotinib	13-23	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	74-78
26258416-0	2015	Reversal of microRNA-150 silencing disadvantages crizotinib-resistant NPM-ALK(+) cell growth.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	74-77
26258416-9	2015	Treatment of crizotinib-resistant NPM-ALK(+) KARPAS-299-CR06 cells with decitabine or ectopic miR-150 expression reduced viability and growth.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	38-41
26258416-9	2015	Treatment of crizotinib-resistant NPM-ALK(+) KARPAS-299-CR06 cells with decitabine or ectopic miR-150 expression reduced viability and growth.	Crizotinib	13-23	microRNA 150	Homo sapiens	94-101
26258416-10	2015	Altogether, our results suggest that hypomethylating drugs, alone or in combination with other agents, may benefit ALK(+) patients harboring tumors resistant to crizotinib and other anti-ALK tyrosine kinase inhibitors (TKIs).	Crizotinib	161-171	ALK receptor tyrosine kinase	Homo sapiens	115-118
26142544-1	2015	Crizotinib treatment significantly prolongs progression-free survival, increases response rates, and improves the quality of life in patients with ALK-positive non-small-cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	147-150
26142544-2	2015	Droplet Digital PCR (ddPCR), a recently developed technique with high sensitivity and specificity, was used in this study to evaluate the association between the abundance of ALK rearrangements and crizotinib effectiveness.	Crizotinib	198-208	ALK receptor tyrosine kinase	Homo sapiens	175-178
26327925-3	2015	Crizotinib, an ALK inhibitor, is effective in treating advanced ALK-positive NSCLC, and the US Food and Drug Administration approved it for treating ALK-positive NSCLC in 2011.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	64-67
26327925-3	2015	Crizotinib, an ALK inhibitor, is effective in treating advanced ALK-positive NSCLC, and the US Food and Drug Administration approved it for treating ALK-positive NSCLC in 2011.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	64-67
26345996-2	2015	EXPERIMENTAL DESIGN: Met TKI inhibitor PF-2341066 alone, or in combination with cisplatin, was investigated for its ability to block HGF-induced signaling and biological effects in vitro and in vivo.	Crizotinib	39-49	hepatocyte growth factor	Homo sapiens	133-136
26813592-7	2015	Six patients with ALK IHC-positive result were followed up to analyze the responses of crizotinib therapy.	Crizotinib	87-97	ALK receptor tyrosine kinase	Homo sapiens	18-21
26813592-16	2015	The six patients with positive ALK protein expression received crizotinib therapy, and 5 paitents got treated effectively.	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	31-34
26258422-4	2015	RESULTS from phase I clinical studies using the ROS1 inhibitor crizotinib indicate response rates of 70 - 80% and a median progression-free survival of about 19 months.	Crizotinib	63-73	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	48-52
26295973-11	2015	Notably, a metastatic MTC case harboring the EML4-ALK fusion showed a dramatic response to an ALK inhibitor, crizotinib.	Crizotinib	109-119	EMAP like 4	Homo sapiens	45-49
26295973-11	2015	Notably, a metastatic MTC case harboring the EML4-ALK fusion showed a dramatic response to an ALK inhibitor, crizotinib.	Crizotinib	109-119	ALK receptor tyrosine kinase	Homo sapiens	50-53
26295973-11	2015	Notably, a metastatic MTC case harboring the EML4-ALK fusion showed a dramatic response to an ALK inhibitor, crizotinib.	Crizotinib	109-119	ALK receptor tyrosine kinase	Homo sapiens	94-97
26271036-2	2015	For example, the anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor crizotinib causes characteristic visual disturbances, whereas such effects are rare when another ALK-tyrosine kinase inhibitor, alectinib, is used.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	17-43
26271036-2	2015	For example, the anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor crizotinib causes characteristic visual disturbances, whereas such effects are rare when another ALK-tyrosine kinase inhibitor, alectinib, is used.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	45-48
26271036-2	2015	For example, the anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor crizotinib causes characteristic visual disturbances, whereas such effects are rare when another ALK-tyrosine kinase inhibitor, alectinib, is used.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	173-176
26271036-7	2015	Finally, the expressions of ALK (a target receptor of both crizotinib and alectinib) and of MET and ROS1 (additional target receptors of crizotinib) were observed at the mRNA level in the retina.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	28-31
26271036-7	2015	Finally, the expressions of ALK (a target receptor of both crizotinib and alectinib) and of MET and ROS1 (additional target receptors of crizotinib) were observed at the mRNA level in the retina.	Crizotinib	137-147	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	100-104
26253541-1	2015	INTRODUCTION: The rearrangement of the anaplastic lymphoma kinase (ALK) gene accounts for approximately 1%-6% of lung adenocarcinoma cases and defines a molecular subgroup of tumors characterized by clinical sensitivity to ALK inhibitors such as crizotinib.	Crizotinib	246-256	ALK receptor tyrosine kinase	Homo sapiens	39-65
26253541-1	2015	INTRODUCTION: The rearrangement of the anaplastic lymphoma kinase (ALK) gene accounts for approximately 1%-6% of lung adenocarcinoma cases and defines a molecular subgroup of tumors characterized by clinical sensitivity to ALK inhibitors such as crizotinib.	Crizotinib	246-256	ALK receptor tyrosine kinase	Homo sapiens	67-70
26253541-1	2015	INTRODUCTION: The rearrangement of the anaplastic lymphoma kinase (ALK) gene accounts for approximately 1%-6% of lung adenocarcinoma cases and defines a molecular subgroup of tumors characterized by clinical sensitivity to ALK inhibitors such as crizotinib.	Crizotinib	246-256	ALK receptor tyrosine kinase	Homo sapiens	223-226
26253541-2	2015	This study aimed to identify the relationship between ALK rearrangement and the clinicopathologic characteristics of non-small cell lung cancer (NSCLC) and to analyze the therapeutic responses of crizotinib and conventional chemotherapy to ALK rearrangement in NSCLC patients.	Crizotinib	196-206	ALK receptor tyrosine kinase	Homo sapiens	240-243
26029864-0	2015	Treatment, overall survival, and costs in patients with ALK-positive non-small-cell lung cancer after crizotinib monotherapy.	Crizotinib	102-112	ALK receptor tyrosine kinase	Homo sapiens	56-59
26029864-1	2015	BACKGROUND: Limited post-crizotinib treatment options for ALK-positive non-small cell lung cancer (NSCLC) might lead to poor survival and high economic burden.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	58-61
26029864-10	2015	RESULTS: A total of 119 ALK-positive NSCLC patients discontinued crizotinib monotherapy.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	24-27
26029864-13	2015	From claims data, 305 ALK-positive NSCLC patients discontinued crizotinib monotherapy.	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	22-25
25775951-7	2015	Higher HGF secretion activated Akt signaling pathway, which was reversed by HGF receptor inhibitor (crizotinib).	Crizotinib	100-110	hepatocyte growth factor	Homo sapiens	7-10
25775951-7	2015	Higher HGF secretion activated Akt signaling pathway, which was reversed by HGF receptor inhibitor (crizotinib).	Crizotinib	100-110	AKT serine/threonine kinase 1	Homo sapiens	31-34
25775951-7	2015	Higher HGF secretion activated Akt signaling pathway, which was reversed by HGF receptor inhibitor (crizotinib).	Crizotinib	100-110	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	76-88
26310368-1	2015	BACKGROUND: This investigation sought to elucidate the relationship between hepatocyte growth factor (HGF)-induced metastatic behavior and the tyrosine kinase inhibitors (TKIs) crizotinib and dasatinib in canine osteosarcoma (OS).	Crizotinib	177-187	hepatocyte growth factor	Canis lupus familiaris	76-100
26310368-1	2015	BACKGROUND: This investigation sought to elucidate the relationship between hepatocyte growth factor (HGF)-induced metastatic behavior and the tyrosine kinase inhibitors (TKIs) crizotinib and dasatinib in canine osteosarcoma (OS).	Crizotinib	177-187	hepatocyte growth factor	Canis lupus familiaris	102-105
26310368-7	2015	Dasatinib suppressed OS cell viability and HGF-induced invasion and migration, whereas crizotinib reduced migration and MMP-9 production but did not inhibit invasion or viability.	Crizotinib	87-97	matrix metallopeptidase 9	Canis lupus familiaris	120-125
26703339-0	2015	[Relationship between expression of anaplastic lymphoma kinase in pleural effusion and clinicopathological features of patients with lung adenocarcinoma and the response to crizotinib].	Crizotinib	173-183	ALK receptor tyrosine kinase	Homo sapiens	36-62
26703339-1	2015	OBJECTIVE: To explore the expression of anaplastic lymphoma kinase (ALK) protein in pleural effusion cells from patients with lung adenocarcinoma and to investigate the relationship between ALK status and the clinicopathological features, and the response to crizotinib.	Crizotinib	259-269	ALK receptor tyrosine kinase	Homo sapiens	40-66
26703339-1	2015	OBJECTIVE: To explore the expression of anaplastic lymphoma kinase (ALK) protein in pleural effusion cells from patients with lung adenocarcinoma and to investigate the relationship between ALK status and the clinicopathological features, and the response to crizotinib.	Crizotinib	259-269	ALK receptor tyrosine kinase	Homo sapiens	68-71
26703339-10	2015	Among the 13 ALK-positive patients, 4 received crizotinib therapy, and all showed partial response.	Crizotinib	47-57	ALK receptor tyrosine kinase	Homo sapiens	13-16
26703339-12	2015	Screening ALK fusion protein expression in patients with lung adenocarcinoma by paraffin-embedded sediments of pleural effusion was useful in guide of crizotinib therapy.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	10-13
25953441-2	2015	New chemotherapy agents, such as crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK) and ROS1, usually used in pretreated advanced ALK-positive non-small-cell lung carcinoma, are more often used, and a description of the onset of side effects with suggestions for their management could be of interest for physicians.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	61-87
25953441-2	2015	New chemotherapy agents, such as crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK) and ROS1, usually used in pretreated advanced ALK-positive non-small-cell lung carcinoma, are more often used, and a description of the onset of side effects with suggestions for their management could be of interest for physicians.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	89-92
25953441-2	2015	New chemotherapy agents, such as crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK) and ROS1, usually used in pretreated advanced ALK-positive non-small-cell lung carcinoma, are more often used, and a description of the onset of side effects with suggestions for their management could be of interest for physicians.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	140-143
31149429-1	2016	We report a case of 50-year-old Japanese female with anaplastic lymphoma kinase (ALK)-positive, crizotinib-resistant lung adenocarcinoma, whose leptomeningeal carcinomatosis and spinal cord metastases were dramatically improved by the second-generation ALK inhibitor alectinib.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	53-79
31149429-1	2016	We report a case of 50-year-old Japanese female with anaplastic lymphoma kinase (ALK)-positive, crizotinib-resistant lung adenocarcinoma, whose leptomeningeal carcinomatosis and spinal cord metastases were dramatically improved by the second-generation ALK inhibitor alectinib.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	81-84
31149429-1	2016	We report a case of 50-year-old Japanese female with anaplastic lymphoma kinase (ALK)-positive, crizotinib-resistant lung adenocarcinoma, whose leptomeningeal carcinomatosis and spinal cord metastases were dramatically improved by the second-generation ALK inhibitor alectinib.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	253-256
26168728-4	2015	Enzyme assay shows that KRCA-0080 is more potent against various ALK mutants, including L1196M, G1202R, T1151_L1152insT, and C1156Y, which are seen in crizotinib-resistant patients, than KRCA-0008 is.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	65-68
26312204-2	2015	Crizotinib, an ALK tyrosine kinase inhibitor, is currently approved to treat lung cancer patients exhibiting ALK gene rearrangements.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	15-18
26312204-2	2015	Crizotinib, an ALK tyrosine kinase inhibitor, is currently approved to treat lung cancer patients exhibiting ALK gene rearrangements.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	109-112
26018086-2	2015	The ALK kinase inhibitors crizotinib and ceritinib are approved for relapsed ALK(+) NSCLC, but acquired resistance to these drugs limits median progression-free survival on average to ~10 months.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	4-7
26018086-2	2015	The ALK kinase inhibitors crizotinib and ceritinib are approved for relapsed ALK(+) NSCLC, but acquired resistance to these drugs limits median progression-free survival on average to ~10 months.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	77-80
25846554-10	2015	Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02).	Crizotinib	98-108	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	15-19
25801645-0	2015	The efficacy of crizotinib in patients with ALK-positive nonsmall cell lung cancer.	Crizotinib	16-26	ALK receptor tyrosine kinase	Homo sapiens	44-47
25908037-5	2015	Crizotinib is an oral tyrosine kinase inhibitor that binds the ALK tyrosine kinase domain, blocking its function.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	63-66
25724526-0	2015	Progression-Free and Overall Survival in ALK-Positive NSCLC Patients Treated with Sequential Crizotinib and Ceritinib.	Crizotinib	93-103	ALK receptor tyrosine kinase	Homo sapiens	41-44
25724526-1	2015	PURPOSE: Anaplastic lymphoma kinase (ALK) rearrangements are important therapeutic targets in non-small cell lung cancer (NSCLC) that confer sensitivity to the ALK inhibitors crizotinib and ceritinib.	Crizotinib	175-185	ALK receptor tyrosine kinase	Homo sapiens	9-35
25724526-1	2015	PURPOSE: Anaplastic lymphoma kinase (ALK) rearrangements are important therapeutic targets in non-small cell lung cancer (NSCLC) that confer sensitivity to the ALK inhibitors crizotinib and ceritinib.	Crizotinib	175-185	ALK receptor tyrosine kinase	Homo sapiens	37-40
25724526-1	2015	PURPOSE: Anaplastic lymphoma kinase (ALK) rearrangements are important therapeutic targets in non-small cell lung cancer (NSCLC) that confer sensitivity to the ALK inhibitors crizotinib and ceritinib.	Crizotinib	175-185	ALK receptor tyrosine kinase	Homo sapiens	160-163
25724526-3	2015	EXPERIMENTAL DESIGN: We identified 73 ALK-positive NSCLC patients treated with crizotinib followed by ceritinib at four institutions.	Crizotinib	79-89	ALK receptor tyrosine kinase	Homo sapiens	38-41
25724526-5	2015	RESULTS: Among 73 ALK-positive patients, the median PFS (mPFS) on crizotinib was 8.2 months [95% confidence interval (CI), 7.4-10.6].	Crizotinib	66-76	ALK receptor tyrosine kinase	Homo sapiens	18-21
26062823-9	2015	The patient was enrolled in a clinical trial and treated with an anaplastic lymphoma kinase (ALK) inhibitor (crizotinib/Xalkori ) and a multikinase VEGF inhibitor (pazopanib/Votrient ).	Crizotinib	109-119	ALK receptor tyrosine kinase	Homo sapiens	93-96
25624436-0	2015	Clinical Experience With Crizotinib in Patients With Advanced ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastases.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	62-65
25624436-1	2015	PURPOSE: Crizotinib is an oral kinase inhibitor approved for the treatment of ALK-rearranged non-small-cell lung cancer (NSCLC).	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	78-81
25624436-11	2015	CONCLUSION: Crizotinib was associated with systemic and intracranial disease control in patients with ALK-rearranged NSCLC who were ALK inhibitor naive and had brain metastases.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	102-105
25624436-11	2015	CONCLUSION: Crizotinib was associated with systemic and intracranial disease control in patients with ALK-rearranged NSCLC who were ALK inhibitor naive and had brain metastases.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	132-135
26082648-0	2015	Alectinib for choroidal metastasis in a patient with crizotinib-resistant ALK rearranged positive non-small cell lung cancer.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	74-77
26082648-5	2015	A 30-year-old female patient previously treated with crizotinib harboring ALK rearranged non-small cell lung cancer complained of visual disturbance, fever, and bone pains undergoing anti-PD-1 antibody treatment.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	74-77
25756473-1	2015	An apparent causal association between crizotinib treatment and renal cyst development emerged during clinical trials in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	121-147
25756473-1	2015	An apparent causal association between crizotinib treatment and renal cyst development emerged during clinical trials in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	149-152
25756473-9	2015	Crizotinib treatment appears to be associated with an increased risk of development and progression of renal cysts in patients with ALK-positive NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	132-135
26032424-4	2015	Strikingly, both mutations conferred sensitivity to ALK kinase inhibitors, including the FDA-approved drug crizotinib.	Crizotinib	107-117	ALK receptor tyrosine kinase	Homo sapiens	52-55
25652176-1	2015	Crizotinib was the first clinically available anaplastic lymphoma kinase (ALK) inhibitor, showing remarkable activity against ALK-rearranged non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	46-72
25652176-1	2015	Crizotinib was the first clinically available anaplastic lymphoma kinase (ALK) inhibitor, showing remarkable activity against ALK-rearranged non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	74-77
25652176-1	2015	Crizotinib was the first clinically available anaplastic lymphoma kinase (ALK) inhibitor, showing remarkable activity against ALK-rearranged non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	126-129
25652176-3	2015	Alectinib is a highly selective, next-generation ALK inhibitor with potent inhibitory activity also against ALK mutations conferring resistance to crizotinib, including the gatekeeper L1196M substitution.	Crizotinib	147-157	ALK receptor tyrosine kinase	Homo sapiens	108-111
26001146-0	2015	Diffuse Hemorrhagic Brain Metastases in an ALK Fusion Positive Patient on Crizotinib.	Crizotinib	74-84	ALK receptor tyrosine kinase	Homo sapiens	43-46
26001149-1	2015	PATIENTS: With advanced non-small-cell lung cancer (NSCLC) harboring, the anaplastic lymphoma kinase (ALK) gene rearrangement often responds impressively to ALK inhibitors, such as crizotinib.	Crizotinib	181-191	ALK receptor tyrosine kinase	Homo sapiens	74-100
26001149-1	2015	PATIENTS: With advanced non-small-cell lung cancer (NSCLC) harboring, the anaplastic lymphoma kinase (ALK) gene rearrangement often responds impressively to ALK inhibitors, such as crizotinib.	Crizotinib	181-191	ALK receptor tyrosine kinase	Homo sapiens	102-105
26001149-1	2015	PATIENTS: With advanced non-small-cell lung cancer (NSCLC) harboring, the anaplastic lymphoma kinase (ALK) gene rearrangement often responds impressively to ALK inhibitors, such as crizotinib.	Crizotinib	181-191	ALK receptor tyrosine kinase	Homo sapiens	157-160
25837798-1	2015	Crizotinib was the first clinically available inhibitor of the tyrosine kinase ALK, and next-generation ALK inhibitors, such as alectinib, are now under development.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	79-82
25851827-3	2015	While crizotinib, a multi-targeted ALK/ROS1/MET tyrosine kinase inhibitor (TKI), has demonstrated significant clinical activity in ROS1-rearranged NSCLC, no companion diagnostic assay has been approved for the detection of ROS1-rearrange NSCLC by the US FDA.	Crizotinib	6-16	ALK receptor tyrosine kinase	Homo sapiens	35-38
25851827-3	2015	While crizotinib, a multi-targeted ALK/ROS1/MET tyrosine kinase inhibitor (TKI), has demonstrated significant clinical activity in ROS1-rearranged NSCLC, no companion diagnostic assay has been approved for the detection of ROS1-rearrange NSCLC by the US FDA.	Crizotinib	6-16	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	39-43
25851827-3	2015	While crizotinib, a multi-targeted ALK/ROS1/MET tyrosine kinase inhibitor (TKI), has demonstrated significant clinical activity in ROS1-rearranged NSCLC, no companion diagnostic assay has been approved for the detection of ROS1-rearrange NSCLC by the US FDA.	Crizotinib	6-16	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	131-135
25851827-3	2015	While crizotinib, a multi-targeted ALK/ROS1/MET tyrosine kinase inhibitor (TKI), has demonstrated significant clinical activity in ROS1-rearranged NSCLC, no companion diagnostic assay has been approved for the detection of ROS1-rearrange NSCLC by the US FDA.	Crizotinib	6-16	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	131-135
25966792-0	2015	Efficacy and tolerability of crizotinib in the treatment of ALK-positive, advanced non-small cell lung cancer in Chinese patients.	Crizotinib	29-39	ALK receptor tyrosine kinase	Homo sapiens	60-63
25966792-1	2015	Crizotinib has been reported to be particularly effective and to have acceptable toxicity in advanced anaplastic lymphoma kinase (ALK)-positive, non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	102-128
25966792-1	2015	Crizotinib has been reported to be particularly effective and to have acceptable toxicity in advanced anaplastic lymphoma kinase (ALK)-positive, non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	130-133
25966792-2	2015	In this study, we analyzed the efficacy and tolerability of crizotinib in the treatment of 72 Chinese patients with ALK-positive, advanced NSCLC.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	116-119
25966792-12	2015	Thus, crizotinib was well tolerated and showed promising efficacy in Chinese patients with ALK-positive, advanced NSCLC.	Crizotinib	6-16	ALK receptor tyrosine kinase	Homo sapiens	91-94
25727400-0	2015	Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	30-33
25727400-0	2015	Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK.	Crizotinib	53-63	nucleophosmin 1	Homo sapiens	88-91
25727400-0	2015	Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	92-95
25727400-0	2015	Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	92-95
25727400-3	2015	The ALK/c-MET/ROS inhibitor crizotinib successfully improved the treatment of ALK-driven diseases.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	4-7
25727400-3	2015	The ALK/c-MET/ROS inhibitor crizotinib successfully improved the treatment of ALK-driven diseases.	Crizotinib	28-38	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	8-13
25727400-3	2015	The ALK/c-MET/ROS inhibitor crizotinib successfully improved the treatment of ALK-driven diseases.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	78-81
25727400-4	2015	However, several cases of resistance appeared in NSCLC patients, and ALK amino acid substitutions were identified as a leading cause of resistance to crizotinib.	Crizotinib	150-160	ALK receptor tyrosine kinase	Homo sapiens	69-72
25727400-5	2015	Second-generation ALK inhibitors have been developed in order to overcome crizotinib resistance.	Crizotinib	74-84	ALK receptor tyrosine kinase	Homo sapiens	18-21
25727400-6	2015	In this work, we profiled in vitro the activity of crizotinib, AP26113, ASP3026, alectinib, and ceritinib against six mutated forms of ALK associated with clinical resistance to crizotinib (C1156Y, L1196M, L1152R, G1202R, G1269A, and S1206Y) and provide a classification of mutants according to their level of sensitivity/resistance to the drugs.	Crizotinib	51-61	ALK receptor tyrosine kinase	Homo sapiens	135-138
25727400-6	2015	In this work, we profiled in vitro the activity of crizotinib, AP26113, ASP3026, alectinib, and ceritinib against six mutated forms of ALK associated with clinical resistance to crizotinib (C1156Y, L1196M, L1152R, G1202R, G1269A, and S1206Y) and provide a classification of mutants according to their level of sensitivity/resistance to the drugs.	Crizotinib	178-188	ALK receptor tyrosine kinase	Homo sapiens	135-138
26076736-3	2015	Crizotinib is a first-in-class ALK tyrosine kinase inhibitor with significant activity in ALK-positive NSCLC that received accelerated US Food and Drug Administration approval for treatment of ALK-positive NSCLC in 2011, just 4 years after identification of ALK rearrangements in this setting.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	31-34
26076736-3	2015	Crizotinib is a first-in-class ALK tyrosine kinase inhibitor with significant activity in ALK-positive NSCLC that received accelerated US Food and Drug Administration approval for treatment of ALK-positive NSCLC in 2011, just 4 years after identification of ALK rearrangements in this setting.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	90-93
26076736-3	2015	Crizotinib is a first-in-class ALK tyrosine kinase inhibitor with significant activity in ALK-positive NSCLC that received accelerated US Food and Drug Administration approval for treatment of ALK-positive NSCLC in 2011, just 4 years after identification of ALK rearrangements in this setting.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	90-93
26076736-3	2015	Crizotinib is a first-in-class ALK tyrosine kinase inhibitor with significant activity in ALK-positive NSCLC that received accelerated US Food and Drug Administration approval for treatment of ALK-positive NSCLC in 2011, just 4 years after identification of ALK rearrangements in this setting.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	90-93
26076736-4	2015	Subsequently, two phase III trials have shown crizotinib to have a tolerable toxicity profile and to be superior to standard chemotherapy for the first- or second-line treatment of advanced ALK-positive lung cancer and numerous countries have approved its use.	Crizotinib	46-56	ALK receptor tyrosine kinase	Homo sapiens	190-193
26076736-7	2015	Several next-generation ALK inhibitors, including ceritinib and alectinib, are in clinical development and show efficacy in both the crizotinib naive and crizotinib refractory settings.	Crizotinib	133-143	ALK receptor tyrosine kinase	Homo sapiens	24-27
26076736-7	2015	Several next-generation ALK inhibitors, including ceritinib and alectinib, are in clinical development and show efficacy in both the crizotinib naive and crizotinib refractory settings.	Crizotinib	154-164	ALK receptor tyrosine kinase	Homo sapiens	24-27
25929953-5	2015	Second-generation ALK inhibitors are currently being evaluated, with early studies giving impressive results, notably in patients resistant to crizotinib or with brain metastases.	Crizotinib	143-153	ALK receptor tyrosine kinase	Homo sapiens	18-21
25929957-1	2015	Anaplastic lymphoma kinase (ALK) gene rearrangements in lung adenocarcinoma result in kinase activity targetable by crizotinib.	Crizotinib	116-126	ALK receptor tyrosine kinase	Homo sapiens	28-31
26134230-0	2015	Cystic Brain Metastases in NSCLC Harboring the EML4-ALK Translocation after Treatment with Crizotinib.	Crizotinib	91-101	EMAP like 4	Homo sapiens	47-51
26134230-0	2015	Cystic Brain Metastases in NSCLC Harboring the EML4-ALK Translocation after Treatment with Crizotinib.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	52-55
26380734-0	2015	Clinical efficacy of crizotinib in Chinese patients with ALK-positive non-small-cell lung cancer with brain metastases.	Crizotinib	21-31	ALK receptor tyrosine kinase	Homo sapiens	57-60
26380734-1	2015	BACKGROUND: Crizotinib has been associated with intracranial disease control in anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients with brain metastases.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	80-106
26380734-1	2015	BACKGROUND: Crizotinib has been associated with intracranial disease control in anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients with brain metastases.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	108-111
26380734-3	2015	However, there are few studies of crizotinib efficacy in ALK-positive Chinese patients.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	57-60
26380734-12	2015	CONCLUSIONS: Chinese ALK-positive NSCLC patients with brain metastases achieved a similar response to crizotinib and significantly shorter PFS compared to those without brain metastases at baseline.	Crizotinib	102-112	ALK receptor tyrosine kinase	Homo sapiens	21-24
26025486-7	2015	The annexin V/PI staining-based apoptosis assay showed a remarkable ~40 % apoptosis (early and late apoptosis cells) comparing to only ~25 % apoptosis by free CZT.	Crizotinib	159-162	annexin A5	Homo sapiens	4-13
26171201-1	2015	Therapy with crizotinib achieves prolonged progression-free and overall survival in non-small-cell lung cancer (NSCLC) patients with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK).	Crizotinib	13-23	EMAP like 4	Homo sapiens	133-181
26171201-1	2015	Therapy with crizotinib achieves prolonged progression-free and overall survival in non-small-cell lung cancer (NSCLC) patients with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK).	Crizotinib	13-23	EMAP like 4	Homo sapiens	183-187
26171201-1	2015	Therapy with crizotinib achieves prolonged progression-free and overall survival in non-small-cell lung cancer (NSCLC) patients with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK).	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	217-220
26171201-2	2015	It was demonstrated that ALK-positive NSCLCs exhibit a high response rate to the ALK inhibitor, crizotinib.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	25-28
26171201-2	2015	It was demonstrated that ALK-positive NSCLCs exhibit a high response rate to the ALK inhibitor, crizotinib.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	81-84
26171201-4	2015	This is the case report of a NSCLC patient with EML4-ALK rearrangement, who, following crizotinib discontinuation for one year due to adverse events, exhibited a marked response to alectinib.	Crizotinib	87-97	EMAP like 4	Homo sapiens	48-52
26171201-4	2015	This is the case report of a NSCLC patient with EML4-ALK rearrangement, who, following crizotinib discontinuation for one year due to adverse events, exhibited a marked response to alectinib.	Crizotinib	87-97	ALK receptor tyrosine kinase	Homo sapiens	53-56
25801645-2	2015	The discovery of oncogenic ALK rearrangements in NSCLC and the subsequent success in their therapeutic targeting with crizotinib reinforces the benefits of a precision approach to systemic anticancer therapy.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	27-30
25801645-4	2015	In this review we describe the identification of ALK rearranged NSCLC, clinical characteristics of such patients, and clinical outcomes when treated with crizotinib.	Crizotinib	154-164	ALK receptor tyrosine kinase	Homo sapiens	49-52
25588859-0	2015	Lung adenocarcinoma with concurrent KRAS mutation and ALK rearrangement responding to crizotinib: case report.	Crizotinib	86-96	ALK receptor tyrosine kinase	Homo sapiens	54-57
25588859-5	2015	This patient had an excellent response to crizotinib, suggesting that the ALK translocation was the oncogenic driver.	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	74-77
25688157-1	2015	PURPOSE: Although ROS1-rearranged non-small cell lung cancer (NSCLC) is sensitive to crizotinib, development of resistance is inevitable.	Crizotinib	85-95	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	18-22
25688157-2	2015	Here, we identified molecular alterations in crizotinib-resistant tumors from two NSCLC patients with the CD74-ROS1 rearrangement, and in HCC78 cells harboring SLC34A2-ROS1 that showed resistance to crizotinib (HCC78CR cells).	Crizotinib	45-55	CD74 molecule	Homo sapiens	106-110
25688157-2	2015	Here, we identified molecular alterations in crizotinib-resistant tumors from two NSCLC patients with the CD74-ROS1 rearrangement, and in HCC78 cells harboring SLC34A2-ROS1 that showed resistance to crizotinib (HCC78CR cells).	Crizotinib	45-55	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	111-115
25688157-2	2015	Here, we identified molecular alterations in crizotinib-resistant tumors from two NSCLC patients with the CD74-ROS1 rearrangement, and in HCC78 cells harboring SLC34A2-ROS1 that showed resistance to crizotinib (HCC78CR cells).	Crizotinib	199-209	solute carrier family 34 member 2	Homo sapiens	160-167
25688157-7	2015	RESULTS: The ROS1 G2032R mutation was identified in crizotinib-resistant tumors from one patient.	Crizotinib	52-62	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	13-17
25688157-9	2015	ROS1 G2032R and L2155S mutations conferred resistance to crizotinib in Ba/F3 cells.	Crizotinib	57-67	Ros1 proto-oncogene	Mus musculus	0-4
25688157-12	2015	Cells with the ROS1 mutation and upregulated EGFR were sensitive to foretinib, an inhibitor of c-MET, VEGFR2, and ROS1 and irreversible EGFR tyrosine kinase inhibitors plus crizotinib, respectively.	Crizotinib	173-183	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	15-19
25688157-12	2015	Cells with the ROS1 mutation and upregulated EGFR were sensitive to foretinib, an inhibitor of c-MET, VEGFR2, and ROS1 and irreversible EGFR tyrosine kinase inhibitors plus crizotinib, respectively.	Crizotinib	173-183	epidermal growth factor receptor	Homo sapiens	45-49
25688157-13	2015	CONCLUSIONS: Molecular changes associated with acquired crizotinib resistance in ROS1-rearranged NSCLC are heterogeneous, including ROS1 tyrosine kinase mutations, EGFR activation, and epithelial-to-mesenchymal transition.	Crizotinib	56-66	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	81-85
25688157-13	2015	CONCLUSIONS: Molecular changes associated with acquired crizotinib resistance in ROS1-rearranged NSCLC are heterogeneous, including ROS1 tyrosine kinase mutations, EGFR activation, and epithelial-to-mesenchymal transition.	Crizotinib	56-66	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	132-136
25688157-13	2015	CONCLUSIONS: Molecular changes associated with acquired crizotinib resistance in ROS1-rearranged NSCLC are heterogeneous, including ROS1 tyrosine kinase mutations, EGFR activation, and epithelial-to-mesenchymal transition.	Crizotinib	56-66	epidermal growth factor receptor	Homo sapiens	164-168
25979929-4	2015	Several ALK tyrosine kinase inhibitors (TKI), including crizotinib, ceritinib, and alectinib, have been developed, and some of them have already been approved for clinical use.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	8-11
26221234-0	2015	Promising response of anaplastic lymphoma kinase-positive large B-cell lymphoma to crizotinib salvage treatment: case report and review of literature.	Crizotinib	83-93	ALK receptor tyrosine kinase	Homo sapiens	22-48
26221234-3	2015	In view of the expression of ALK in this disease, it is plausible that the ALK inhibitor crizotinib may be an effective treatment.	Crizotinib	89-99	ALK receptor tyrosine kinase	Homo sapiens	29-32
26221234-3	2015	In view of the expression of ALK in this disease, it is plausible that the ALK inhibitor crizotinib may be an effective treatment.	Crizotinib	89-99	ALK receptor tyrosine kinase	Homo sapiens	75-78
26221234-8	2015	We administered two courses of an alternative salvage chemotherapy regimen containing GEMOX and dexamethasone with the addition of the ALK inhibitor crizotinib.	Crizotinib	149-159	ALK receptor tyrosine kinase	Homo sapiens	135-138
28210149-4	2015	Subsequent development of the first-generation tyrosine kinase inhibitor crizotinib demonstrated substantial initial ALK+-tumor regression, yet ultimately displayed resistance in treated patients.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	117-120
25955180-4	2015	These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed.	Crizotinib	166-176	anaplastic lymphoma kinase	Mus musculus	40-43
25955180-4	2015	These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed.	Crizotinib	166-176	anaplastic lymphoma kinase	Mus musculus	136-139
25955180-4	2015	These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed.	Crizotinib	166-176	anaplastic lymphoma kinase	Mus musculus	136-139
25950466-11	2015	Finally, we observed that a treatment combining P36 with the ALK-specific inhibitor crizotinib resulted in additive cytotoxicity.	Crizotinib	84-94	ALK receptor tyrosine kinase	Homo sapiens	61-64
25999733-2	2015	Crizotinib was developed and introduced into clinical practice rapidly and successfully after the discovery of ALK rearrangement in non-small-cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	111-114
25999733-4	2015	Crizotinib showed potent antitumor activity and manageable toxicity in mesenchymal-epithelial transition factor (c-Met)/ROS1-positive non-small-cell lung cancer patients, but prospective clinical trials are still needed to confirm its efficacy and safety.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	113-118
25999733-4	2015	Crizotinib showed potent antitumor activity and manageable toxicity in mesenchymal-epithelial transition factor (c-Met)/ROS1-positive non-small-cell lung cancer patients, but prospective clinical trials are still needed to confirm its efficacy and safety.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	120-124
25999733-5	2015	Crizotinib appears to be effective against tumors originating from various organs that harbor ALK abnormalities.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	94-97
25999733-7	2015	The major challenge of the widespread use of crizotinib in clinical practice is establishing convenient diagnostic techniques for the detection of ALK/c-Met/ROS1.	Crizotinib	45-55	ALK receptor tyrosine kinase	Homo sapiens	147-150
25999733-7	2015	The major challenge of the widespread use of crizotinib in clinical practice is establishing convenient diagnostic techniques for the detection of ALK/c-Met/ROS1.	Crizotinib	45-55	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	151-156
25999733-7	2015	The major challenge of the widespread use of crizotinib in clinical practice is establishing convenient diagnostic techniques for the detection of ALK/c-Met/ROS1.	Crizotinib	45-55	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	157-161
25732197-1	2015	INTRODUCTION: For a subpopulation of NSCLC patients genetic rearrangement of the anaplastic lymphoma kinase (ALK) was found as driver mutation, which can be targeted by the selective inhibitor crizotinib.	Crizotinib	193-203	ALK receptor tyrosine kinase	Homo sapiens	81-107
25732197-1	2015	INTRODUCTION: For a subpopulation of NSCLC patients genetic rearrangement of the anaplastic lymphoma kinase (ALK) was found as driver mutation, which can be targeted by the selective inhibitor crizotinib.	Crizotinib	193-203	ALK receptor tyrosine kinase	Homo sapiens	109-112
25732197-8	2015	Despite the one-fits-all approach in administration of crizotinib at a fixed dose the pharmacokinetic parameters indicate a stable steady state upon continuous administration, which achieves sufficient inhibition of the ALK drug target.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	220-223
25270523-7	2015	CONCLUSION: To the best of our knowledge, this is the first case report demonstrating the clinical benefit of crizotinib in sarcomatoid carcinoma of the head and neck with ALK translocation.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	172-175
25898958-4	2015	METHODS: Twenty ALK IHC-positive patients including six patients treated with crizotinib therapy were evaluated for the presence of ALK FISH.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	132-135
25902175-0	2015	Response to Crizotinib/Erlotinib Combination in a Patient with a Primary EGFR-Mutant Adenocarcinoma and a Primary c-met-Amplified Adenocarcinoma of the Lung.	Crizotinib	12-22	epidermal growth factor receptor	Homo sapiens	73-77
25902175-0	2015	Response to Crizotinib/Erlotinib Combination in a Patient with a Primary EGFR-Mutant Adenocarcinoma and a Primary c-met-Amplified Adenocarcinoma of the Lung.	Crizotinib	12-22	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	114-119
25902175-6	2015	Off-label use of crizotinib, a potent inhibitor of c-met, was prescribed.	Crizotinib	17-27	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	51-56
25736571-1	2015	OBJECTIVES: Acquired resistance mutations to anaplastic lymphoma kinase (ALK) inhibitors such as crizotinib and alectinib have been documented in non-small cell lung cancer (NSCLC) patients harboring ALK rearrangement (ALK+).	Crizotinib	97-107	ALK receptor tyrosine kinase	Homo sapiens	45-71
25736571-1	2015	OBJECTIVES: Acquired resistance mutations to anaplastic lymphoma kinase (ALK) inhibitors such as crizotinib and alectinib have been documented in non-small cell lung cancer (NSCLC) patients harboring ALK rearrangement (ALK+).	Crizotinib	97-107	ALK receptor tyrosine kinase	Homo sapiens	73-76
25736571-1	2015	OBJECTIVES: Acquired resistance mutations to anaplastic lymphoma kinase (ALK) inhibitors such as crizotinib and alectinib have been documented in non-small cell lung cancer (NSCLC) patients harboring ALK rearrangement (ALK+).	Crizotinib	97-107	ALK receptor tyrosine kinase	Homo sapiens	200-203
25736571-1	2015	OBJECTIVES: Acquired resistance mutations to anaplastic lymphoma kinase (ALK) inhibitors such as crizotinib and alectinib have been documented in non-small cell lung cancer (NSCLC) patients harboring ALK rearrangement (ALK+).	Crizotinib	97-107	ALK receptor tyrosine kinase	Homo sapiens	200-203
25736571-8	2015	Substitutions of isoleucine at amino acid 1171 in the ALK kinase domain may distinguish which second generation ALK inhibitor will be effective after crizotinib failure.	Crizotinib	150-160	ALK receptor tyrosine kinase	Homo sapiens	54-57
25736571-8	2015	Substitutions of isoleucine at amino acid 1171 in the ALK kinase domain may distinguish which second generation ALK inhibitor will be effective after crizotinib failure.	Crizotinib	150-160	ALK receptor tyrosine kinase	Homo sapiens	112-115
26018277-0	2015	[Therapeutic effects of crizotinib in EML4-ALK-positive patients with non-small-cell lung cancer].	Crizotinib	24-34	EMAP like 4	Homo sapiens	38-42
25941796-1	2015	The discovery of an echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene led to improved clinical outcomes in patients with lung cancer after the development of the first ALK-targeting agent, crizotinib.	Crizotinib	240-250	EMAP like 4	Homo sapiens	20-68
25941796-1	2015	The discovery of an echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene led to improved clinical outcomes in patients with lung cancer after the development of the first ALK-targeting agent, crizotinib.	Crizotinib	240-250	EMAP like 4	Homo sapiens	70-74
25941796-1	2015	The discovery of an echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene led to improved clinical outcomes in patients with lung cancer after the development of the first ALK-targeting agent, crizotinib.	Crizotinib	240-250	ALK receptor tyrosine kinase	Homo sapiens	104-107
25941796-1	2015	The discovery of an echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene led to improved clinical outcomes in patients with lung cancer after the development of the first ALK-targeting agent, crizotinib.	Crizotinib	240-250	ALK receptor tyrosine kinase	Homo sapiens	219-222
25941796-2	2015	Some second-generation ALK tyrosine kinase inhibitors (TKIs), which might be more potent than crizotinib or effective on crizotinib-resistant patients, have been developed.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	23-26
25941796-2	2015	Some second-generation ALK tyrosine kinase inhibitors (TKIs), which might be more potent than crizotinib or effective on crizotinib-resistant patients, have been developed.	Crizotinib	121-131	ALK receptor tyrosine kinase	Homo sapiens	23-26
25868855-1	2015	BACKGROUND: While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients.	Crizotinib	40-50	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	88-92
25868855-12	2015	CONCLUSION: ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far.	Crizotinib	78-88	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	12-16
25744866-0	2015	Neoadjuvant crizotinib in advanced inflammatory myofibroblastic tumour with ALK gene rearrangement.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	76-79
25744866-6	2015	CASE REPORT: We report a rapid early response to crizotinib as neoadjuvant therapy, enabling surgical excision of a large ALK-translocated IMT, which resulted in complete disease clearance.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	122-125
25899913-0	2015	Effective Crizotinib schedule for an elderly patient with ALK rearranged non-small-cell lung cancer: a case report.	Crizotinib	10-20	ALK receptor tyrosine kinase	Homo sapiens	58-61
25899913-1	2015	BACKGROUND: Non-small-cell lung cancers (NSCLCs) harboring translocations in anaplastic lymphoma kinase (ALK) are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib.	Crizotinib	180-190	ALK receptor tyrosine kinase	Homo sapiens	77-103
25899913-1	2015	BACKGROUND: Non-small-cell lung cancers (NSCLCs) harboring translocations in anaplastic lymphoma kinase (ALK) are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib.	Crizotinib	180-190	ALK receptor tyrosine kinase	Homo sapiens	105-108
25899913-1	2015	BACKGROUND: Non-small-cell lung cancers (NSCLCs) harboring translocations in anaplastic lymphoma kinase (ALK) are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib.	Crizotinib	180-190	ALK receptor tyrosine kinase	Homo sapiens	149-152
25899913-9	2015	CONCLUSION: This is the first case report that skip schedule was more effective than dose reduction daily in crizotinib administration for ALK rearranged NSCLC patient with severe adverse events.	Crizotinib	109-119	ALK receptor tyrosine kinase	Homo sapiens	139-142
25945060-5	2015	Unfortunately, most of the patients treated with crizotinib, the first-generation ALK inhibitor, progressed within 9 months.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	82-85
25945060-6	2015	Ceritinib is a second-generation ALK inhibitor that has demonstrated activity in crizotinib-resistant patients, becoming a promising treatment option in this population.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	33-36
25945060-7	2015	Furthermore, additional novel ALK inhibitors and agents targeting alternative pathways have been recruited to rechallenge this evasive disease post-crizotinib resistance.	Crizotinib	148-158	ALK receptor tyrosine kinase	Homo sapiens	30-33
25874976-1	2015	ALK inhibitor crizotinib has shown potent antitumor activity in children with refractory Anaplastic Large Cell Lymphoma (ALCL) and the opportunity to include ALK inhibitors in first-line therapies is oncoming.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	0-3
25874976-8	2015	Consistently, when co-expressed, INDELs increased crizotinib inhibitory activity on NPM-ALK signal processing, as demonstrated by the significant reduction of STAT3 phosphorylation.	Crizotinib	50-60	nucleophosmin 1	Homo sapiens	84-87
25874976-8	2015	Consistently, when co-expressed, INDELs increased crizotinib inhibitory activity on NPM-ALK signal processing, as demonstrated by the significant reduction of STAT3 phosphorylation.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	88-91
25874976-11	2015	These mutations occur randomly within the ALK kinase domain and affect protein activity, while preserving responsiveness to crizotinib.	Crizotinib	124-134	ALK receptor tyrosine kinase	Homo sapiens	42-45
25882375-7	2015	One MET-amplified GC patient responded for 5 months to crizotinib, a multitargeted ALK/ROS1/MET inhibitor.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	83-86
25882375-7	2015	One MET-amplified GC patient responded for 5 months to crizotinib, a multitargeted ALK/ROS1/MET inhibitor.	Crizotinib	55-65	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	87-91
26137041-3	2015	Crizotinib, an anaplastic lymphoma kinase inhibitor, has been approved for the treatment of EML4-ALK NSCLC by previous studies, but its effect on SRCA, an extremely rare subtype of lung adenocarcinoma, has yet to be elucidated.	Crizotinib	0-10	EMAP like 4	Homo sapiens	92-96
26137041-3	2015	Crizotinib, an anaplastic lymphoma kinase inhibitor, has been approved for the treatment of EML4-ALK NSCLC by previous studies, but its effect on SRCA, an extremely rare subtype of lung adenocarcinoma, has yet to be elucidated.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	97-100
25819217-1	2015	The identification of the EML4-ALK rearrangement in 5% of NSCLC enhanced the development of 1st generation ALK inhibitors such as crizotinib.	Crizotinib	130-140	EMAP like 4	Homo sapiens	26-30
25819217-1	2015	The identification of the EML4-ALK rearrangement in 5% of NSCLC enhanced the development of 1st generation ALK inhibitors such as crizotinib.	Crizotinib	130-140	ALK receptor tyrosine kinase	Homo sapiens	31-34
25819217-1	2015	The identification of the EML4-ALK rearrangement in 5% of NSCLC enhanced the development of 1st generation ALK inhibitors such as crizotinib.	Crizotinib	130-140	ALK receptor tyrosine kinase	Homo sapiens	107-110
25994067-1	2015	Crizotinib is an oral small-molecule anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor for the treatment of ALK-positive non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	37-63
25994067-1	2015	Crizotinib is an oral small-molecule anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor for the treatment of ALK-positive non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	65-68
25994067-1	2015	Crizotinib is an oral small-molecule anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor for the treatment of ALK-positive non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	117-120
25994067-2	2015	A 63-year old woman with postoperative relapsed ALK-positive NSCLC was treated with crizotinib.	Crizotinib	84-94	ALK receptor tyrosine kinase	Homo sapiens	48-51
25433426-1	2015	Crizotinib is the first clinically available tyrosine kinase inhibitor that targets anaplastic lymphoma kinase (ALK) and is associated with the development of complex renal cysts.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	84-110
25433426-1	2015	Crizotinib is the first clinically available tyrosine kinase inhibitor that targets anaplastic lymphoma kinase (ALK) and is associated with the development of complex renal cysts.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	112-115
25789835-1	2015	INTRODUCTION: Successful treatment of lung cancer patients with crizotinib depends on the accurate diagnosis of anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	112-156
25789835-1	2015	INTRODUCTION: Successful treatment of lung cancer patients with crizotinib depends on the accurate diagnosis of anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	158-161
25678258-0	2015	Successful treatment of crizotinib-induced dysgeusia by switching to alectinib in ALK-positive non-small cell lung cancer.	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	82-85
25678258-1	2015	We describe a case of dysgeusia that developed gradually over one week after initiation of crizotinib administration for treatment of ALK-positive non-small cell lung cancer, necessitating discontinuation of the agent.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	134-137
25234288-1	2015	The success of crizotinib in ALK-positive patients has elicited efforts to find new oncogenic fusions in lung cancer.	Crizotinib	15-25	ALK receptor tyrosine kinase	Homo sapiens	29-32
25421750-3	2015	Crizotinib was the first clinically relevant ALK inhibitor, now approved for the treatment of late-stage and metastatic cases of lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	45-48
25421750-4	2015	However, patients frequently develop drug resistance to Crizotinib, mainly due to the appearance of point mutations located in the ALK kinase domain.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	131-134
25788996-8	2015	However, as the disease progressed, the ALK gene status of the tumour was investigated, and based upon a positive result, the patient was treated with crizotinib and achieved a complete response.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	40-43
27171126-9	2015	The addition of the c-Met inhibitor crizotinib to the water in which the larvae were kept reduced the migration and proliferation of UM cells expressing c-Met.	Crizotinib	36-46	MET proto-oncogene, receptor tyrosine kinase	Danio rerio	20-25
27171126-9	2015	The addition of the c-Met inhibitor crizotinib to the water in which the larvae were kept reduced the migration and proliferation of UM cells expressing c-Met.	Crizotinib	36-46	MET proto-oncogene, receptor tyrosine kinase	Danio rerio	153-158
25667280-0	2015	Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: results from the EUROS1 cohort.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	58-62
25667280-2	2015	Crizotinib is a potent inhibitor of both ROS1 and ALK kinase domains.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	41-45
25667280-15	2015	CONCLUSION: Crizotinib was highly active at treating lung cancer in patients with a ROS1 rearrangement, suggesting that patients with lung adenocarcinomas should be tested for ROS1.	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	84-88
25667280-15	2015	CONCLUSION: Crizotinib was highly active at treating lung cancer in patients with a ROS1 rearrangement, suggesting that patients with lung adenocarcinomas should be tested for ROS1.	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	176-180
26018277-0	2015	[Therapeutic effects of crizotinib in EML4-ALK-positive patients with non-small-cell lung cancer].	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	43-46
26018277-4	2015	RESULTS: Crizotinib treatment obviously prolonged the PFS in EML4-ALK-positive patients with an objective response rate (OOR) of 61.9% and a median response duration of 16 months, which were significantly better than those in with ALK-negative patients and patients without ALK testing who received different second-line therapies.	Crizotinib	9-19	EMAP like 4	Homo sapiens	61-65
26018277-4	2015	RESULTS: Crizotinib treatment obviously prolonged the PFS in EML4-ALK-positive patients with an objective response rate (OOR) of 61.9% and a median response duration of 16 months, which were significantly better than those in with ALK-negative patients and patients without ALK testing who received different second-line therapies.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	66-69
26018277-4	2015	RESULTS: Crizotinib treatment obviously prolonged the PFS in EML4-ALK-positive patients with an objective response rate (OOR) of 61.9% and a median response duration of 16 months, which were significantly better than those in with ALK-negative patients and patients without ALK testing who received different second-line therapies.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	231-234
26018277-4	2015	RESULTS: Crizotinib treatment obviously prolonged the PFS in EML4-ALK-positive patients with an objective response rate (OOR) of 61.9% and a median response duration of 16 months, which were significantly better than those in with ALK-negative patients and patients without ALK testing who received different second-line therapies.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	231-234
26018277-5	2015	CONCLUSION: Crizotinib is superior to platinum-based chemotherapy in NSCLC patients with ALK rearrangement.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	89-92
25785456-1	2015	Anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) gene rearrangements occur in approximately 5% of non-small-cell lung cancers (NSCLC), leading to the overexpression of anaplastic lymphoma kinase and predicting a response to the targeted inhibitor, crizotinib.	Crizotinib	292-302	EMAP like 4	Homo sapiens	87-91
25785456-1	2015	Anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) gene rearrangements occur in approximately 5% of non-small-cell lung cancers (NSCLC), leading to the overexpression of anaplastic lymphoma kinase and predicting a response to the targeted inhibitor, crizotinib.	Crizotinib	292-302	ALK receptor tyrosine kinase	Homo sapiens	0-26
25785456-1	2015	Anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) gene rearrangements occur in approximately 5% of non-small-cell lung cancers (NSCLC), leading to the overexpression of anaplastic lymphoma kinase and predicting a response to the targeted inhibitor, crizotinib.	Crizotinib	292-302	ALK receptor tyrosine kinase	Homo sapiens	28-31
25785456-1	2015	Anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) gene rearrangements occur in approximately 5% of non-small-cell lung cancers (NSCLC), leading to the overexpression of anaplastic lymphoma kinase and predicting a response to the targeted inhibitor, crizotinib.	Crizotinib	292-302	EMAP like 4	Homo sapiens	37-85
25733882-0	2015	PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations.	Crizotinib	93-103	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	54-58
25733882-0	2015	PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations.	Crizotinib	93-103	ALK receptor tyrosine kinase	Homo sapiens	59-62
25733882-0	2015	PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations.	Crizotinib	93-103	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	114-118
25733882-2	2015	The MET/ALK/ROS1 inhibitor crizotinib (Xalkori, PF-02341066) has demonstrated promising clinical activity in ROS1 fusion-positive non-small cell lung cancer.	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	8-11
25733882-2	2015	The MET/ALK/ROS1 inhibitor crizotinib (Xalkori, PF-02341066) has demonstrated promising clinical activity in ROS1 fusion-positive non-small cell lung cancer.	Crizotinib	27-37	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	12-16
25733882-2	2015	The MET/ALK/ROS1 inhibitor crizotinib (Xalkori, PF-02341066) has demonstrated promising clinical activity in ROS1 fusion-positive non-small cell lung cancer.	Crizotinib	27-37	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	109-113
25733882-5	2015	In vitro, PF-06463922 exhibited subnanomolar cellular potency against oncogenic ROS1 fusions and inhibited the crizotinib-refractory ROS1(G2032R) mutation and the ROS1(G2026M) gatekeeper mutation.	Crizotinib	111-121	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	133-137
25733882-5	2015	In vitro, PF-06463922 exhibited subnanomolar cellular potency against oncogenic ROS1 fusions and inhibited the crizotinib-refractory ROS1(G2032R) mutation and the ROS1(G2026M) gatekeeper mutation.	Crizotinib	111-121	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	133-137
25733882-10	2015	Taken together, our results indicate that PF-06463922 has potential for treating ROS1 fusion-positive cancers, including those requiring agents with CNS-penetrating properties, as well as for overcoming crizotinib resistance driven by ROS1 mutation.	Crizotinib	203-213	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	235-239
25691052-2	2015	Although high response rates and disease control have been observed in lung cancer patients bearing rearranged ROS1 tumors (ROS1+) treated with the kinase inhibitor crizotinib, many of these patients eventually relapse.To identify mechanisms of resistance to ROS1 inhibitors we generated resistant cells from HCC78 lung cancer cells bearing the SLC34A2-ROS1 rearrangement.	Crizotinib	165-175	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	111-115
25691052-2	2015	Although high response rates and disease control have been observed in lung cancer patients bearing rearranged ROS1 tumors (ROS1+) treated with the kinase inhibitor crizotinib, many of these patients eventually relapse.To identify mechanisms of resistance to ROS1 inhibitors we generated resistant cells from HCC78 lung cancer cells bearing the SLC34A2-ROS1 rearrangement.	Crizotinib	165-175	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	124-128
25691052-2	2015	Although high response rates and disease control have been observed in lung cancer patients bearing rearranged ROS1 tumors (ROS1+) treated with the kinase inhibitor crizotinib, many of these patients eventually relapse.To identify mechanisms of resistance to ROS1 inhibitors we generated resistant cells from HCC78 lung cancer cells bearing the SLC34A2-ROS1 rearrangement.	Crizotinib	165-175	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	124-128
25691052-5	2015	Interestingly, we identified focal KRAS amplification in a biopsy of a tumor from a patient that had become resistant to crizotinib treatment.Altogether our data suggest that the activation of members of the RAS family can confer resistance to ROS1 inhibitors.	Crizotinib	121-131	KRAS proto-oncogene, GTPase	Homo sapiens	35-39
25691052-5	2015	Interestingly, we identified focal KRAS amplification in a biopsy of a tumor from a patient that had become resistant to crizotinib treatment.Altogether our data suggest that the activation of members of the RAS family can confer resistance to ROS1 inhibitors.	Crizotinib	121-131	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	244-248
25759024-6	2015	We observed enrichment of gene signatures associated with several resistance drivers (including P2Y receptors) in crizotinib-resistant ALK-rearranged lung tumors compared to treatment-naive controls, supporting a role for these identified mechanisms in clinical ALK inhibitor resistance.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	135-138
25759024-6	2015	We observed enrichment of gene signatures associated with several resistance drivers (including P2Y receptors) in crizotinib-resistant ALK-rearranged lung tumors compared to treatment-naive controls, supporting a role for these identified mechanisms in clinical ALK inhibitor resistance.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	262-265
26819719-0	2015	Correlation of plasma crizotinib trough concentration with adverse events in patients with anaplastic lymphoma kinase positive non-small-cell lung cancer.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	91-117
26819719-1	2015	BACKGROUND: Crizotinib, an ATP-competitive receptor tyrosine kinase inhibitor of both anaplastic lymphoma kinase (ALK) and the hepatocyte growth factor receptor, commonly causes several adverse events (AEs).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	86-112
26819719-1	2015	BACKGROUND: Crizotinib, an ATP-competitive receptor tyrosine kinase inhibitor of both anaplastic lymphoma kinase (ALK) and the hepatocyte growth factor receptor, commonly causes several adverse events (AEs).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	114-117
26819719-1	2015	BACKGROUND: Crizotinib, an ATP-competitive receptor tyrosine kinase inhibitor of both anaplastic lymphoma kinase (ALK) and the hepatocyte growth factor receptor, commonly causes several adverse events (AEs).	Crizotinib	12-22	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	127-160
26629283-0	2015	Zykadia (Ceritinib) Approved for Patients with Crizotinib-Resistant ALK -Positive Non-Small-Cell Lung Cancer.	Crizotinib	47-57	ALK receptor tyrosine kinase	Homo sapiens	68-71
25581823-3	2015	In this study, we found that the lung adenocarcinoma cell line A925L expresses an EML4-ALK gene fusion (variant 5a, E2:A20) and is sensitive to the ALK inhibitors crizotinib and alectinib.	Crizotinib	163-173	EMAP like 4	Homo sapiens	82-86
25581823-3	2015	In this study, we found that the lung adenocarcinoma cell line A925L expresses an EML4-ALK gene fusion (variant 5a, E2:A20) and is sensitive to the ALK inhibitors crizotinib and alectinib.	Crizotinib	163-173	ALK receptor tyrosine kinase	Homo sapiens	148-151
25766836-0	2015	Crizotinib resistance in acute myeloid leukemia with inv(2)(p23q13)/RAN binding protein 2 (RANBP2) anaplastic lymphoma kinase (ALK) fusion and monosomy 7.	Crizotinib	0-10	RAN binding protein 2	Homo sapiens	68-89
25766836-0	2015	Crizotinib resistance in acute myeloid leukemia with inv(2)(p23q13)/RAN binding protein 2 (RANBP2) anaplastic lymphoma kinase (ALK) fusion and monosomy 7.	Crizotinib	0-10	RAN binding protein 2	Homo sapiens	91-97
25766836-0	2015	Crizotinib resistance in acute myeloid leukemia with inv(2)(p23q13)/RAN binding protein 2 (RANBP2) anaplastic lymphoma kinase (ALK) fusion and monosomy 7.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	99-125
25766836-0	2015	Crizotinib resistance in acute myeloid leukemia with inv(2)(p23q13)/RAN binding protein 2 (RANBP2) anaplastic lymphoma kinase (ALK) fusion and monosomy 7.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	127-130
25766836-1	2015	This is the first report on the development of a p.G1269A mutation within the kinase domain (KD) of ALK after crizotinib treatment in RANBP2-ALK acute myeloid leukemia (AML).	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	100-103
25766836-2	2015	An elderly woman with AML with an inv(2)(p23q13)/RANBP2-ALK and monosomy 7 was treated with crizotinib.	Crizotinib	92-102	RAN binding protein 2	Homo sapiens	49-55
25766836-2	2015	An elderly woman with AML with an inv(2)(p23q13)/RANBP2-ALK and monosomy 7 was treated with crizotinib.	Crizotinib	92-102	ALK receptor tyrosine kinase	Homo sapiens	56-59
25458559-3	2015	The accelerated approval of potent ALK inhibitors, such as crizotinib and more recently ceritinib (LDK378), based on the well designed phase I/II trials has been a landmark success in clinical cancer research and contributes a new era of oncogenic targeted therapy characterized by elegant clinical trial design.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	35-38
25749034-2	2015	Crizotinib (XalkoriTM), a potent ALK inhibitor, represents the current front-line treatment for ALK+ NSCLC and shows great clinical efficacy.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	33-36
25749034-2	2015	Crizotinib (XalkoriTM), a potent ALK inhibitor, represents the current front-line treatment for ALK+ NSCLC and shows great clinical efficacy.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	96-99
25749034-4	2015	ASP3026 is a novel second-generation ALK inhibitor with activity on crizotinib-resistant ALK-L1196M gatekeeper mutant.	Crizotinib	68-78	ALK receptor tyrosine kinase	Homo sapiens	37-40
25749034-4	2015	ASP3026 is a novel second-generation ALK inhibitor with activity on crizotinib-resistant ALK-L1196M gatekeeper mutant.	Crizotinib	68-78	ALK receptor tyrosine kinase	Homo sapiens	89-92
25653133-1	2015	New protocols based on ALK-targeted therapy by crizotinib or other ALK-targeting molecules have opened for the treatment of patients with neuroblastoma (NB) if their tumors showed mutation and/or amplification of the ALK gene.	Crizotinib	47-57	ALK receptor tyrosine kinase	Homo sapiens	23-26
25588040-1	2015	PURPOSE OF REVIEW: Crizotinib now is accepted as the standard first-line treatment of ALK-rearranged lung adenocarcinomas.	Crizotinib	19-29	ALK receptor tyrosine kinase	Homo sapiens	86-89
25588040-2	2015	To overcome the problem of crizotinib resistance, second-generation ALK inhibitors are in development.	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	68-71
25588040-4	2015	RECENT FINDINGS: Based on phase I/II data, ceritinib has gained accelerated FDA approval for the treatment of crizotinib-resistant ALK-rearranged lung cancer.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	131-134
25876560-2	2015	In particular, the outcomes of patients with advanced NSCLC driven by the EML4-ALK fusion protein, which comprise 3-5% of cases, have remarkably improved with the use of crizotinib, an oral multi-tyrosine kinase inhibitor that targets ALK.	Crizotinib	170-180	EMAP like 4	Homo sapiens	74-78
25876560-2	2015	In particular, the outcomes of patients with advanced NSCLC driven by the EML4-ALK fusion protein, which comprise 3-5% of cases, have remarkably improved with the use of crizotinib, an oral multi-tyrosine kinase inhibitor that targets ALK.	Crizotinib	170-180	ALK receptor tyrosine kinase	Homo sapiens	79-82
25876560-2	2015	In particular, the outcomes of patients with advanced NSCLC driven by the EML4-ALK fusion protein, which comprise 3-5% of cases, have remarkably improved with the use of crizotinib, an oral multi-tyrosine kinase inhibitor that targets ALK.	Crizotinib	170-180	ALK receptor tyrosine kinase	Homo sapiens	235-238
25876560-5	2015	Preclinical studies have shown that it is also active against several mutant forms of ALK that confer resistance to crizotinib, including the gatekeeper mutation L1196M.	Crizotinib	116-126	ALK receptor tyrosine kinase	Homo sapiens	86-89
25659177-0	2015	A safety assessment of crizotinib in the treatment of ALK-positive NSCLC patients.	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	54-57
25659177-2	2015	Crizotinib has been shown to be an inhibitor of MET, anaplastic lymphoma kinase (ALK) and ROS1 receptor tyrosine kinases, and is FDA approved for ALK inhibition.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	53-79
25659177-2	2015	Crizotinib has been shown to be an inhibitor of MET, anaplastic lymphoma kinase (ALK) and ROS1 receptor tyrosine kinases, and is FDA approved for ALK inhibition.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	81-84
25659177-2	2015	Crizotinib has been shown to be an inhibitor of MET, anaplastic lymphoma kinase (ALK) and ROS1 receptor tyrosine kinases, and is FDA approved for ALK inhibition.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	90-94
25659177-2	2015	Crizotinib has been shown to be an inhibitor of MET, anaplastic lymphoma kinase (ALK) and ROS1 receptor tyrosine kinases, and is FDA approved for ALK inhibition.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	146-149
25659177-3	2015	Crizotinib is effective in NSCLC that harbors ALK translocations resulting in overexpression of oncogenic ALK fusion proteins.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	46-49
25659177-3	2015	Crizotinib is effective in NSCLC that harbors ALK translocations resulting in overexpression of oncogenic ALK fusion proteins.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	106-109
25659177-4	2015	AREAS COVERED: This paper will review crizotinib as a treatment for ALK-positive NSCLC.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	68-71
25659177-6	2015	EXPERT OPINION: Compared to standard chemotherapy, crizotinib shows improved progression-free survival in ALK-positive NSCLC, with patient"s reporting improved quality of life.	Crizotinib	51-61	ALK receptor tyrosine kinase	Homo sapiens	106-109
25659177-9	2015	Many, though not all, of these side effects are likely due to the multiple tyrosine kinases inhibited by crizotinib, and will likely improve with second- and third-generation inhibitors that inhibit ALK more specifically.	Crizotinib	105-115	ALK receptor tyrosine kinase	Homo sapiens	199-202
26045865-1	2015	EML4-ALK rearrangement is detected in 2% to 7% of lung adenocarcinomas, these tumors are sensitive to crizotinib.	Crizotinib	102-112	ALK receptor tyrosine kinase	Homo sapiens	5-8
25502629-1	2015	Non-small cell lung cancer (NSCLC) carrying echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements is hypersensitive to ALK inhibitors, including crizotinib and alectinib.	Crizotinib	195-205	EMAP like 4	Homo sapiens	44-92
25502629-1	2015	Non-small cell lung cancer (NSCLC) carrying echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements is hypersensitive to ALK inhibitors, including crizotinib and alectinib.	Crizotinib	195-205	EMAP like 4	Homo sapiens	94-98
25502629-1	2015	Non-small cell lung cancer (NSCLC) carrying echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements is hypersensitive to ALK inhibitors, including crizotinib and alectinib.	Crizotinib	195-205	ALK receptor tyrosine kinase	Homo sapiens	128-131
25502629-1	2015	Non-small cell lung cancer (NSCLC) carrying echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements is hypersensitive to ALK inhibitors, including crizotinib and alectinib.	Crizotinib	195-205	ALK receptor tyrosine kinase	Homo sapiens	169-172
25695223-0	2015	Analysis of ERBB ligand-induced resistance mechanism to crizotinib by primary culture of lung adenocarcinoma with EML4-ALK fusion gene.	Crizotinib	56-66	epidermal growth factor receptor	Homo sapiens	12-16
25695223-0	2015	Analysis of ERBB ligand-induced resistance mechanism to crizotinib by primary culture of lung adenocarcinoma with EML4-ALK fusion gene.	Crizotinib	56-66	EMAP like 4	Homo sapiens	114-118
25695223-0	2015	Analysis of ERBB ligand-induced resistance mechanism to crizotinib by primary culture of lung adenocarcinoma with EML4-ALK fusion gene.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	119-122
25695223-1	2015	INTRODUCTION: Using cell line-based assays, the secretion of erythroblastic leukemia viral oncogene homologue (ERBB) ligands has been reported to contribute to resistance against crizotinib in lung cancer with the echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase fusion gene.	Crizotinib	179-189	epidermal growth factor receptor	Homo sapiens	111-115
25695223-1	2015	INTRODUCTION: Using cell line-based assays, the secretion of erythroblastic leukemia viral oncogene homologue (ERBB) ligands has been reported to contribute to resistance against crizotinib in lung cancer with the echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase fusion gene.	Crizotinib	179-189	EMAP like 4	Homo sapiens	214-262
25695223-12	2015	CONCLUSION: Stimulation by ERBB ligands is suggested to be responsible for resistance to crizotinib in this patient.	Crizotinib	89-99	epidermal growth factor receptor	Homo sapiens	27-31
25922742-0	2015	Anaplastic lymphoma kinase-positive lung adenocarcinoma patient with development of sick sinus syndrome while on targeted treatment with crizotinib.	Crizotinib	137-147	ALK receptor tyrosine kinase	Homo sapiens	0-26
25922742-2	2015	Crizotinib as an ALK inhibitor has been used in treating ALK positive NSCLC patients for several years and some adverse effects should be paid attention to.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	17-20
25922742-2	2015	Crizotinib as an ALK inhibitor has been used in treating ALK positive NSCLC patients for several years and some adverse effects should be paid attention to.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	57-60
25922742-3	2015	We now describe a case of ALK positive NSCLC patient with development of sick sinus syndrome (SSS) while on targeted treatment with crizotinib.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	26-29
25601484-3	2015	Crizotinib was the first ALK-TKI to undergo clinical development in ALK-positive advanced NSCLC, in which it has been shown to greatly outperform the best available chemotherapy regimen in either second- or first-line setting.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	25-28
25601484-3	2015	Crizotinib was the first ALK-TKI to undergo clinical development in ALK-positive advanced NSCLC, in which it has been shown to greatly outperform the best available chemotherapy regimen in either second- or first-line setting.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	68-71
25601484-4	2015	More recently, the novel second-generation ALK-TKI ceritinib has been shown to be highly active in either crizotinib-pretreated or -naive population.	Crizotinib	106-116	ALK receptor tyrosine kinase	Homo sapiens	43-46
24662823-11	2015	Gene expression analysis using CCLE database shows that cancer cells with high levels of FGFR and integrin beta3 are resistant to crizotinib treatment, suggesting that FGFR and integrin beta3 could be used as predictive markers for Met-targeted therapy and provide a potential therapeutic option to overcome acquired and innate resistance for the Met-targeting drugs.	Crizotinib	130-140	integrin subunit beta 3	Homo sapiens	98-112
24662823-11	2015	Gene expression analysis using CCLE database shows that cancer cells with high levels of FGFR and integrin beta3 are resistant to crizotinib treatment, suggesting that FGFR and integrin beta3 could be used as predictive markers for Met-targeted therapy and provide a potential therapeutic option to overcome acquired and innate resistance for the Met-targeting drugs.	Crizotinib	130-140	integrin subunit beta 3	Homo sapiens	177-191
25889062-6	2015	To the best of our knowledge, this is the first case report of surgical resection in ALK rearrangement-positive lung adenocarcinoma after crizotinib treatment.	Crizotinib	138-148	ALK receptor tyrosine kinase	Homo sapiens	85-88
25564153-2	2015	Among the notable successes have been the approval of erlotinib, gefitinib, and afatinib for the EGFR mutation, and more recently crizotinib for anaplastic lymphoma kinase (ALK) gene rearrangement.	Crizotinib	130-140	ALK receptor tyrosine kinase	Homo sapiens	173-176
25671264-0	2015	Crizotinib in ROS1-rearranged non-small-cell lung cancer.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	14-18
24616318-0	2015	Optic neuropathy and blindness associated with crizotinib for non-small-cell lung cancer with EML4-ALK translocation.	Crizotinib	47-57	EMAP like 4	Homo sapiens	94-98
24616318-0	2015	Optic neuropathy and blindness associated with crizotinib for non-small-cell lung cancer with EML4-ALK translocation.	Crizotinib	47-57	ALK receptor tyrosine kinase	Homo sapiens	99-102
25678804-0	2015	Novel covalent modification of human anaplastic lymphoma kinase (ALK) and potentiation of crizotinib-mediated inhibition of ALK activity by BNP7787.	Crizotinib	90-100	ALK receptor tyrosine kinase	Homo sapiens	124-127
25678804-10	2015	Additionally, in vitro kinase activity assays indicate that BNP7787 inhibits ALK catalytic activity and potentiates the activity of the ALK-targeted drug crizotinib.	Crizotinib	154-164	ALK receptor tyrosine kinase	Homo sapiens	136-139
25403583-10	2015	However, eight patients who received ALK inhibitor (crizotinib or ceritinib) showed good response, with response rate of 87.5% (7/8 with partial response) and durable progression-free survival.	Crizotinib	52-62	ALK receptor tyrosine kinase	Homo sapiens	37-40
25529354-11	2015	One of the 2 ALK IHC-positive cases also demonstrated a positive result in the RT-PCR assay and the patient benefited from crizotinib treatment.	Crizotinib	123-133	ALK receptor tyrosine kinase	Homo sapiens	13-16
25656857-3	2015	The intracranial efficacy of targeted therapies (EGFR tyrosine kinase inhibitors, ALK inhibitors) is demonstrated, and is globally superior to the efficacy of standard chemotherapy, justifying their use as front-line therapy in case of EGFR activating mutation or ALK rearrangement (providing the change in the crizotinib label in France).	Crizotinib	311-321	epidermal growth factor receptor	Homo sapiens	49-53
25656857-3	2015	The intracranial efficacy of targeted therapies (EGFR tyrosine kinase inhibitors, ALK inhibitors) is demonstrated, and is globally superior to the efficacy of standard chemotherapy, justifying their use as front-line therapy in case of EGFR activating mutation or ALK rearrangement (providing the change in the crizotinib label in France).	Crizotinib	311-321	ALK receptor tyrosine kinase	Homo sapiens	82-85
25413260-0	2015	ALK-rearranged non-small cell lung cancers: how best to optimize the safety of crizotinib in clinical practice?	Crizotinib	79-89	ALK receptor tyrosine kinase	Homo sapiens	0-3
25413260-1	2015	Crizotinib (XALKORI , Pfizer) is a tyrosine kinase inhibitor targeting ALK, MET and ROS1, currently approved for the treatment of adults with ALK-rearranged non-small-cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	13-16
25413260-1	2015	Crizotinib (XALKORI , Pfizer) is a tyrosine kinase inhibitor targeting ALK, MET and ROS1, currently approved for the treatment of adults with ALK-rearranged non-small-cell lung cancer.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	84-88
25413260-1	2015	Crizotinib (XALKORI , Pfizer) is a tyrosine kinase inhibitor targeting ALK, MET and ROS1, currently approved for the treatment of adults with ALK-rearranged non-small-cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	71-74
26040108-2	2015	The main target for the crizotinib is anaplastic lymphoma kinase (ALK).	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	66-69
26040108-3	2015	Evidences available indicate that double mutant ALK (L1196M and G1269A) confers resistance to crizotinib.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	48-51
26040108-5	2015	Hence, in the present study, molecular dynamic (MD) simulation approach was employed to study the impact of crizotinib binding efficacy with ALK structures at a molecular level.	Crizotinib	108-118	ALK receptor tyrosine kinase	Homo sapiens	141-144
26040108-6	2015	Docking results indicated that ALK double mutant (L1196M and G1269A) significantly affected the binding affinity for crizotinib.	Crizotinib	117-127	ALK receptor tyrosine kinase	Homo sapiens	31-34
26040108-7	2015	Furthermore, MD studies revealed that mutant ALK-crizotinib complex showed higher deviation, higher fluctuation and decreased number of intermolecular H-bonds, when compared to the native ALK-crizotinib complex.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	45-48
26040108-7	2015	Furthermore, MD studies revealed that mutant ALK-crizotinib complex showed higher deviation, higher fluctuation and decreased number of intermolecular H-bonds, when compared to the native ALK-crizotinib complex.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	188-191
26040108-7	2015	Furthermore, MD studies revealed that mutant ALK-crizotinib complex showed higher deviation, higher fluctuation and decreased number of intermolecular H-bonds, when compared to the native ALK-crizotinib complex.	Crizotinib	192-202	ALK receptor tyrosine kinase	Homo sapiens	45-48
26040108-7	2015	Furthermore, MD studies revealed that mutant ALK-crizotinib complex showed higher deviation, higher fluctuation and decreased number of intermolecular H-bonds, when compared to the native ALK-crizotinib complex.	Crizotinib	192-202	ALK receptor tyrosine kinase	Homo sapiens	188-191
25973127-1	2015	ALK rearrangement is a very rare subset of squamous cell cancer of lung and the efficacy of crizotinib treatment for these patients is lack of data.	Crizotinib	92-102	ALK receptor tyrosine kinase	Homo sapiens	0-3
25973127-2	2015	Here we report a case with squamous cell cancer of lung that harbored the ALK rearrangement was given crizotinib in the second-line therapy.	Crizotinib	102-112	ALK receptor tyrosine kinase	Homo sapiens	74-77
25757678-2	2015	Crizotinib is a small-molecule oral inhibitor of ALK, c-Met/HGF receptor and ROS1 receptor kinases.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	49-52
25671265-0	2015	Crizotinib in ROS1-rearranged non-small-cell lung cancer.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	14-18
25558789-0	2015	Choroidal metastasis response to crizotinib in a ROS1-rearranged NSCLC patient.	Crizotinib	33-43	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	49-53
25558789-3	2015	Recently, there are several case reports of choroidal metastases in patients with anaplastic lymphoma kinase (ALK)-driven NSCLC one of which the patient"s choroidal metastases had responded to crizotinib, multi-targeted tyrosine kinase inhibitor against ALK/ROS1/MET.	Crizotinib	193-203	ALK receptor tyrosine kinase	Homo sapiens	82-108
25558789-3	2015	Recently, there are several case reports of choroidal metastases in patients with anaplastic lymphoma kinase (ALK)-driven NSCLC one of which the patient"s choroidal metastases had responded to crizotinib, multi-targeted tyrosine kinase inhibitor against ALK/ROS1/MET.	Crizotinib	193-203	ALK receptor tyrosine kinase	Homo sapiens	110-113
25558789-3	2015	Recently, there are several case reports of choroidal metastases in patients with anaplastic lymphoma kinase (ALK)-driven NSCLC one of which the patient"s choroidal metastases had responded to crizotinib, multi-targeted tyrosine kinase inhibitor against ALK/ROS1/MET.	Crizotinib	193-203	ALK receptor tyrosine kinase	Homo sapiens	254-257
25558789-3	2015	Recently, there are several case reports of choroidal metastases in patients with anaplastic lymphoma kinase (ALK)-driven NSCLC one of which the patient"s choroidal metastases had responded to crizotinib, multi-targeted tyrosine kinase inhibitor against ALK/ROS1/MET.	Crizotinib	193-203	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	258-262
25558789-4	2015	Similarly ROS1-rearranged NSCLC has very similar clinicopathologic characteristics as ALK-rearranged NSCLC and crizotinib has demonstrated significant clinical activity against ROS1-rearranged NSCLC.	Crizotinib	111-121	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	177-181
25558789-5	2015	MATERIALS AND METHODS: Here in this report we presented a patient with ROS1-rearranged NSCLC that presented with choroidal metastases that did not respond to initial chemotherapy but had a rapid and complete response to crizotinib.	Crizotinib	220-230	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	71-75
25558789-6	2015	CONCLUSIONS: Although likely to be exceeding rare, choroidal metastases from ROS1-rearranged NSCLC can be successfully treated with crizotinib similar to choroidal metastases from ALK-rearranged NSCLC can be successfully treated from another case report.	Crizotinib	132-142	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	77-81
25576294-0	2015	Management of crizotinib therapy for ALK-rearranged non-small cell lung carcinoma: an expert consensus.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	37-40
25576294-1	2015	Within 4 years of the discovery of anaplastic lymphoma kinase (ALK) rearrangements in non-small cell lung cancer (NSCLC), the ALK inhibitor crizotinib gained US and European approval for the treatment of advanced ALK-positive NSCLC.	Crizotinib	140-150	ALK receptor tyrosine kinase	Homo sapiens	35-61
25576294-1	2015	Within 4 years of the discovery of anaplastic lymphoma kinase (ALK) rearrangements in non-small cell lung cancer (NSCLC), the ALK inhibitor crizotinib gained US and European approval for the treatment of advanced ALK-positive NSCLC.	Crizotinib	140-150	ALK receptor tyrosine kinase	Homo sapiens	63-66
25576294-1	2015	Within 4 years of the discovery of anaplastic lymphoma kinase (ALK) rearrangements in non-small cell lung cancer (NSCLC), the ALK inhibitor crizotinib gained US and European approval for the treatment of advanced ALK-positive NSCLC.	Crizotinib	140-150	ALK receptor tyrosine kinase	Homo sapiens	126-129
25576294-1	2015	Within 4 years of the discovery of anaplastic lymphoma kinase (ALK) rearrangements in non-small cell lung cancer (NSCLC), the ALK inhibitor crizotinib gained US and European approval for the treatment of advanced ALK-positive NSCLC.	Crizotinib	140-150	ALK receptor tyrosine kinase	Homo sapiens	126-129
25576294-2	2015	This was due to the striking response data observed with crizotinib in phase I and II trials in patients with ALK-positive NSCLC, as well as the favorable tolerability and safety profile observed.	Crizotinib	57-67	ALK receptor tyrosine kinase	Homo sapiens	110-113
25526238-4	2015	All patients had previously been treated with both FDA-approved ALK inhibitors--crizotinib and ceritinib.	Crizotinib	80-90	ALK receptor tyrosine kinase	Homo sapiens	64-67
25556163-1	2015	Crizotinib is a potent and specific small-molecule inhibitor of both anaplastic lymphoma kinase (ALK) and c-MET tyrosine kinases, and patients with ALK rearrangement tumor benefit from crizotinib treatment; however, its penetration into calculated cerebrospinal fluid (CSF) is considered to be poor.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	69-95
25556163-1	2015	Crizotinib is a potent and specific small-molecule inhibitor of both anaplastic lymphoma kinase (ALK) and c-MET tyrosine kinases, and patients with ALK rearrangement tumor benefit from crizotinib treatment; however, its penetration into calculated cerebrospinal fluid (CSF) is considered to be poor.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	97-100
25556163-1	2015	Crizotinib is a potent and specific small-molecule inhibitor of both anaplastic lymphoma kinase (ALK) and c-MET tyrosine kinases, and patients with ALK rearrangement tumor benefit from crizotinib treatment; however, its penetration into calculated cerebrospinal fluid (CSF) is considered to be poor.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	148-151
25556163-1	2015	Crizotinib is a potent and specific small-molecule inhibitor of both anaplastic lymphoma kinase (ALK) and c-MET tyrosine kinases, and patients with ALK rearrangement tumor benefit from crizotinib treatment; however, its penetration into calculated cerebrospinal fluid (CSF) is considered to be poor.	Crizotinib	185-195	ALK receptor tyrosine kinase	Homo sapiens	148-151
27490033-0	2015	Computational Investigation and Experimental Validation of Crizotinib Resistance Conferred by C1156Y Mutant Anaplastic Lymphoma Kinase.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	108-134
27490033-2	2015	The main target for crizotinib was anaplastic lymphoma kinase (ALK).	Crizotinib	20-30	ALK receptor tyrosine kinase	Homo sapiens	35-61
27490033-2	2015	The main target for crizotinib was anaplastic lymphoma kinase (ALK).	Crizotinib	20-30	ALK receptor tyrosine kinase	Homo sapiens	63-66
27490033-3	2015	However, evidences available indicate that C1156Y mutation in ALK confers resistance to crizotinib.	Crizotinib	88-98	ALK receptor tyrosine kinase	Homo sapiens	62-65
27490033-5	2015	Hence, in the present study computational approaches have been employed alongside KINOMEscan profiling technique to reveal the mechanism behind crizotinib resistance in ALK at a molecular level.	Crizotinib	144-154	ALK receptor tyrosine kinase	Homo sapiens	169-172
27490033-6	2015	The results of our analysis indicate that C1156Y mutation alters the conformation of the ALK binding pocket residues which results in a marked decrease in hydrogen bond interactions between crizotinib and ALK.	Crizotinib	190-200	ALK receptor tyrosine kinase	Homo sapiens	89-92
27490033-6	2015	The results of our analysis indicate that C1156Y mutation alters the conformation of the ALK binding pocket residues which results in a marked decrease in hydrogen bond interactions between crizotinib and ALK.	Crizotinib	190-200	ALK receptor tyrosine kinase	Homo sapiens	205-208
25592111-0	2015	Synergistic effects of crizotinib and radiotherapy in experimental EML4-ALK fusion positive lung cancer.	Crizotinib	23-33	EMAP like 4	Homo sapiens	67-71
25592111-0	2015	Synergistic effects of crizotinib and radiotherapy in experimental EML4-ALK fusion positive lung cancer.	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	72-75
25592111-1	2015	BACKGROUND AND PURPOSE: Non-small cell lung cancer (NSCLC) patients with chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) are sensitive to the tyrosine kinase inhibitor crizotinib.	Crizotinib	192-202	ALK receptor tyrosine kinase	Homo sapiens	107-138
25592111-1	2015	BACKGROUND AND PURPOSE: Non-small cell lung cancer (NSCLC) patients with chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) are sensitive to the tyrosine kinase inhibitor crizotinib.	Crizotinib	192-202	ALK receptor tyrosine kinase	Homo sapiens	140-143
25592111-2	2015	We aimed to investigate the effects of combined radiotherapy and crizotinib in ALK-positive vs. wild type NSCLC models.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	79-82
25592111-6	2015	RESULTS: Crizotinib exerted potent and selective anti-proliferative and pro-apoptotic effects in ALK+ H3122 cells which were augmented by radiotherapy.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	97-100
25592111-11	2015	CONCLUSIONS: Crizotinib elicits beneficial effects in combination with radiotherapy only in ALK-positive NSCLC.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	92-95
25806340-3	2015	ALK+ NSCLCs can be treated with the dual ALK/MET inhibitor crizotinib, with better outcome compared to standard chemotherapy.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	0-3
25806340-5	2015	Point mutations within the ALK catalytic domain or ALK gene amplification account for approximately 30-40% of crizotinib-resistant cases, suggesting that the diseases still relies on ALK activity and that more potent inhibitors could be useful in this setting.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	27-30
25806340-5	2015	Point mutations within the ALK catalytic domain or ALK gene amplification account for approximately 30-40% of crizotinib-resistant cases, suggesting that the diseases still relies on ALK activity and that more potent inhibitors could be useful in this setting.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	51-54
25806340-5	2015	Point mutations within the ALK catalytic domain or ALK gene amplification account for approximately 30-40% of crizotinib-resistant cases, suggesting that the diseases still relies on ALK activity and that more potent inhibitors could be useful in this setting.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	51-54
25806340-6	2015	Ceritinib is a novel selective ALK inhibitor with preclinical activity against crizotinib-resistant ALK mutants.	Crizotinib	79-89	ALK receptor tyrosine kinase	Homo sapiens	31-34
25806340-6	2015	Ceritinib is a novel selective ALK inhibitor with preclinical activity against crizotinib-resistant ALK mutants.	Crizotinib	79-89	ALK receptor tyrosine kinase	Homo sapiens	100-103
25676398-0	2015	[Treatment of patients with ALK gene rearranged non-small cell lung cancer  : after resistance to crizotinib].	Crizotinib	98-108	ALK receptor tyrosine kinase	Homo sapiens	28-31
25676398-8	2015	We will focus on the mechanism of first generation ALK TKI (crizotinib) resistance in patients with ALK positive NSCLC.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	51-54
25676398-8	2015	We will focus on the mechanism of first generation ALK TKI (crizotinib) resistance in patients with ALK positive NSCLC.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	100-103
25676398-9	2015	Likewise, we will also discuss the current therapies for ALK positive NSCLC patients after crizotinib resistance.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	57-60
25676401-0	2015	[Crizotinib treatment in a lung adenocarcinoma harboring ALK fusion gene with bone marrow metastasis: case report and literature review].	Crizotinib	1-11	ALK receptor tyrosine kinase	Homo sapiens	57-60
25676401-2	2015	Crizotinib had been confirmed to be used in anaplastic lymphoma kinase (ALK) positive lung adenocarcinoma, but the efficacy in lung cancer with bone marrow metastasis was unknown.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	44-70
25676401-2	2015	Crizotinib had been confirmed to be used in anaplastic lymphoma kinase (ALK) positive lung adenocarcinoma, but the efficacy in lung cancer with bone marrow metastasis was unknown.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	72-75
25676401-3	2015	In the present study, we reported one case of ALK-positive lung adenocarcinoma with bone marrow matastasis given crizotinib treatment, the safety and efficacy was summarized.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	46-49
25759656-0	2015	A case of orbital metastasis as disease progression of anaplastic lymphoma kinase-positive lung cancer treated with crizotinib.	Crizotinib	116-126	ALK receptor tyrosine kinase	Homo sapiens	55-81
25759656-4	2015	Crizotinib is an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor that leads to responses in most patients with ALK-positive non-small-cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	17-43
25759656-4	2015	Crizotinib is an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor that leads to responses in most patients with ALK-positive non-small-cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	45-48
25759656-4	2015	Crizotinib is an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor that leads to responses in most patients with ALK-positive non-small-cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	122-125
25759656-7	2015	It should be kept in mind that orbital metastasis can be the disease progression of lung adenocarcinoma with ALK translocation treated with crizotinib.	Crizotinib	140-150	ALK receptor tyrosine kinase	Homo sapiens	109-112
26579422-2	2015	The first generation ALK inhibitor crizotinib was granted US FDA approval with only four years of preclinical and clinical testing.	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	21-24
25344360-1	2015	BACKGROUND: Patients with advanced lung adenocarcinomas expressing ALK rearrangements are highly responsive to crizotinib, a dual ALK/c-MET inhibitor.	Crizotinib	111-121	ALK receptor tyrosine kinase	Homo sapiens	67-70
25344360-1	2015	BACKGROUND: Patients with advanced lung adenocarcinomas expressing ALK rearrangements are highly responsive to crizotinib, a dual ALK/c-MET inhibitor.	Crizotinib	111-121	ALK receptor tyrosine kinase	Homo sapiens	130-133
25344360-1	2015	BACKGROUND: Patients with advanced lung adenocarcinomas expressing ALK rearrangements are highly responsive to crizotinib, a dual ALK/c-MET inhibitor.	Crizotinib	111-121	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	134-139
25344360-2	2015	Immunohistochemistry (IHC) is an easy clinically and routinely applicable cost-effective assay for ALK, c-MET and ROS1 protein expression for potential treatment with crizotinib.	Crizotinib	167-177	ALK receptor tyrosine kinase	Homo sapiens	99-102
25344360-2	2015	Immunohistochemistry (IHC) is an easy clinically and routinely applicable cost-effective assay for ALK, c-MET and ROS1 protein expression for potential treatment with crizotinib.	Crizotinib	167-177	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	104-109
25344360-2	2015	Immunohistochemistry (IHC) is an easy clinically and routinely applicable cost-effective assay for ALK, c-MET and ROS1 protein expression for potential treatment with crizotinib.	Crizotinib	167-177	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	114-118
26107243-0	2015	A Pooled Analysis on Crizotinib in Treating Chinese Patients with EML4-ALK Positive Non-small-cell Lung Cancer.	Crizotinib	21-31	EMAP like 4	Homo sapiens	66-70
26107243-0	2015	A Pooled Analysis on Crizotinib in Treating Chinese Patients with EML4-ALK Positive Non-small-cell Lung Cancer.	Crizotinib	21-31	ALK receptor tyrosine kinase	Homo sapiens	71-74
26107243-1	2015	BACKGROUND: This analysis was conducted to evaluate the efficacy and safety of crizotinib based regimens in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer.	Crizotinib	79-89	EMAP like 4	Homo sapiens	139-143
26107243-1	2015	BACKGROUND: This analysis was conducted to evaluate the efficacy and safety of crizotinib based regimens in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer.	Crizotinib	79-89	ALK receptor tyrosine kinase	Homo sapiens	144-147
26107243-2	2015	MATERIALS AND METHODS: Clinical studies evaluating the efficacy and safety of crizotinib based regimens on response and safety for Chinese patients with EML4-ALK positive non-small-cell lung cancer were identified by using a predefined search strategy.	Crizotinib	78-88	EMAP like 4	Homo sapiens	153-157
26107243-2	2015	MATERIALS AND METHODS: Clinical studies evaluating the efficacy and safety of crizotinib based regimens on response and safety for Chinese patients with EML4-ALK positive non-small-cell lung cancer were identified by using a predefined search strategy.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	158-161
26107243-8	2015	CONCLUSIONS: This pooled analysis suggests that crizotinib based regimens are associated with good response rate and accepted toxicities in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer.	Crizotinib	48-58	EMAP like 4	Homo sapiens	171-175
26107243-8	2015	CONCLUSIONS: This pooled analysis suggests that crizotinib based regimens are associated with good response rate and accepted toxicities in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer.	Crizotinib	48-58	ALK receptor tyrosine kinase	Homo sapiens	176-179
25609490-7	2015	It is in progress and promising for anti-IGF-1R in Ewing sarcomas, for crizotinib in myofibroblastic inflammatory tumors, for mTOR inhibitor in PEComas...	Crizotinib	71-81	insulin like growth factor 1 receptor	Homo sapiens	41-47
25351743-0	2015	Cabozantinib overcomes crizotinib resistance in ROS1 fusion-positive cancer.	Crizotinib	23-33	Ros1 proto-oncogene	Mus musculus	48-52
25351743-2	2015	In an ongoing phase I trial, the ALK tyrosine kinase inhibitor (TKI) crizotinib shows remarkable initial responses in patients with non-small cell lung cancer (NSCLC) harboring ROS1 fusions; however, cancers eventually develop crizotinib resistance due to acquired mutations such as G2032R in ROS1.	Crizotinib	69-79	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	177-181
25351743-2	2015	In an ongoing phase I trial, the ALK tyrosine kinase inhibitor (TKI) crizotinib shows remarkable initial responses in patients with non-small cell lung cancer (NSCLC) harboring ROS1 fusions; however, cancers eventually develop crizotinib resistance due to acquired mutations such as G2032R in ROS1.	Crizotinib	69-79	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	293-297
25351743-3	2015	Thus, understanding the crizotinib-resistance mechanisms in ROS1-rearranged NSCLC and identification of therapeutic strategies to overcome the resistance are required.	Crizotinib	24-34	Ros1 proto-oncogene	Mus musculus	60-64
25351743-8	2015	RESULTS: We identified multiple novel crizotinib-resistance mutations in the ROS1 kinase domain, including the G2032R mutation.	Crizotinib	38-48	Ros1 proto-oncogene	Mus musculus	77-81
26498130-0	2015	Patterns of response to crizotinib in recurrent glioblastoma according to ALK and MET molecular profile in two patients.	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	74-77
26498130-1	2015	Two patients with an unmethylated MGMT promoter and IDH1 (R132H) wild-type recurrent glioblastoma were treated with crizotinib.	Crizotinib	116-126	O-6-methylguanine-DNA methyltransferase	Homo sapiens	34-38
26498130-1	2015	Two patients with an unmethylated MGMT promoter and IDH1 (R132H) wild-type recurrent glioblastoma were treated with crizotinib.	Crizotinib	116-126	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	52-56
26264346-2	2015	Crizotinib, an orally available small molecule, has been the first ALK inhibitor to demonstrate a significant clinical activity in patients with ALK-positive tumors and, thus, to achieve the US food and drug administration approval for the treatment of advanced NSCLC harboring ALK-rearrangements.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	67-70
26264346-2	2015	Crizotinib, an orally available small molecule, has been the first ALK inhibitor to demonstrate a significant clinical activity in patients with ALK-positive tumors and, thus, to achieve the US food and drug administration approval for the treatment of advanced NSCLC harboring ALK-rearrangements.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	145-148
26264346-2	2015	Crizotinib, an orally available small molecule, has been the first ALK inhibitor to demonstrate a significant clinical activity in patients with ALK-positive tumors and, thus, to achieve the US food and drug administration approval for the treatment of advanced NSCLC harboring ALK-rearrangements.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	145-148
26264346-4	2015	Three main mechanisms of resistance to crizotinib have been identified to date: mutations in the ALK kinase domain, amplifications of ALK gene, and activation of escape signaling pathways.	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	97-100
26264346-4	2015	Three main mechanisms of resistance to crizotinib have been identified to date: mutations in the ALK kinase domain, amplifications of ALK gene, and activation of escape signaling pathways.	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	134-137
26264346-5	2015	As ALK signaling dependence is retained in most cases become refractory to crizotinib, newer and more potent ALK-inhibitors have been developed and tested in clinical trials with encouraging activity results.	Crizotinib	75-85	ALK receptor tyrosine kinase	Homo sapiens	109-112
25757678-2	2015	Crizotinib is a small-molecule oral inhibitor of ALK, c-Met/HGF receptor and ROS1 receptor kinases.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	54-59
25757678-2	2015	Crizotinib is a small-molecule oral inhibitor of ALK, c-Met/HGF receptor and ROS1 receptor kinases.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	60-72
25757678-2	2015	Crizotinib is a small-molecule oral inhibitor of ALK, c-Met/HGF receptor and ROS1 receptor kinases.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	77-81
25757678-4	2015	Crizotinib"s effect on ROS1 receptor kinases and c-Met with relevance to NSCLC is also actively being explored.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	23-27
25757678-4	2015	Crizotinib"s effect on ROS1 receptor kinases and c-Met with relevance to NSCLC is also actively being explored.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	49-54
25757678-5	2015	Resistance mechanisms such as secondary gatekeeper mutations in ALK gene and activation of other oncogenes have been identified to confer acquired resistance to crizotinib.	Crizotinib	161-171	ALK receptor tyrosine kinase	Homo sapiens	64-67
25757678-6	2015	This article reviews the pharmacological properties of crizotinib, preclinical and clinical results that led to its approval in ALK-positive NSCLC and current directions of clinical research in overcoming crizotinib resistance.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	128-131
26666609-0	2015	Alternate-day Treatment with Crizotinib for Drug-induced Esophagitis and Liver Damage in a Patient with EML4-ALK Fusion Gene-positive Lung Adenocarcinoma.	Crizotinib	29-39	EMAP like 4	Homo sapiens	104-108
26568007-1	2015	A 55-year-old woman was diagnosed with a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) rearrangement-positive lung adenocarcinoma and treated with chemotherapy consisting of crizotinib, a tyrosine kinase inhibitor of ALK, as second-line chemotherapy.	Crizotinib	190-200	ALK receptor tyrosine kinase	Homo sapiens	70-96
26666609-0	2015	Alternate-day Treatment with Crizotinib for Drug-induced Esophagitis and Liver Damage in a Patient with EML4-ALK Fusion Gene-positive Lung Adenocarcinoma.	Crizotinib	29-39	ALK receptor tyrosine kinase	Homo sapiens	109-112
26568007-1	2015	A 55-year-old woman was diagnosed with a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) rearrangement-positive lung adenocarcinoma and treated with chemotherapy consisting of crizotinib, a tyrosine kinase inhibitor of ALK, as second-line chemotherapy.	Crizotinib	190-200	ALK receptor tyrosine kinase	Homo sapiens	233-236
25381264-6	2015	Treatment with single-agent crizotinib reduced tumor vascularization but failed to inhibit tumor growth in either model, despite also a significant increase of c-met expression and phosphorylation in the sunitinib-resistant tumors.	Crizotinib	28-38	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	160-165
25230898-0	2015	Response to crizotinib observed in metastatic mediastinum lymph node from a non-small cell lung cancer patient harboring EZR-ROS1 fusion.	Crizotinib	12-22	ezrin	Homo sapiens	121-124
25230898-0	2015	Response to crizotinib observed in metastatic mediastinum lymph node from a non-small cell lung cancer patient harboring EZR-ROS1 fusion.	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	125-129
24990113-1	2015	Crizotinib (Xalkori ) is an orally administered, selective, small-molecule, ATP-competitive inhibitor of the anaplastic lymphoma kinase (ALK) and mesenchymal epithelial transition factor/hepatocyte growth factor receptor tyrosine kinases, and has recently been approved for the treatment of ALK-positive non-small cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	109-135
24990113-1	2015	Crizotinib (Xalkori ) is an orally administered, selective, small-molecule, ATP-competitive inhibitor of the anaplastic lymphoma kinase (ALK) and mesenchymal epithelial transition factor/hepatocyte growth factor receptor tyrosine kinases, and has recently been approved for the treatment of ALK-positive non-small cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	137-140
24990113-1	2015	Crizotinib (Xalkori ) is an orally administered, selective, small-molecule, ATP-competitive inhibitor of the anaplastic lymphoma kinase (ALK) and mesenchymal epithelial transition factor/hepatocyte growth factor receptor tyrosine kinases, and has recently been approved for the treatment of ALK-positive non-small cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	291-294
25971657-6	2015	Specific inhibitors of the kinase activity of ALK have been developed as therapeutic drugs for EML4-ALK-positive lung cancer, three of which (crizotinib, ceritinib, and alectinib) have already been approved for clinical use.	Crizotinib	142-152	ALK receptor tyrosine kinase	Homo sapiens	46-49
25990337-5	2015	Patients with ALK rearrangements treated with specific ALK inhibitors such as crizotinib or EGFR-activating mutations treated with gefitinib, erlotinib or afatinib have improved progression-free survival and better quality of life than patients treated with chemotherapy.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	14-17
25990337-5	2015	Patients with ALK rearrangements treated with specific ALK inhibitors such as crizotinib or EGFR-activating mutations treated with gefitinib, erlotinib or afatinib have improved progression-free survival and better quality of life than patients treated with chemotherapy.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	55-58
26045026-2	2015	The PROFILE trials demonstrated that patients with ALK-rearranged NSCLC can be successfully treated with crizotinib, and that crizotinib is superior to chemotherapy in both first- and second-line settings.	Crizotinib	105-115	ALK receptor tyrosine kinase	Homo sapiens	51-54
25971657-6	2015	Specific inhibitors of the kinase activity of ALK have been developed as therapeutic drugs for EML4-ALK-positive lung cancer, three of which (crizotinib, ceritinib, and alectinib) have already been approved for clinical use.	Crizotinib	142-152	EMAP like 4	Homo sapiens	95-99
26273329-5	2015	For patients with anaplastic lymphoma kinase (ALK) gene rearrangement, Crizotinib is a promising treatment in advanced NSCLC patients.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	18-44
26273329-5	2015	For patients with anaplastic lymphoma kinase (ALK) gene rearrangement, Crizotinib is a promising treatment in advanced NSCLC patients.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	46-49
25326243-1	2015	Crizotinib (Xalkori) is a tyrosine kinase inhibitor of both anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition factor (c-Met).	Crizotinib	0-10	ALK receptor tyrosine kinase	Rattus norvegicus	60-86
25326243-1	2015	Crizotinib (Xalkori) is a tyrosine kinase inhibitor of both anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition factor (c-Met).	Crizotinib	0-10	ALK receptor tyrosine kinase	Rattus norvegicus	88-91
25326243-1	2015	Crizotinib (Xalkori) is a tyrosine kinase inhibitor of both anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition factor (c-Met).	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	139-144
25326243-10	2015	Collectively, our results suggest that the ERG b-wave amplitude decreases during dark adaption following crizotinib administration may be related to signaling changes within the retina in rats, likely independent of ALK inhibition.	Crizotinib	105-115	ALK receptor tyrosine kinase	Rattus norvegicus	216-219
25034009-2	2015	Crizotinib (XALKORI ), an oral inhibitor of anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition factor kinase (c-Met), is currently approved for the treatment of patients with non-small cell lung cancer that is ALK-positive.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	44-70
25428710-8	2015	In preclinical models, alectinib was active against most ALK fusion-gene mutations related to crizotinib resistance, and preliminary results from clinical trials indicate efficacy in crizotinib-refractory NSCLC.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	57-60
25527865-10	2014	The response of SqCC patients with ALK expression to target therapy of crizotinib should be explored.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	35-38
25034009-2	2015	Crizotinib (XALKORI ), an oral inhibitor of anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition factor kinase (c-Met), is currently approved for the treatment of patients with non-small cell lung cancer that is ALK-positive.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	13-16
25034009-2	2015	Crizotinib (XALKORI ), an oral inhibitor of anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition factor kinase (c-Met), is currently approved for the treatment of patients with non-small cell lung cancer that is ALK-positive.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	130-135
25034009-2	2015	Crizotinib (XALKORI ), an oral inhibitor of anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition factor kinase (c-Met), is currently approved for the treatment of patients with non-small cell lung cancer that is ALK-positive.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	72-75
25548525-11	2015	In anaplastic lymphoma kinase-positive nonsquamous advanced NSCLC, the ICER of first-line crizotinib compared with that of chemotherapy was $255,970 per QALY.	Crizotinib	90-100	cAMP responsive element modulator	Homo sapiens	71-75
25470694-1	2014	BACKGROUND: The efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC) is unknown.	Crizotinib	46-56	ALK receptor tyrosine kinase	Homo sapiens	32-35
25501361-0	2014	Efficacy and safety of crizotinib among Chinese EML4-ALK-positive, advanced-stage non-small cell lung cancer patients.	Crizotinib	23-33	EMAP like 4	Homo sapiens	48-52
25501361-0	2014	Efficacy and safety of crizotinib among Chinese EML4-ALK-positive, advanced-stage non-small cell lung cancer patients.	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	53-56
25501361-2	2014	METHODS: We retrospectively analyzed patients with EML4-ALK positive advanced NSCLC who were treated with crizotinib from May 2012 to Aug 2013.	Crizotinib	106-116	EMAP like 4	Homo sapiens	51-55
25501361-2	2014	METHODS: We retrospectively analyzed patients with EML4-ALK positive advanced NSCLC who were treated with crizotinib from May 2012 to Aug 2013.	Crizotinib	106-116	ALK receptor tyrosine kinase	Homo sapiens	56-59
25501361-16	2014	CONCLUSIONS: Crizotinib was safe, well-tolerated, and effective in Chinese patients with pre-treated ALK-rearranged NSCLC.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	101-104
25470694-11	2014	CONCLUSIONS: Crizotinib was superior to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	145-148
25266653-7	2014	C-MET inhibitors can be classified into three groups: small-molecule tyrosine kinase inhibitors of the c-MET receptor (crizotinib, tivantinib, cabozantinib, foretinib), as well as monoclonal antibodies against c-MET (onartuzumab) and against the HGF ligand (ficlatuzumab, rilotumumab).	Crizotinib	119-129	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	0-5
24766435-9	2014	The anti-CD30 immunoconjugate Brentuximab Vedotin and the specific ALK inhibitor Crizotinib are changing the treatment paradigm in ALCL (ALK-positive or negative) and ALK-positive ALCL respectively.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	67-70
24766435-9	2014	The anti-CD30 immunoconjugate Brentuximab Vedotin and the specific ALK inhibitor Crizotinib are changing the treatment paradigm in ALCL (ALK-positive or negative) and ALK-positive ALCL respectively.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	137-140
24766435-9	2014	The anti-CD30 immunoconjugate Brentuximab Vedotin and the specific ALK inhibitor Crizotinib are changing the treatment paradigm in ALCL (ALK-positive or negative) and ALK-positive ALCL respectively.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	137-140
25301075-4	2014	EXPERT OPINION: Available data demonstrated that crizotinib is the best option we can offer today to ALK-positive NSCLC not previously exposed to ALK inhibitors, irrespective of line of therapy.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	101-104
25381900-9	2014	Crizotinib is superior to chemotherapy in the first-line setting for ALK-positive NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	69-72
25401476-8	2014	ROS1 inhibition with crizotinib and deglutathiolation of SHP-2 abolished GPX1-mediated increases in VSMC proliferation while leaving endothelialization intact.	Crizotinib	21-31	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	0-4
25247338-3	2014	The incredible story of ALK rearranged tumors, with the rapid Food and Drug Administration approval of Crizotinib after only 4 years from the discovery of EML4-ALK translocation in NSCLC, has profoundly influenced the concept of drug development in NSCLC, paving the way to a novel series of molecularly selected studies with specific inhibitors.	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	24-27
25247338-3	2014	The incredible story of ALK rearranged tumors, with the rapid Food and Drug Administration approval of Crizotinib after only 4 years from the discovery of EML4-ALK translocation in NSCLC, has profoundly influenced the concept of drug development in NSCLC, paving the way to a novel series of molecularly selected studies with specific inhibitors.	Crizotinib	103-113	EMAP like 4	Homo sapiens	155-159
25247338-3	2014	The incredible story of ALK rearranged tumors, with the rapid Food and Drug Administration approval of Crizotinib after only 4 years from the discovery of EML4-ALK translocation in NSCLC, has profoundly influenced the concept of drug development in NSCLC, paving the way to a novel series of molecularly selected studies with specific inhibitors.	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	160-163
25393798-0	2014	Secondary mutations at I1171 in the ALK gene confer resistance to both Crizotinib and Alectinib.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	36-39
25364439-0	2014	Responses to crizotinib in a patient with c-ros oncogene 1, receptor tyrosine kinase-positive advanced lung adenocarcinoma: A case report.	Crizotinib	13-23	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	42-84
25364439-3	2014	ROS1 rearrangements can be detected using fluorescence in situ hybridization (FISH), which is considered the gold standard technique in detecting ROS1 rearrangements, and determining whether a patient would respond well to crizotinib treatment.	Crizotinib	223-233	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	0-4
25301075-4	2014	EXPERT OPINION: Available data demonstrated that crizotinib is the best option we can offer today to ALK-positive NSCLC not previously exposed to ALK inhibitors, irrespective of line of therapy.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	146-149
25539610-2	2014	The first-in-class ALK tyrosine kinase inhibitor, crizotinib, can effectively target these tumors represent a significant advance in the evolution of personalized medicine for NSCLC.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	19-22
25539610-3	2014	A randomized phase III clinical trial in which superiority of crizotinib over chemotherapy was seen in previously treated ALK-positive NSCLC patients demonstrated durable responses and well tolerance in the majority of ALK-positive NSCLC patients treated with crizotinib.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	122-125
25539610-3	2014	A randomized phase III clinical trial in which superiority of crizotinib over chemotherapy was seen in previously treated ALK-positive NSCLC patients demonstrated durable responses and well tolerance in the majority of ALK-positive NSCLC patients treated with crizotinib.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	219-222
25539610-3	2014	A randomized phase III clinical trial in which superiority of crizotinib over chemotherapy was seen in previously treated ALK-positive NSCLC patients demonstrated durable responses and well tolerance in the majority of ALK-positive NSCLC patients treated with crizotinib.	Crizotinib	260-270	ALK receptor tyrosine kinase	Homo sapiens	219-222
25450694-1	2014	Neuroblastoma (NB) patients harboring mutated ALK can be expected to potentially benefit from targeted therapy based on ALK tyrosine kinase inhibitor (TKI), such as crizotinib and ceritinib.	Crizotinib	165-175	ALK receptor tyrosine kinase	Homo sapiens	46-49
25450694-1	2014	Neuroblastoma (NB) patients harboring mutated ALK can be expected to potentially benefit from targeted therapy based on ALK tyrosine kinase inhibitor (TKI), such as crizotinib and ceritinib.	Crizotinib	165-175	ALK receptor tyrosine kinase	Homo sapiens	120-123
25450694-6	2014	Ligand-dependent Axl activation obviously rescued crizotinib-mediated suppression of cell proliferation in ALK-mutated NB cells.	Crizotinib	50-60	AXL receptor tyrosine kinase	Homo sapiens	17-20
25450694-6	2014	Ligand-dependent Axl activation obviously rescued crizotinib-mediated suppression of cell proliferation in ALK-mutated NB cells.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	107-110
25264305-0	2014	Crizotinib in ROS1-rearranged non-small-cell lung cancer.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	14-18
25264305-2	2014	Crizotinib is a small-molecule tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and another proto-oncogene receptor tyrosine kinase, MET.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	60-86
25264305-2	2014	Crizotinib is a small-molecule tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and another proto-oncogene receptor tyrosine kinase, MET.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	88-91
25264305-2	2014	Crizotinib is a small-molecule tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and another proto-oncogene receptor tyrosine kinase, MET.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	94-98
25264305-12	2014	CONCLUSIONS: In this study, crizotinib showed marked antitumor activity in patients with advanced ROS1-rearranged NSCLC.	Crizotinib	28-38	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	98-102
25264305-13	2014	ROS1 rearrangement defines a second molecular subgroup of NSCLC for which crizotinib is highly active.	Crizotinib	74-84	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	0-4
25429239-3	2014	ALK+ NSCLC cells respond well to small molecule ALK inhibitors such as crizotinib; however, resistance invariably develops after several months of treatment.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	0-3
25429239-3	2014	ALK+ NSCLC cells respond well to small molecule ALK inhibitors such as crizotinib; however, resistance invariably develops after several months of treatment.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	48-51
25407901-3	2014	In contrast, ALK tyrosine kinase inhibitor (ALK TKI) crizotinib has shown superior effects in combating NSCLCs with EML4-ALK.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	13-16
25407901-3	2014	In contrast, ALK tyrosine kinase inhibitor (ALK TKI) crizotinib has shown superior effects in combating NSCLCs with EML4-ALK.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	44-47
25407901-3	2014	In contrast, ALK tyrosine kinase inhibitor (ALK TKI) crizotinib has shown superior effects in combating NSCLCs with EML4-ALK.	Crizotinib	53-63	EMAP like 4	Homo sapiens	116-120
25407901-3	2014	In contrast, ALK tyrosine kinase inhibitor (ALK TKI) crizotinib has shown superior effects in combating NSCLCs with EML4-ALK.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	44-47
25228534-1	2014	PURPOSE: The first-generation ALK tyrosine kinase inhibitor (TKI) crizotinib is a standard therapy for patients with ALK-rearranged non-small cell lung cancer (NSCLC).	Crizotinib	66-76	ALK receptor tyrosine kinase	Homo sapiens	30-33
25266653-10	2014	The best understood c-MET inhibitor used in the treatment of non-small-cell lung carcinoma patients is crizotinib.	Crizotinib	103-113	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	20-25
25228534-1	2014	PURPOSE: The first-generation ALK tyrosine kinase inhibitor (TKI) crizotinib is a standard therapy for patients with ALK-rearranged non-small cell lung cancer (NSCLC).	Crizotinib	66-76	ALK receptor tyrosine kinase	Homo sapiens	117-120
25228534-2	2014	Several next-generation ALK-TKIs have entered the clinic and have shown promising activity in crizotinib-resistant patients.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	24-27
25228534-9	2014	Both ALK mutations conferred resistance to alectinib as well as to crizotinib, but were sensitive to ceritinib and other next-generation ALK-TKIs.	Crizotinib	67-77	ALK receptor tyrosine kinase	Homo sapiens	5-8
24885803-0	2014	ALK rearrangement in a large series of consecutive non-small cell lung cancers: comparison between a new immunohistochemical approach and fluorescence in situ hybridization for the screening of patients eligible for crizotinib treatment.	Crizotinib	216-226	ALK receptor tyrosine kinase	Homo sapiens	0-3
25205428-1	2014	PURPOSE: The clinical efficacy of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been demonstrated in ALK fusion-positive non-small cell lung cancer (NSCLC); however, brain metastases are frequent sites of initial failure in patients due to poor penetration of the central nervous system by crizotinib.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	38-64
25205428-1	2014	PURPOSE: The clinical efficacy of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been demonstrated in ALK fusion-positive non-small cell lung cancer (NSCLC); however, brain metastases are frequent sites of initial failure in patients due to poor penetration of the central nervous system by crizotinib.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	66-69
25205428-1	2014	PURPOSE: The clinical efficacy of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been demonstrated in ALK fusion-positive non-small cell lung cancer (NSCLC); however, brain metastases are frequent sites of initial failure in patients due to poor penetration of the central nervous system by crizotinib.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	117-120
25205428-1	2014	PURPOSE: The clinical efficacy of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been demonstrated in ALK fusion-positive non-small cell lung cancer (NSCLC); however, brain metastases are frequent sites of initial failure in patients due to poor penetration of the central nervous system by crizotinib.	Crizotinib	306-316	ALK receptor tyrosine kinase	Homo sapiens	38-64
25205428-1	2014	PURPOSE: The clinical efficacy of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been demonstrated in ALK fusion-positive non-small cell lung cancer (NSCLC); however, brain metastases are frequent sites of initial failure in patients due to poor penetration of the central nervous system by crizotinib.	Crizotinib	306-316	ALK receptor tyrosine kinase	Homo sapiens	66-69
25087901-0	2014	Dramatic response to crizotinib in ROS1 fluorescent in situ hybridization- and immunohistochemistry-positive lung adenocarcinoma: a case series.	Crizotinib	21-31	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	35-39
25436807-1	2014	The tyrosine kinase inhibitor crizotinib is an effective therapy for patients with cancers harboring rearrangements of the anaplastic lymphoma kinase (ALK) gene.	Crizotinib	30-40	ALK receptor tyrosine kinase	Homo sapiens	123-149
25436807-1	2014	The tyrosine kinase inhibitor crizotinib is an effective therapy for patients with cancers harboring rearrangements of the anaplastic lymphoma kinase (ALK) gene.	Crizotinib	30-40	ALK receptor tyrosine kinase	Homo sapiens	151-154
25436807-2	2014	Here, we describe two patients with advanced ALK-positive lung cancer who developed hypersensitivity to crizotinib, requiring temporary discontinuation of the drug.	Crizotinib	104-114	ALK receptor tyrosine kinase	Homo sapiens	45-48
25453376-3	2014	Crizotinib, which is a first-in-class ALK tyrosine kinase inhibitor (TKI), was shown to be effective and well tolerated in ALK-positive NSCLC patients by a single-arm phase I study.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	38-41
25453376-3	2014	Crizotinib, which is a first-in-class ALK tyrosine kinase inhibitor (TKI), was shown to be effective and well tolerated in ALK-positive NSCLC patients by a single-arm phase I study.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	123-126
25453376-4	2014	Furthermore, a phase III randomized study demonstrated the superiority of crizotinib to standard chemotherapy (pemetrexed or docetaxel) in the treatment of NSCLC patients harboring the ALK rearrangement who had received one prior platinum-based chemotherapy.	Crizotinib	74-84	ALK receptor tyrosine kinase	Homo sapiens	185-188
25453376-5	2014	However, the mechanisms of resistance to crizotinib are major concerns when administering crizotinib to ALK-positive NSCLC patients, and they include second mutations and a gain in the copy number of the ALK gene, activation of other oncogenes, etc.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	104-107
25453376-5	2014	However, the mechanisms of resistance to crizotinib are major concerns when administering crizotinib to ALK-positive NSCLC patients, and they include second mutations and a gain in the copy number of the ALK gene, activation of other oncogenes, etc.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	204-207
25453376-5	2014	However, the mechanisms of resistance to crizotinib are major concerns when administering crizotinib to ALK-positive NSCLC patients, and they include second mutations and a gain in the copy number of the ALK gene, activation of other oncogenes, etc.	Crizotinib	90-100	ALK receptor tyrosine kinase	Homo sapiens	104-107
27202548-0	2014	Budget Impact Analysis Of Crizotinib Treatment In Alk+ Non-Small-Cell Lung Cancer Patients In Thailand.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	50-53
27202302-0	2014	The Cost-Effectiveness of Second-Line Crizotinib in Eml4-Alk Rearranged Advanced Non-Small Cell Lung Cancer.	Crizotinib	38-48	EMAP like 4	Homo sapiens	52-56
27202302-0	2014	The Cost-Effectiveness of Second-Line Crizotinib in Eml4-Alk Rearranged Advanced Non-Small Cell Lung Cancer.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	57-60
25489176-2	2014	This led to successful evidence of using tyrosine kinase inhibitors (TKIs) over the standard platinum doublet based chemotherapy as the first line treatment in the metastatic setting.The rearrangements of fusion protein EML4-ALK in NSCLC lead to the use of crizotinib for this class of tumors.	Crizotinib	257-267	EMAP like 4	Homo sapiens	220-224
25489176-2	2014	This led to successful evidence of using tyrosine kinase inhibitors (TKIs) over the standard platinum doublet based chemotherapy as the first line treatment in the metastatic setting.The rearrangements of fusion protein EML4-ALK in NSCLC lead to the use of crizotinib for this class of tumors.	Crizotinib	257-267	ALK receptor tyrosine kinase	Homo sapiens	225-228
25489176-4	2014	Although robust responses to crizotinib are observed in NSCLC harboring ALK mutations, majority of tumors eventually become resistant, posing a major challenge in treatment course.	Crizotinib	29-39	ALK receptor tyrosine kinase	Homo sapiens	72-75
25351246-2	2014	The clinical efficacy of the ALK inhibitor, crizotinib, lags behind expectations for treating MYCN-amplified, ALK-mutant neuroblastoma, a deadly childhood cancer.	Crizotinib	44-54	ALK receptor tyrosine kinase	Homo sapiens	29-32
25351247-6	2014	Pharmacological or RNA interference-mediated inhibition of ERK5 suppressed the proliferation of neuroblastoma cells in culture and enhanced the antitumor efficacy of the ALK inhibitor crizotinib in both cells and xenograft models.	Crizotinib	184-194	mitogen-activated protein kinase 7	Homo sapiens	59-63
25351247-6	2014	Pharmacological or RNA interference-mediated inhibition of ERK5 suppressed the proliferation of neuroblastoma cells in culture and enhanced the antitumor efficacy of the ALK inhibitor crizotinib in both cells and xenograft models.	Crizotinib	184-194	ALK receptor tyrosine kinase	Homo sapiens	170-173
25193856-0	2014	Crizotinib exhibits antitumor activity by targeting ALK signaling not c-MET in pancreatic cancer.	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	52-55
25193856-1	2014	Crizotinib, a c-MET/ALK inhibitor, has exhibited antitumor efficacy in different types of cancers.	Crizotinib	0-10	met proto-oncogene	Mus musculus	14-19
25193856-1	2014	Crizotinib, a c-MET/ALK inhibitor, has exhibited antitumor efficacy in different types of cancers.	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	20-23
25193856-6	2014	In the study, with regard to the mechanism of action, Crizotinib did not inhibit c-MET expression on pancreatic cancer cells; instead, it specifically inhibited the activity of ALK, which was identified to be highly expressed on various pancreatic cancer cells and tissues in our study.	Crizotinib	54-64	anaplastic lymphoma kinase	Mus musculus	177-180
25193856-7	2014	In 42 different receptor tyrosine kinase (RTKs) array, Crizotinib also strongly inhibited the expression of activated ALK in pancreatic cancer cells, modulating its downstream mediators such as STAT3, AKT, and ERK.	Crizotinib	55-65	TYRO3 protein tyrosine kinase 3	Mus musculus	16-40
25193856-7	2014	In 42 different receptor tyrosine kinase (RTKs) array, Crizotinib also strongly inhibited the expression of activated ALK in pancreatic cancer cells, modulating its downstream mediators such as STAT3, AKT, and ERK.	Crizotinib	55-65	TYRO3 protein tyrosine kinase 3	Mus musculus	42-46
25193856-7	2014	In 42 different receptor tyrosine kinase (RTKs) array, Crizotinib also strongly inhibited the expression of activated ALK in pancreatic cancer cells, modulating its downstream mediators such as STAT3, AKT, and ERK.	Crizotinib	55-65	anaplastic lymphoma kinase	Mus musculus	118-121
25193856-7	2014	In 42 different receptor tyrosine kinase (RTKs) array, Crizotinib also strongly inhibited the expression of activated ALK in pancreatic cancer cells, modulating its downstream mediators such as STAT3, AKT, and ERK.	Crizotinib	55-65	signal transducer and activator of transcription 3	Mus musculus	194-199
25193856-7	2014	In 42 different receptor tyrosine kinase (RTKs) array, Crizotinib also strongly inhibited the expression of activated ALK in pancreatic cancer cells, modulating its downstream mediators such as STAT3, AKT, and ERK.	Crizotinib	55-65	thymoma viral proto-oncogene 1	Mus musculus	201-204
25193856-7	2014	In 42 different receptor tyrosine kinase (RTKs) array, Crizotinib also strongly inhibited the expression of activated ALK in pancreatic cancer cells, modulating its downstream mediators such as STAT3, AKT, and ERK.	Crizotinib	55-65	Eph receptor B2	Mus musculus	210-213
25193856-9	2014	Taken together, our investigation shows that Crizotinib inhibits the ALK signaling pathway in pancreatic cancer, resulting in cell growth/angiogenesis inhibition and apoptosis induction.	Crizotinib	45-55	anaplastic lymphoma kinase	Mus musculus	69-72
25277255-4	2014	In this study we tested multi-kinase inhibitors: axitinib (VEGFR inhibitor) and crizotinib (c-MET inhibitor) in a combination trial in mice models.	Crizotinib	80-90	met proto-oncogene	Mus musculus	92-97
25275109-3	2014	The apoptosis inducer crizotinib is a small-molecule inhibitor of c-Met, a receptor tyrosine kinase that is often dysregulated in human tumors.	Crizotinib	22-32	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	66-71
24856155-2	2014	Patients with ALK-rearranged NSCLC are initially sensitive to the ALK inhibitor crizotinib but eventually become resistant, limiting its therapeutic potential.	Crizotinib	80-90	ALK receptor tyrosine kinase	Homo sapiens	14-17
24856155-2	2014	Patients with ALK-rearranged NSCLC are initially sensitive to the ALK inhibitor crizotinib but eventually become resistant, limiting its therapeutic potential.	Crizotinib	80-90	ALK receptor tyrosine kinase	Homo sapiens	66-69
25170635-1	2014	BACKGROUND: The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has recently received approval for the treatment of patients with locally advanced or metastatic ALK-positive non-small-cell lung cancer (NSCLC).	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	16-42
25170635-1	2014	BACKGROUND: The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has recently received approval for the treatment of patients with locally advanced or metastatic ALK-positive non-small-cell lung cancer (NSCLC).	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	44-47
25170635-1	2014	BACKGROUND: The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has recently received approval for the treatment of patients with locally advanced or metastatic ALK-positive non-small-cell lung cancer (NSCLC).	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	167-170
25228590-6	2014	Combined treatment with crizotinib and an ATP-competitive mTOR inhibitor abrogated RPS6 phosphorylation, leading to reduced tumor growth and prolonged survival in ALK(F1174L)/MYCN-positive models compared to single agent treatment.	Crizotinib	24-34	ribosomal protein S6	Homo sapiens	83-87
25228590-6	2014	Combined treatment with crizotinib and an ATP-competitive mTOR inhibitor abrogated RPS6 phosphorylation, leading to reduced tumor growth and prolonged survival in ALK(F1174L)/MYCN-positive models compared to single agent treatment.	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	163-166
25806325-3	2014	Moreover the first ALK inhibitor, crizotinib (Xalkori or PF02341066) was successfully approved for the treatment of late stages or metastatic ALK+ NSCLC, giving a new, safer therapeutic option for those patients.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	19-22
25806325-3	2014	Moreover the first ALK inhibitor, crizotinib (Xalkori or PF02341066) was successfully approved for the treatment of late stages or metastatic ALK+ NSCLC, giving a new, safer therapeutic option for those patients.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	142-145
25035277-0	2014	Clinical benefit of continuing ALK inhibition with crizotinib beyond initial disease progression in patients with advanced ALK-positive NSCLC.	Crizotinib	51-61	ALK receptor tyrosine kinase	Homo sapiens	31-34
25035278-0	2014	Reply to the letter to the editor "clinical benefit of continuing ALK inhibition with crizotinib beyond initial disease progression in patients with advanced ALK-positive NSCLC" by Ou et al.	Crizotinib	86-96	ALK receptor tyrosine kinase	Homo sapiens	66-69
25035278-0	2014	Reply to the letter to the editor "clinical benefit of continuing ALK inhibition with crizotinib beyond initial disease progression in patients with advanced ALK-positive NSCLC" by Ou et al.	Crizotinib	86-96	ALK receptor tyrosine kinase	Homo sapiens	158-161
25096400-1	2014	Patients with non-small cell lung cancer (NSCLC) with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements generally respond to ALK inhibitors such as crizotinib.	Crizotinib	202-212	EMAP like 4	Homo sapiens	54-102
25096400-1	2014	Patients with non-small cell lung cancer (NSCLC) with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements generally respond to ALK inhibitors such as crizotinib.	Crizotinib	202-212	EMAP like 4	Homo sapiens	104-108
25096400-1	2014	Patients with non-small cell lung cancer (NSCLC) with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements generally respond to ALK inhibitors such as crizotinib.	Crizotinib	202-212	ALK receptor tyrosine kinase	Homo sapiens	138-141
25096400-1	2014	Patients with non-small cell lung cancer (NSCLC) with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements generally respond to ALK inhibitors such as crizotinib.	Crizotinib	202-212	ALK receptor tyrosine kinase	Homo sapiens	179-182
25096400-2	2014	However, some patients with EML4-ALK rearrangements respond poorly to crizotinib.	Crizotinib	70-80	EMAP like 4	Homo sapiens	28-32
25096400-2	2014	However, some patients with EML4-ALK rearrangements respond poorly to crizotinib.	Crizotinib	70-80	ALK receptor tyrosine kinase	Homo sapiens	33-36
25170107-7	2014	Because the EML4-ALK rearrangement was found in a biopsied specimen using fluorescence in situ hybridization, she was treated with crizotinib.	Crizotinib	131-141	EMAP like 4	Homo sapiens	12-16
25170107-7	2014	Because the EML4-ALK rearrangement was found in a biopsied specimen using fluorescence in situ hybridization, she was treated with crizotinib.	Crizotinib	131-141	ALK receptor tyrosine kinase	Homo sapiens	17-20
25170107-14	2014	Phosphorylated ALK protein and its downstream signaling were suppressed by treatment with crizotinib in western blotting.	Crizotinib	90-100	ALK receptor tyrosine kinase	Homo sapiens	15-18
25170012-1	2014	On August 26, 2011, crizotinib received accelerated approval for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is ALK-positive as detected by a test approved by the U.S. Food and Drug Administration (FDA).	Crizotinib	20-30	ALK receptor tyrosine kinase	Homo sapiens	170-173
25170012-3	2014	On November 20, 2013, crizotinib received regular approval based on confirmation of clinical benefit in study A8081007, a randomized trial in 347 patients with ALK-positive advanced NSCLC who had previously received one platinum-containing regimen.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	160-163
25170012-9	2014	Crizotinib"s rapid clinical development program (6 years from identification of ALK rearrangements in a subset of NSCLC to full FDA approval) is a model of efficient drug development in this new era of molecularly targeted oncology therapy.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	80-83
25228590-2	2014	The ALK(F1174L) mutation is sensitive to the ALK inhibitor crizotinib only at high doses and mediates acquired resistance to crizotinib in ALK-translocated cancers.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	4-7
25228590-2	2014	The ALK(F1174L) mutation is sensitive to the ALK inhibitor crizotinib only at high doses and mediates acquired resistance to crizotinib in ALK-translocated cancers.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	45-48
25228590-2	2014	The ALK(F1174L) mutation is sensitive to the ALK inhibitor crizotinib only at high doses and mediates acquired resistance to crizotinib in ALK-translocated cancers.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	45-48
25228590-2	2014	The ALK(F1174L) mutation is sensitive to the ALK inhibitor crizotinib only at high doses and mediates acquired resistance to crizotinib in ALK-translocated cancers.	Crizotinib	125-135	ALK receptor tyrosine kinase	Homo sapiens	4-7
25228590-2	2014	The ALK(F1174L) mutation is sensitive to the ALK inhibitor crizotinib only at high doses and mediates acquired resistance to crizotinib in ALK-translocated cancers.	Crizotinib	125-135	ALK receptor tyrosine kinase	Homo sapiens	45-48
25228590-2	2014	The ALK(F1174L) mutation is sensitive to the ALK inhibitor crizotinib only at high doses and mediates acquired resistance to crizotinib in ALK-translocated cancers.	Crizotinib	125-135	ALK receptor tyrosine kinase	Homo sapiens	45-48
25228590-3	2014	We have shown that the combination of crizotinib and an inhibitor of downstream signaling induces a favorable response in transgenic mice bearing ALK(F1174L)/MYCN-positive neuroblastoma.	Crizotinib	38-48	anaplastic lymphoma kinase	Mus musculus	146-149
25228590-3	2014	We have shown that the combination of crizotinib and an inhibitor of downstream signaling induces a favorable response in transgenic mice bearing ALK(F1174L)/MYCN-positive neuroblastoma.	Crizotinib	38-48	v-myc avian myelocytomatosis viral related oncogene, neuroblastoma derived	Mus musculus	158-162
25228590-5	2014	We show that in ALK-mutated, MYCN-amplified neuroblastoma cells, crizotinib alone does not affect mTORC1 activity as indicated by persistent RPS6 phosphorylation.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	16-19
25408663-0	2014	Successful crizotinib rechallenge after crizotinib-induced organizing pneumonia in anaplastic lymphoma kinase-rearranged non-small cell lung cancer.	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	83-109
25408663-0	2014	Successful crizotinib rechallenge after crizotinib-induced organizing pneumonia in anaplastic lymphoma kinase-rearranged non-small cell lung cancer.	Crizotinib	40-50	ALK receptor tyrosine kinase	Homo sapiens	83-109
25408663-1	2014	Crizotinib, a first-line anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor, has shown promising results for the treatment of locally advanced and metastatic lung cancer presenting the ALK rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	25-51
25408663-1	2014	Crizotinib, a first-line anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor, has shown promising results for the treatment of locally advanced and metastatic lung cancer presenting the ALK rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	53-56
25408663-1	2014	Crizotinib, a first-line anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor, has shown promising results for the treatment of locally advanced and metastatic lung cancer presenting the ALK rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	193-196
25408663-4	2014	We report a 60-year-old male with ALK-rearranged non-small cell lung cancer who developed crizotinib-induced OP and was successfully rechallenged with crizotinib.	Crizotinib	90-100	ALK receptor tyrosine kinase	Homo sapiens	34-37
25408663-4	2014	We report a 60-year-old male with ALK-rearranged non-small cell lung cancer who developed crizotinib-induced OP and was successfully rechallenged with crizotinib.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	34-37
25239305-0	2014	The efficacy and safety of crizotinib in the treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer: a meta-analysis of clinical trials.	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	58-84
25239305-1	2014	BACKGROUND: Crizotinib was granted accelerated approval by the Food and Drug Administration in 2011 for the treatment of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	121-147
25239305-1	2014	BACKGROUND: Crizotinib was granted accelerated approval by the Food and Drug Administration in 2011 for the treatment of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	149-152
25239305-8	2014	The most frequently reported adverse effects of crizotinib were mild visual disturbances, nausea, vomiting, diarrhea, constipation, edema, reduction in glomerular filtration rate, and generally reversible but sometimes severe elevations in aspartate aminotransferase and alanine aminotransferase.	Crizotinib	48-58	glutamic--pyruvic transaminase	Homo sapiens	271-295
25239305-11	2014	As a novel, targeted anticancer agent, crizotinib appears to be a favorable treatment option for patients with locally advanced or metastatic ALK-positive NSCLC.	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	142-145
25207766-8	2014	Cell lines and human leukemic cells expressing ABL1, ABL2, CSF1R, and PDGFRB fusions were sensitive in vitro to dasatinib, EPOR and JAK2 rearrangements were sensitive to ruxolitinib, and the ETV6-NTRK3 fusion was sensitive to crizotinib.	Crizotinib	226-236	ABL proto-oncogene 1, non-receptor tyrosine kinase	Homo sapiens	47-51
25207766-8	2014	Cell lines and human leukemic cells expressing ABL1, ABL2, CSF1R, and PDGFRB fusions were sensitive in vitro to dasatinib, EPOR and JAK2 rearrangements were sensitive to ruxolitinib, and the ETV6-NTRK3 fusion was sensitive to crizotinib.	Crizotinib	226-236	erythropoietin receptor	Homo sapiens	123-127
25178493-0	2014	Activity of crizotinib over choroidal metastases in non-small-cell lung cancer (NSCLC)-ALK rearranged: a case report.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	87-90
25178493-1	2014	BACKGROUND: Adenocarcinoma of the lung with EML4-ALK translocation is a rare subtype of Non Small-Cell Lung Cancer (NSCLC) that has recently shown to benefit from treatment with crizotinib.	Crizotinib	178-188	EMAP like 4	Homo sapiens	44-48
25178493-1	2014	BACKGROUND: Adenocarcinoma of the lung with EML4-ALK translocation is a rare subtype of Non Small-Cell Lung Cancer (NSCLC) that has recently shown to benefit from treatment with crizotinib.	Crizotinib	178-188	ALK receptor tyrosine kinase	Homo sapiens	49-52
25178493-5	2014	CONCLUSION: We suggest crizotinib may be active over choroidal metastases in a patient harboring ALK translocation with no need of radiotherapy.	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	97-100
24750504-2	2014	Crizotinib, an inhibitor of ALK-fusion proteins, has shown clinical activity, but resistance mechanisms limit long-lasting disease control.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	28-31
24887559-0	2014	Selective ALK inhibitor alectinib with potent antitumor activity in models of crizotinib resistance.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	10-13
24887559-1	2014	The clinical efficacy of the ALK inhibitor crizotinib has been demonstrated in ALK fusion-positive NSCLC; however, resistance to crizotinib certainly occurs through ALK secondary mutations in clinical use.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	29-32
24887559-1	2014	The clinical efficacy of the ALK inhibitor crizotinib has been demonstrated in ALK fusion-positive NSCLC; however, resistance to crizotinib certainly occurs through ALK secondary mutations in clinical use.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	79-82
24887559-1	2014	The clinical efficacy of the ALK inhibitor crizotinib has been demonstrated in ALK fusion-positive NSCLC; however, resistance to crizotinib certainly occurs through ALK secondary mutations in clinical use.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	79-82
24887559-1	2014	The clinical efficacy of the ALK inhibitor crizotinib has been demonstrated in ALK fusion-positive NSCLC; however, resistance to crizotinib certainly occurs through ALK secondary mutations in clinical use.	Crizotinib	129-139	ALK receptor tyrosine kinase	Homo sapiens	29-32
24887559-5	2014	These results demonstrated that alectinib might provide therapeutic opportunities for crizotinib-treated patients with ALK secondary mutations.	Crizotinib	86-96	ALK receptor tyrosine kinase	Homo sapiens	119-122
25135623-2	2014	Activating anaplastic lymphoma kinase (ALK)-gene rearrangement has been detected in 3-7 % of NSCLC cases, and the ALK inhibitor crizotinib is now an approved treatment for patients with tumors harboring this event.	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	11-37
25135623-2	2014	Activating anaplastic lymphoma kinase (ALK)-gene rearrangement has been detected in 3-7 % of NSCLC cases, and the ALK inhibitor crizotinib is now an approved treatment for patients with tumors harboring this event.	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	39-42
25135623-2	2014	Activating anaplastic lymphoma kinase (ALK)-gene rearrangement has been detected in 3-7 % of NSCLC cases, and the ALK inhibitor crizotinib is now an approved treatment for patients with tumors harboring this event.	Crizotinib	128-138	ALK receptor tyrosine kinase	Homo sapiens	114-117
25299566-0	2014	[ALK-rearranged non-small cell lung cancer: how to optimize treatment with crizotinib in routine practice?].	Crizotinib	75-85	ALK receptor tyrosine kinase	Homo sapiens	1-4
25299566-1	2014	Crizotinib (XALKORI( ), Pfizer) is a tyrosine kinase inhibitor of ALK, MET, and ROS1, which is currently approved for the second line treatment for ALK-rearranged lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	13-16
25299566-1	2014	Crizotinib (XALKORI( ), Pfizer) is a tyrosine kinase inhibitor of ALK, MET, and ROS1, which is currently approved for the second line treatment for ALK-rearranged lung cancer.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	80-84
25299566-1	2014	Crizotinib (XALKORI( ), Pfizer) is a tyrosine kinase inhibitor of ALK, MET, and ROS1, which is currently approved for the second line treatment for ALK-rearranged lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	66-69
25299566-11	2014	To conclude, these practical elements are helpful to optimize treatment with crizotinib in patients with ALK-rearranged lung cancer; in the future, academic initiatives should be taken to study these aspects, based on the monitoring of large cohorts of patients treated with crizotinib.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	105-108
25541622-2	2014	ALK targeted therapies such as crizotinib increase survival benefit in this patient population.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	0-3
24984564-3	2014	Preclinical and single-arm phase I studies have shown that patients with ALK-rearranged non-small cell lung cancer (NSCLC) can be successfully treated with crizotinib.	Crizotinib	156-166	ALK receptor tyrosine kinase	Homo sapiens	73-76
24984564-4	2014	Furthermore, a phase III randomized study indicated that crizotinib is superior to standard chemotherapy in the treatment of patients with NSCLC harboring the ALK rearrangement who had received 1 previous platinum-based chemotherapy.	Crizotinib	57-67	ALK receptor tyrosine kinase	Homo sapiens	159-162
24984564-5	2014	Despite the excellent efficacy of crizotinib in patients with ALK-positive (ALK(+)) lung cancer, resistance mechanisms--such as secondary mutations in the ALK gene, the activation of other oncogenes, and so on--have been identified as conferring resistance to crizotinib.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	62-65
24984564-5	2014	Despite the excellent efficacy of crizotinib in patients with ALK-positive (ALK(+)) lung cancer, resistance mechanisms--such as secondary mutations in the ALK gene, the activation of other oncogenes, and so on--have been identified as conferring resistance to crizotinib.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	76-79
24984564-5	2014	Despite the excellent efficacy of crizotinib in patients with ALK-positive (ALK(+)) lung cancer, resistance mechanisms--such as secondary mutations in the ALK gene, the activation of other oncogenes, and so on--have been identified as conferring resistance to crizotinib.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	76-79
24984564-6	2014	Second-generation ALK inhibitors, such as alectinib and ceritinib, have been shown to be effective not only in crizotinib-naive patients but also in those resistant to crizotinib.	Crizotinib	111-121	ALK receptor tyrosine kinase	Homo sapiens	18-21
24984564-6	2014	Second-generation ALK inhibitors, such as alectinib and ceritinib, have been shown to be effective not only in crizotinib-naive patients but also in those resistant to crizotinib.	Crizotinib	168-178	ALK receptor tyrosine kinase	Homo sapiens	18-21
24984564-9	2014	Is crizotinib just a first-generation ALK inhibitor?	Crizotinib	3-13	ALK receptor tyrosine kinase	Homo sapiens	38-41
25028698-0	2014	A case report of epithelioid inflammatory myofibroblastic sarcoma with RANBP2-ALK fusion gene treated with the ALK inhibitor, crizotinib.	Crizotinib	126-136	RAN binding protein 2	Homo sapiens	71-77
25028698-0	2014	A case report of epithelioid inflammatory myofibroblastic sarcoma with RANBP2-ALK fusion gene treated with the ALK inhibitor, crizotinib.	Crizotinib	126-136	ALK receptor tyrosine kinase	Homo sapiens	78-81
25028698-0	2014	A case report of epithelioid inflammatory myofibroblastic sarcoma with RANBP2-ALK fusion gene treated with the ALK inhibitor, crizotinib.	Crizotinib	126-136	ALK receptor tyrosine kinase	Homo sapiens	111-114
25153538-0	2014	Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	117-120
25153538-1	2014	BACKGROUND: Patients with non-small-cell lung cancer (NSCLC) and ALK rearrangements generally have a progression-free survival of 8-11 months while on treatment with the ALK inhibitor crizotinib.	Crizotinib	184-194	ALK receptor tyrosine kinase	Homo sapiens	65-68
25153538-1	2014	BACKGROUND: Patients with non-small-cell lung cancer (NSCLC) and ALK rearrangements generally have a progression-free survival of 8-11 months while on treatment with the ALK inhibitor crizotinib.	Crizotinib	184-194	ALK receptor tyrosine kinase	Homo sapiens	170-173
25153538-4	2014	Alectinib is a novel, highly selective, and potent ALK inhibitor that has shown clinical activity in patients with crizotinib-naive ALK-rearranged NSCLC.	Crizotinib	115-125	ALK receptor tyrosine kinase	Homo sapiens	51-54
25153538-6	2014	METHODS: We enrolled patients with ALK-rearranged NSCLC who progressed on or were intolerant to crizotinib.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	35-38
24850290-0	2014	Reduction of leukemia cell burden and restoration of normal hematopoiesis at 3 months of crizotinib treatment in RAN-binding protein 2 (RANBP2)-anaplastic lymphoma kinase (ALK) acute myeloid leukemia.	Crizotinib	89-99	RAN binding protein 2	Homo sapiens	113-134
24850290-0	2014	Reduction of leukemia cell burden and restoration of normal hematopoiesis at 3 months of crizotinib treatment in RAN-binding protein 2 (RANBP2)-anaplastic lymphoma kinase (ALK) acute myeloid leukemia.	Crizotinib	89-99	RAN binding protein 2	Homo sapiens	136-142
24850290-0	2014	Reduction of leukemia cell burden and restoration of normal hematopoiesis at 3 months of crizotinib treatment in RAN-binding protein 2 (RANBP2)-anaplastic lymphoma kinase (ALK) acute myeloid leukemia.	Crizotinib	89-99	ALK receptor tyrosine kinase	Homo sapiens	172-175
25173427-1	2014	Crizotinib, a selective tyrosine kinase inhibitor (TKI), shows marked activity in patients whose lung cancers harbor fusions in the gene encoding anaplastic lymphoma receptor tyrosine kinase (ALK), but its efficacy is limited by variable primary responses and acquired resistance.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	146-190
25173427-1	2014	Crizotinib, a selective tyrosine kinase inhibitor (TKI), shows marked activity in patients whose lung cancers harbor fusions in the gene encoding anaplastic lymphoma receptor tyrosine kinase (ALK), but its efficacy is limited by variable primary responses and acquired resistance.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	192-195
25173427-5	2014	Consistent with this finding, the levels of IGF-1R and IRS-1 are increased in biopsy samples from patients progressing on crizotinib monotherapy.	Crizotinib	122-132	insulin like growth factor 1 receptor	Homo sapiens	44-50
25173427-5	2014	Consistent with this finding, the levels of IGF-1R and IRS-1 are increased in biopsy samples from patients progressing on crizotinib monotherapy.	Crizotinib	122-132	insulin receptor substrate 1	Homo sapiens	55-60
25228590-6	2014	Combined treatment with crizotinib and an ATP-competitive mTOR inhibitor abrogated RPS6 phosphorylation, leading to reduced tumor growth and prolonged survival in ALK(F1174L)/MYCN-positive models compared to single agent treatment.	Crizotinib	24-34	MYCN proto-oncogene, bHLH transcription factor	Homo sapiens	175-179
25228590-8	2014	Here, an inhibitor with potency against both mTOR and PI3K was more effective in promoting cytotoxicity when combined with crizotinib.	Crizotinib	123-133	mechanistic target of rapamycin kinase	Homo sapiens	45-49
26767038-3	2014	We enrolled the patient in an off-label program for the treatment of ROS1 rearranged adenocarcinomas with the EML4/anaplastic lymphoma kinase inhibitor crizotinib.	Crizotinib	152-162	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	69-73
26767038-3	2014	We enrolled the patient in an off-label program for the treatment of ROS1 rearranged adenocarcinomas with the EML4/anaplastic lymphoma kinase inhibitor crizotinib.	Crizotinib	152-162	EMAP like 4	Homo sapiens	110-114
24456475-2	2014	Recently, chromosomal rearrangements involving c-ros oncogene 1, receptor tyrosine kinase (ROS1) were identified, and patients seem to benefit from crizotinib treatment.	Crizotinib	148-158	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	47-89
24853389-3	2014	The first-in-class tyrosine kinase inhibitor crizotinib is effective against ALK-positive NSCLC and is currently used as first-line or salvage therapy in the setting of advanced disease.	Crizotinib	45-55	ALK receptor tyrosine kinase	Homo sapiens	77-80
24853389-6	2014	Potent second-generation ALK inhibitors currently in trials are producing encouraging results in ALK-positive NSCLC, even in patients with acquired resistance to crizotinib.	Crizotinib	162-172	ALK receptor tyrosine kinase	Homo sapiens	25-28
28210140-3	2014	The most recently identified molecular target is the anaplastic lymphoma kinase (ALK) gene rearrangement, and patient responses to the ALK inhibitor crizotinib have led to its approval in this selected patient population.	Crizotinib	149-159	ALK receptor tyrosine kinase	Homo sapiens	53-79
28210140-3	2014	The most recently identified molecular target is the anaplastic lymphoma kinase (ALK) gene rearrangement, and patient responses to the ALK inhibitor crizotinib have led to its approval in this selected patient population.	Crizotinib	149-159	ALK receptor tyrosine kinase	Homo sapiens	81-84
28210140-3	2014	The most recently identified molecular target is the anaplastic lymphoma kinase (ALK) gene rearrangement, and patient responses to the ALK inhibitor crizotinib have led to its approval in this selected patient population.	Crizotinib	149-159	ALK receptor tyrosine kinase	Homo sapiens	135-138
24875859-6	2014	Molecular tumor profiling revealed a ROS1 fusion, and he had a dramatic response to the ROS1 inhibitor crizotinib.	Crizotinib	103-113	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	37-41
24875859-6	2014	Molecular tumor profiling revealed a ROS1 fusion, and he had a dramatic response to the ROS1 inhibitor crizotinib.	Crizotinib	103-113	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	88-92
24456475-2	2014	Recently, chromosomal rearrangements involving c-ros oncogene 1, receptor tyrosine kinase (ROS1) were identified, and patients seem to benefit from crizotinib treatment.	Crizotinib	148-158	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	91-95
24889366-5	2014	The identification of anaplastic lymphoma kinase (ALK) rearrangements in 2-5% of NSCLC patients led to the rapid clinical development of its oral TKI, crizotinib, also targeting the proto-oncogene MET and ROS1.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	22-48
24859689-2	2014	The recent availability of crizotinib in clinical practice, for the treatment of patients with advanced non-small cell lung cancer (NSCLC) selected by the presence of anaplastic lymphoma kinase (ALK) rearrangement, has relevant implications for both the diagnostic phase and the treatment choices.	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	167-193
24889366-5	2014	The identification of anaplastic lymphoma kinase (ALK) rearrangements in 2-5% of NSCLC patients led to the rapid clinical development of its oral TKI, crizotinib, also targeting the proto-oncogene MET and ROS1.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	50-53
24859689-2	2014	The recent availability of crizotinib in clinical practice, for the treatment of patients with advanced non-small cell lung cancer (NSCLC) selected by the presence of anaplastic lymphoma kinase (ALK) rearrangement, has relevant implications for both the diagnostic phase and the treatment choices.	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	195-198
24859689-3	2014	In the United States, crizotinib was approved by the Food and Drug Administration (FDA) in 2011 for patients with ALK positivity detected by FDA-approved companion diagnostic test.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	114-117
24889366-5	2014	The identification of anaplastic lymphoma kinase (ALK) rearrangements in 2-5% of NSCLC patients led to the rapid clinical development of its oral TKI, crizotinib, also targeting the proto-oncogene MET and ROS1.	Crizotinib	151-161	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	205-209
24859689-5	2014	In Europe, European Medicines Agency (EMA) approved crizotinib for ALK-positive patients in 2012, without specifying the type of test used for determining the positivity.	Crizotinib	52-62	ALK receptor tyrosine kinase	Homo sapiens	67-70
24889366-6	2014	The results reported from the first phase III trial showed superiority of crizotinib compared with standard chemotherapy in second-line treatment of ALK-positive NSCLC, which was recently approved in several countries in this setting.	Crizotinib	74-84	ALK receptor tyrosine kinase	Homo sapiens	149-152
24859689-7	2014	Given the robust evidence of activity of crizotinib in ALK-positive patients both pretreated and chemotherapy-naive, and the favourable tolerability profile of the drug, many oncologists would prefer to administer the drug as early as possible.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	55-58
24859689-8	2014	This is technically feasible in the United States, where crizotinib was approved well before the availability of the results of the randomized phase III trial comparing the drug with standard second-line chemotherapy, and the use of crizotinib in ALK-positive patients is not restricted to a specific line of treatment.	Crizotinib	233-243	ALK receptor tyrosine kinase	Homo sapiens	247-250
24885982-6	2014	A similar analysis was performed to identify a biomarker associated with shorter progression-free survival (PFS) after therapy with the ALK inhibitor crizotinib.	Crizotinib	150-160	ALK receptor tyrosine kinase	Homo sapiens	136-139
24859689-10	2014	In both realities, a deeper knowledge of mechanisms of resistance, the role of repeated biopsies, the treatment strategy for patients experiencing disease progression with crizotinib, the choice of the best chemotherapy regimen are challenging topics for the management of ALK-positive patients in clinical practice.	Crizotinib	172-182	ALK receptor tyrosine kinase	Homo sapiens	273-276
24854402-0	2014	Overcoming crizotinib resistance in ALK-rearranged non-small cell lung cancer.	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	36-39
24929890-8	2014	However, we provide evidence that the cytotoxic effect of crizotinib in our cell line model correlates with its ability to inhibit P-glycoprotein (ABCB1)-associated transport functions.	Crizotinib	58-68	ATP binding cassette subfamily B member 1	Homo sapiens	147-152
25806308-3	2014	The discovery of the EML4-ALK fusion gene in a subgroup of patients with NSCLC and the subsequent clinical development of crizotinib has been an amazing success story in lung cancer translational-research, and its accelerated approval [only 4 years from the discovery of ALK rearrangement in NSCLC to the approval by the Food and Drug Administration (FDA)] marked the beginning of the new decade of targeted therapy.	Crizotinib	122-132	ALK receptor tyrosine kinase	Homo sapiens	271-274
25806308-7	2014	The inhibition of the molecular chaperone, HSP90, represents another promising strategy to overcome crizotinib resistance in ALK-rearranged NSCLC.	Crizotinib	100-110	heat shock protein 90 alpha family class A member 1	Homo sapiens	43-48
25806308-7	2014	The inhibition of the molecular chaperone, HSP90, represents another promising strategy to overcome crizotinib resistance in ALK-rearranged NSCLC.	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	125-128
25026277-5	2014	ASP3026 is a second-generation ALK inhibitor that can overcome crizotinib resistance in non-small cell lung cancer, and is currently being evaluated in clinical trials of patients with ALK+ solid tumors.	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	31-34
25026277-9	2014	In addition, ASP3026 significantly reduced the proliferation of 293T cells transfected with NPM-ALK mutants that are resistant to crizotinib and downregulated tyrosine phosphorylation of these mutants.	Crizotinib	130-140	nucleophosmin 1	Homo sapiens	92-95
25026277-9	2014	In addition, ASP3026 significantly reduced the proliferation of 293T cells transfected with NPM-ALK mutants that are resistant to crizotinib and downregulated tyrosine phosphorylation of these mutants.	Crizotinib	130-140	ALK receptor tyrosine kinase	Homo sapiens	96-99
25058391-1	2014	ROS1 rearrangement is a predictive biomarker for response to the tyrosine kinase inhibitor, crizotinib.	Crizotinib	92-102	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	0-4
25232318-0	2014	Durable Response to Crizotinib in a MET-Amplified, KRAS-Mutated Carcinoma of Unknown Primary.	Crizotinib	20-30	KRAS proto-oncogene, GTPase	Homo sapiens	51-55
25033171-0	2014	P-loop conformation governed crizotinib resistance in G2032R-mutated ROS1 tyrosine kinase: clues from free energy landscape.	Crizotinib	29-39	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	69-73
25033171-4	2014	For example, recently, an acquired secondary mutation, G2032R, has been detected in the drug target, ROS1 tyrosine kinase, from a crizotinib-resistant patient, who responded poorly to crizotinib within a very short therapeutic term.	Crizotinib	130-140	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	101-105
25033171-4	2014	For example, recently, an acquired secondary mutation, G2032R, has been detected in the drug target, ROS1 tyrosine kinase, from a crizotinib-resistant patient, who responded poorly to crizotinib within a very short therapeutic term.	Crizotinib	184-194	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	101-105
25033171-7	2014	Here, free energy surfaces were characterized by the drug-target distance and the phosphate-binding loop (P-loop) conformational change of the crizotinib-ROS1 complex through advanced molecular dynamics techniques, and it was revealed that the more rigid P-loop region in the G2032R-mutated ROS1 was primarily responsible for the crizotinib resistance, which on one hand, impaired the binding of crizotinib directly, and on the other hand, shortened the residence time induced by the flattened free energy surface.	Crizotinib	143-153	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	154-158
25033171-7	2014	Here, free energy surfaces were characterized by the drug-target distance and the phosphate-binding loop (P-loop) conformational change of the crizotinib-ROS1 complex through advanced molecular dynamics techniques, and it was revealed that the more rigid P-loop region in the G2032R-mutated ROS1 was primarily responsible for the crizotinib resistance, which on one hand, impaired the binding of crizotinib directly, and on the other hand, shortened the residence time induced by the flattened free energy surface.	Crizotinib	143-153	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	291-295
25033171-7	2014	Here, free energy surfaces were characterized by the drug-target distance and the phosphate-binding loop (P-loop) conformational change of the crizotinib-ROS1 complex through advanced molecular dynamics techniques, and it was revealed that the more rigid P-loop region in the G2032R-mutated ROS1 was primarily responsible for the crizotinib resistance, which on one hand, impaired the binding of crizotinib directly, and on the other hand, shortened the residence time induced by the flattened free energy surface.	Crizotinib	330-340	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	154-158
25033171-7	2014	Here, free energy surfaces were characterized by the drug-target distance and the phosphate-binding loop (P-loop) conformational change of the crizotinib-ROS1 complex through advanced molecular dynamics techniques, and it was revealed that the more rigid P-loop region in the G2032R-mutated ROS1 was primarily responsible for the crizotinib resistance, which on one hand, impaired the binding of crizotinib directly, and on the other hand, shortened the residence time induced by the flattened free energy surface.	Crizotinib	330-340	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	154-158
24992725-1	2014	EML4-ALK is a new driver gene of non-small cell lung cancer and a target of crizotinib.	Crizotinib	76-86	EMAP like 4	Homo sapiens	0-4
24992725-1	2014	EML4-ALK is a new driver gene of non-small cell lung cancer and a target of crizotinib.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	5-8
24129617-3	2014	The best compound 6f showed good activity against wild-type ALK along with crizotinib-resistant mutant ALK, and it showed 6 times better activity in cell-based assay than crizotinib.	Crizotinib	75-85	ALK receptor tyrosine kinase	Homo sapiens	103-106
25322323-0	2014	ALK inhibitors in non-small cell lung cancer: crizotinib and beyond.	Crizotinib	46-56	ALK receptor tyrosine kinase	Homo sapiens	0-3
25322323-1	2014	The treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring chromosomal rearrangements of anaplastic lymphoma kinase (ALK) has been revolutionized by the development of crizotinib, a small molecule inhibitor of the tyrosine kinases ALK, ROS1, and MET.	Crizotinib	194-204	ALK receptor tyrosine kinase	Homo sapiens	115-141
25322323-1	2014	The treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring chromosomal rearrangements of anaplastic lymphoma kinase (ALK) has been revolutionized by the development of crizotinib, a small molecule inhibitor of the tyrosine kinases ALK, ROS1, and MET.	Crizotinib	194-204	ALK receptor tyrosine kinase	Homo sapiens	143-146
25322323-1	2014	The treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring chromosomal rearrangements of anaplastic lymphoma kinase (ALK) has been revolutionized by the development of crizotinib, a small molecule inhibitor of the tyrosine kinases ALK, ROS1, and MET.	Crizotinib	194-204	ALK receptor tyrosine kinase	Homo sapiens	257-260
25322323-1	2014	The treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring chromosomal rearrangements of anaplastic lymphoma kinase (ALK) has been revolutionized by the development of crizotinib, a small molecule inhibitor of the tyrosine kinases ALK, ROS1, and MET.	Crizotinib	194-204	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	262-266
25101329-3	2014	Crizotinib is now recognized as the standard of care in chemotherapy-pretreated ALK-positive NSCLC due to the positive results of a recently published trial.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	80-83
24952065-5	2014	MD results showed that the average atom, especially atoms of the native-type ALK-crizotinib complex, movements were less, displayed less fluctuation, fast convergence of energy, and changes in geometry.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	77-80
24952065-6	2014	This shows the stable binding of crizotinib with the native-type ALK in comparison to the mutant-type ALK.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	65-68
24952065-6	2014	This shows the stable binding of crizotinib with the native-type ALK in comparison to the mutant-type ALK.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	102-105
25669042-8	2014	In addition, NSCLCs with the anaplastic lymphoma kinase (ALK) fusion gene are highly responsive to an ALK inhibitor, crizotinib.	Crizotinib	117-127	ALK receptor tyrosine kinase	Homo sapiens	29-55
25669042-8	2014	In addition, NSCLCs with the anaplastic lymphoma kinase (ALK) fusion gene are highly responsive to an ALK inhibitor, crizotinib.	Crizotinib	117-127	ALK receptor tyrosine kinase	Homo sapiens	57-60
25669042-8	2014	In addition, NSCLCs with the anaplastic lymphoma kinase (ALK) fusion gene are highly responsive to an ALK inhibitor, crizotinib.	Crizotinib	117-127	ALK receptor tyrosine kinase	Homo sapiens	102-105
24819116-1	2014	Although crizotinib demonstrates robust efficacy in anaplastic lymphoma kinase (ALK)-positive non-small-cell lung carcinoma patients, progression during treatment eventually develops.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	52-78
24819116-1	2014	Although crizotinib demonstrates robust efficacy in anaplastic lymphoma kinase (ALK)-positive non-small-cell lung carcinoma patients, progression during treatment eventually develops.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	80-83
24878018-1	2014	CONTEXT: Echinoderm microtubule-associated protein-like 4 gene (EML4) and anaplastic lymphoma kinase gene (ALK) fusion was shown to be the driver of tumorigenesis in approximately 3% to 5% of patients with non-small cell lung cancer (NSCLC) and is associated with response to inhibition with crizotinib.	Crizotinib	292-302	EMAP like 4	Homo sapiens	9-57
24878018-1	2014	CONTEXT: Echinoderm microtubule-associated protein-like 4 gene (EML4) and anaplastic lymphoma kinase gene (ALK) fusion was shown to be the driver of tumorigenesis in approximately 3% to 5% of patients with non-small cell lung cancer (NSCLC) and is associated with response to inhibition with crizotinib.	Crizotinib	292-302	EMAP like 4	Homo sapiens	64-68
24878018-1	2014	CONTEXT: Echinoderm microtubule-associated protein-like 4 gene (EML4) and anaplastic lymphoma kinase gene (ALK) fusion was shown to be the driver of tumorigenesis in approximately 3% to 5% of patients with non-small cell lung cancer (NSCLC) and is associated with response to inhibition with crizotinib.	Crizotinib	292-302	ALK receptor tyrosine kinase	Homo sapiens	107-110
24675041-0	2014	The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	4-7
24675041-1	2014	UNLABELLED: Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements invariably develop resistance to the ALK tyrosine kinase inhibitor (TKI) crizotinib.	Crizotinib	184-194	ALK receptor tyrosine kinase	Homo sapiens	58-84
24675041-1	2014	UNLABELLED: Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements invariably develop resistance to the ALK tyrosine kinase inhibitor (TKI) crizotinib.	Crizotinib	184-194	ALK receptor tyrosine kinase	Homo sapiens	86-89
24675041-1	2014	UNLABELLED: Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements invariably develop resistance to the ALK tyrosine kinase inhibitor (TKI) crizotinib.	Crizotinib	184-194	ALK receptor tyrosine kinase	Homo sapiens	148-151
24675041-2	2014	Herein, we report the first preclinical evaluation of the next-generation ALK TKI, ceritinib (LDK378), in the setting of crizotinib resistance.	Crizotinib	121-131	ALK receptor tyrosine kinase	Homo sapiens	74-77
24675041-7	2014	SIGNIFICANCE: The second-generation ALK inhibitor ceritinib can overcome several crizotinib-resistant mutations and is potent against several in vitro and in vivo laboratory models of acquired resistance to crizotinib.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	36-39
24675041-7	2014	SIGNIFICANCE: The second-generation ALK inhibitor ceritinib can overcome several crizotinib-resistant mutations and is potent against several in vitro and in vivo laboratory models of acquired resistance to crizotinib.	Crizotinib	207-217	ALK receptor tyrosine kinase	Homo sapiens	36-39
24675041-8	2014	These findings provide the molecular basis for the marked clinical activity of ceritinib in patients with ALK-positive NSCLC with crizotinib-resistant disease.	Crizotinib	130-140	ALK receptor tyrosine kinase	Homo sapiens	106-109
24478382-2	2014	Preliminary results from clinical trials suggest that patients with ALK fusion positive cancers might optimally benefit from the tyrosine kinase inhibitor crizotinib, but a comprehensive analysis of solid tumour types for ALK fusion and fusion associated expression is lacking.	Crizotinib	155-165	ALK receptor tyrosine kinase	Homo sapiens	68-71
24929890-3	2014	RESULTS: We identified the MNNG HOS transforming gene (MET)-anaplastic lymphoma receptor tyrosine kinase (ALK) inhibitor crizotinib as the top hit of our drug screen, whereas compounds targeting the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway showed no or only minor in vitro activity.	Crizotinib	121-131	ALK receptor tyrosine kinase	Homo sapiens	106-109
24929890-3	2014	RESULTS: We identified the MNNG HOS transforming gene (MET)-anaplastic lymphoma receptor tyrosine kinase (ALK) inhibitor crizotinib as the top hit of our drug screen, whereas compounds targeting the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway showed no or only minor in vitro activity.	Crizotinib	121-131	vascular endothelial growth factor A	Homo sapiens	235-239
24929890-3	2014	RESULTS: We identified the MNNG HOS transforming gene (MET)-anaplastic lymphoma receptor tyrosine kinase (ALK) inhibitor crizotinib as the top hit of our drug screen, whereas compounds targeting the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway showed no or only minor in vitro activity.	Crizotinib	121-131	mechanistic target of rapamycin kinase	Homo sapiens	244-273
24929890-3	2014	RESULTS: We identified the MNNG HOS transforming gene (MET)-anaplastic lymphoma receptor tyrosine kinase (ALK) inhibitor crizotinib as the top hit of our drug screen, whereas compounds targeting the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway showed no or only minor in vitro activity.	Crizotinib	121-131	mechanistic target of rapamycin kinase	Homo sapiens	275-279
24952065-1	2014	Crizotinib is the most effective and the only drug that has been approved for the treatment of anaplastic lymphoma kinase (ALK)-positive lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	95-121
24952065-1	2014	Crizotinib is the most effective and the only drug that has been approved for the treatment of anaplastic lymphoma kinase (ALK)-positive lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	123-126
24952065-2	2014	Reports suggest that there is a development of an acquired resistance against crizotinib action due to the emergence of several mutations in the ALK gene and F1174L is one such mutation.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	145-148
24952065-4	2014	Docking results suggest that crizotinib was found to adopt the most promising conformations to the native-type ALK by identifying the M1199 residue as a prospective partner for making a hydrogen bond as compared to the mutant-type ALK.	Crizotinib	29-39	ALK receptor tyrosine kinase	Homo sapiens	111-114
24952065-4	2014	Docking results suggest that crizotinib was found to adopt the most promising conformations to the native-type ALK by identifying the M1199 residue as a prospective partner for making a hydrogen bond as compared to the mutant-type ALK.	Crizotinib	29-39	ALK receptor tyrosine kinase	Homo sapiens	231-234
24940496-3	2014	It was demonstrated that ALK-positive NSCLCs exhibit a high response rate to the ALK inhibitor crizotinib.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	25-28
24940496-3	2014	It was demonstrated that ALK-positive NSCLCs exhibit a high response rate to the ALK inhibitor crizotinib.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	81-84
24940496-4	2014	This is the case report of a patient with NSCLC harboring EML4-ALK rearrangement, who experienced slowly progressive disease within 4 years of maintenance treatment with pemetrexed and later exhibited a marked response to crizotinib.	Crizotinib	222-232	EMAP like 4	Homo sapiens	58-62
24940496-4	2014	This is the case report of a patient with NSCLC harboring EML4-ALK rearrangement, who experienced slowly progressive disease within 4 years of maintenance treatment with pemetrexed and later exhibited a marked response to crizotinib.	Crizotinib	222-232	ALK receptor tyrosine kinase	Homo sapiens	63-66
24648382-2	2014	Patients who are positive for ALK rearrangements may be successfully treated with the ALK inhibitor crizotinib.	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	30-33
24648382-2	2014	Patients who are positive for ALK rearrangements may be successfully treated with the ALK inhibitor crizotinib.	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	86-89
24745764-6	2014	New agents targeting EGFR or ALK are under evaluation particularly in individuals with acquired resistance to EGFR TKIs or crizotinib.	Crizotinib	123-133	epidermal growth factor receptor	Homo sapiens	21-25
24745764-6	2014	New agents targeting EGFR or ALK are under evaluation particularly in individuals with acquired resistance to EGFR TKIs or crizotinib.	Crizotinib	123-133	ALK receptor tyrosine kinase	Homo sapiens	29-32
24885982-11	2014	CONCLUSION: ALK+ NSCLC has distinct characteristics at CT imaging that, when combined with clinical covariates, discriminate ALK+ from non-ALK tumors and can potentially identify patients with a shorter durable response to crizotinib.	Crizotinib	223-233	ALK receptor tyrosine kinase	Homo sapiens	12-15
24688086-5	2014	After chromosomal rearrangement of echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene was detected in this adenocarcinoma, he responded to treatment with crizotinib.	Crizotinib	197-207	EMAP like 4	Homo sapiens	35-83
24787965-1	2014	INTRODUCTION: Detection of the ALK rearrangement in a solid tumor gives these patients the option of crizotinib as an oral form of anticancer treatment.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	31-34
24828661-6	2014	RESULTS: Crizotinib and TAS-115 inhibited Met phosphorylation and reversed erlotinib resistance and VEGF production triggered by HGF in PC-9 and HCC827 cells in vitro.	Crizotinib	9-19	vascular endothelial growth factor A	Homo sapiens	100-104
24828661-6	2014	RESULTS: Crizotinib and TAS-115 inhibited Met phosphorylation and reversed erlotinib resistance and VEGF production triggered by HGF in PC-9 and HCC827 cells in vitro.	Crizotinib	9-19	hepatocyte growth factor	Homo sapiens	129-132
24828661-6	2014	RESULTS: Crizotinib and TAS-115 inhibited Met phosphorylation and reversed erlotinib resistance and VEGF production triggered by HGF in PC-9 and HCC827 cells in vitro.	Crizotinib	9-19	proprotein convertase subtilisin/kexin type 9	Homo sapiens	136-140
24828670-0	2014	A case of large-cell neuroendocrine carcinoma harboring an EML4-ALK rearrangement with resistance to the ALK inhibitor crizotinib.	Crizotinib	119-129	EMAP like 4	Homo sapiens	59-63
24828670-0	2014	A case of large-cell neuroendocrine carcinoma harboring an EML4-ALK rearrangement with resistance to the ALK inhibitor crizotinib.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	64-67
24828670-0	2014	A case of large-cell neuroendocrine carcinoma harboring an EML4-ALK rearrangement with resistance to the ALK inhibitor crizotinib.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	105-108
24633422-10	2014	The EML4-ALK translocation has been reported in approximately 5 % of lung cancers, as well as in pediatric neuroblastoma, and is a therapeutic target for crizotinib.	Crizotinib	154-164	EMAP like 4	Homo sapiens	4-8
24633422-10	2014	The EML4-ALK translocation has been reported in approximately 5 % of lung cancers, as well as in pediatric neuroblastoma, and is a therapeutic target for crizotinib.	Crizotinib	154-164	ALK receptor tyrosine kinase	Homo sapiens	9-12
24885608-9	2014	Once crizotinib was approved by the China Food and Drug Administration and the ALK gene translocation was identified in tumor cells by fluorescent in situ hybridization, the patient commenced treatment with crizotinib.	Crizotinib	5-15	ALK receptor tyrosine kinase	Homo sapiens	79-82
24885608-9	2014	Once crizotinib was approved by the China Food and Drug Administration and the ALK gene translocation was identified in tumor cells by fluorescent in situ hybridization, the patient commenced treatment with crizotinib.	Crizotinib	207-217	ALK receptor tyrosine kinase	Homo sapiens	79-82
24885608-1	2014	BACKGROUND: The discovery of the fusion gene echinodermmicro tubule associated proteinlike 4-anaplastic lymphoma kinase, EML4-ALK, in patients with non-small-cell lung cancer has led to the remarkable development of anaplastic lymphoma kinase inhibitors, such as crizotinib.	Crizotinib	263-273	EMAP like 4	Homo sapiens	121-125
24811913-5	2014	We show that tumors expressing the R1279Q mutation are sensitive to ALK inhibition upon crizotinib treatment.	Crizotinib	88-98	anaplastic lymphoma kinase	Mus musculus	68-71
24885608-1	2014	BACKGROUND: The discovery of the fusion gene echinodermmicro tubule associated proteinlike 4-anaplastic lymphoma kinase, EML4-ALK, in patients with non-small-cell lung cancer has led to the remarkable development of anaplastic lymphoma kinase inhibitors, such as crizotinib.	Crizotinib	263-273	ALK receptor tyrosine kinase	Homo sapiens	126-129
24885608-3	2014	Herein, we report the case of a woman with ALK gene translocation-squamous cell lung cancer who experienced a remarkable tumor response to crizotinib after two courses of failed chemotherapy.	Crizotinib	139-149	ALK receptor tyrosine kinase	Homo sapiens	43-46
24556908-0	2014	Induction of autophagy contributes to crizotinib resistance in ALK-positive lung cancer.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	63-66
24556908-1	2014	Use of the inhibitor of ALK fusion onco-protein, crizotinib (PF02341066), has achieved impressive clinical efficacy in patients with ALK-positive non-small cell lung cancer.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	24-27
24556908-1	2014	Use of the inhibitor of ALK fusion onco-protein, crizotinib (PF02341066), has achieved impressive clinical efficacy in patients with ALK-positive non-small cell lung cancer.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	133-136
24556908-4	2014	We observed that ALK was downregulated in the crizotinib-resistant lung cancer cell line, H3122CR-1, and this was causally associated with autophagy induction.	Crizotinib	46-56	ALK receptor tyrosine kinase	Homo sapiens	17-20
24556908-6	2014	Activation of autophagy in crizotinib-resistant H3122CR-1 cells involved alteration of the Akt/mTOR signaling pathway.	Crizotinib	27-37	AKT serine/threonine kinase 1	Homo sapiens	91-94
24556908-6	2014	Activation of autophagy in crizotinib-resistant H3122CR-1 cells involved alteration of the Akt/mTOR signaling pathway.	Crizotinib	27-37	mechanistic target of rapamycin kinase	Homo sapiens	95-99
24695225-0	2014	Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy.	Crizotinib	36-50	nudix hydrolase 1	Homo sapiens	28-32
24722154-3	2014	However, the deregulation of MET/HGF pathway in NSCLC harboring ALK gene rearrangement (ALK[+]), which is sensitive to dual ALK and MET inhibitor Crizotinib, has not been reported.	Crizotinib	146-156	hepatocyte growth factor	Homo sapiens	33-36
24722154-3	2014	However, the deregulation of MET/HGF pathway in NSCLC harboring ALK gene rearrangement (ALK[+]), which is sensitive to dual ALK and MET inhibitor Crizotinib, has not been reported.	Crizotinib	146-156	ALK receptor tyrosine kinase	Homo sapiens	64-67
24722154-3	2014	However, the deregulation of MET/HGF pathway in NSCLC harboring ALK gene rearrangement (ALK[+]), which is sensitive to dual ALK and MET inhibitor Crizotinib, has not been reported.	Crizotinib	146-156	ALK receptor tyrosine kinase	Homo sapiens	88-91
24722154-3	2014	However, the deregulation of MET/HGF pathway in NSCLC harboring ALK gene rearrangement (ALK[+]), which is sensitive to dual ALK and MET inhibitor Crizotinib, has not been reported.	Crizotinib	146-156	ALK receptor tyrosine kinase	Homo sapiens	88-91
24598368-0	2014	Overcoming the resistance to crizotinib in patients with non-small cell lung cancer harboring EML4/ALK translocation.	Crizotinib	29-39	EMAP like 4	Homo sapiens	94-98
24598368-0	2014	Overcoming the resistance to crizotinib in patients with non-small cell lung cancer harboring EML4/ALK translocation.	Crizotinib	29-39	ALK receptor tyrosine kinase	Homo sapiens	99-102
24598368-4	2014	In 2011, regulatory entities granted conditional approval to an anaplastic lymphoma kinase inhibitor (crizotinib) based on an impressive overall response rate in previously treated non-small cell lung cancer patients whose tumors harbored EML4/ALK translocations.	Crizotinib	102-112	EMAP like 4	Homo sapiens	239-243
24598368-4	2014	In 2011, regulatory entities granted conditional approval to an anaplastic lymphoma kinase inhibitor (crizotinib) based on an impressive overall response rate in previously treated non-small cell lung cancer patients whose tumors harbored EML4/ALK translocations.	Crizotinib	102-112	ALK receptor tyrosine kinase	Homo sapiens	244-247
24573551-0	2014	U.S. Food and Drug Administration approval: crizotinib for treatment of advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase positive.	Crizotinib	44-54	ALK receptor tyrosine kinase	Homo sapiens	130-156
24573551-1	2014	On August 26, 2011, the U.S. Food and Drug Administration (FDA) approved crizotinib (XALKORI Capsules, Pfizer Inc.) for treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive as detected by an FDA-approved test.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	221-247
24573551-1	2014	On August 26, 2011, the U.S. Food and Drug Administration (FDA) approved crizotinib (XALKORI Capsules, Pfizer Inc.) for treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive as detected by an FDA-approved test.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	86-89
24573551-8	2014	On November 20, 2013, crizotinib received full approval based on an improvement in progression-free survival in patients with metastatic ALK-positive NSCLC previously treated with one platinum-based chemotherapy regimen.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	137-140
24695225-5	2014	Searching for more drug-like inhibitors, we identified the kinase inhibitor crizotinib as a nanomolar suppressor of MTH1 activity.	Crizotinib	76-86	nudix hydrolase 1	Homo sapiens	116-120
24695225-8	2014	Disruption of nucleotide pool homeostasis via MTH1 inhibition by (S)-crizotinib induced an increase in DNA single-strand breaks, activated DNA repair in human colon carcinoma cells, and effectively suppressed tumour growth in animal models.	Crizotinib	65-79	nudix hydrolase 1	Homo sapiens	46-50
25988009-0	2014	Acute interstitial lung disease in a patient with anaplastic lymphoma kinase-positive non-small-cell lung cancer after crizotinib therapy.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	50-76
25988009-1	2014	Crizotinib, an orally active multi-targeted small-molecule anaplastic lymphoma kinase (ALK) inhibitor, is an effective treatment modality for advanced ALK-positive non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	59-85
25988009-1	2014	Crizotinib, an orally active multi-targeted small-molecule anaplastic lymphoma kinase (ALK) inhibitor, is an effective treatment modality for advanced ALK-positive non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	87-90
25988009-1	2014	Crizotinib, an orally active multi-targeted small-molecule anaplastic lymphoma kinase (ALK) inhibitor, is an effective treatment modality for advanced ALK-positive non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	151-154
24476492-9	2014	The focus of ALK research appears to have shifted toward inhibitors that display activity against resistant mutants unearthed in clinical studies with crizotinib.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	13-16
24744988-1	2014	The discovery of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC) in 2007 and the approval of crizotinib for the treatment of advanced ALK-rearranged NSCLC in 2011 represents a landmark in the development of targeted oncology therapy.	Crizotinib	130-140	ALK receptor tyrosine kinase	Homo sapiens	171-174
24744988-3	2014	Pfizer, the manufacturer of crizotinib, sponsored the screening of thousands of patients and the standardization of the ALK FISH test as part of the approval process for crizotinib, a first in class ALK inhibitor.	Crizotinib	170-180	ALK receptor tyrosine kinase	Homo sapiens	199-202
24744988-7	2014	Crizotinib has now demonstrated significant clinical activity in ROS1-rearranged NSCLC patients.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	65-69
24744988-10	2014	Given the low incidence of ROS1-rearrangement in NSCLC, and the availability of crizotinib in most countries, a more cost-effective way is for crizotinib to gain compendium listing for ROS1-rearranged NSCLC in treatment guidelines.	Crizotinib	143-153	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	27-31
24955213-3	2014	The tyrosine kinase inhibitor crizotinib is more effective than standard chemotherapeutic agents in treating ALK positive NSCLC, making molecular diagnostic testing for dysregulated ALK expression a necessary step in identifying optimal treatment modalities.	Crizotinib	30-40	ALK receptor tyrosine kinase	Homo sapiens	109-112
24955213-3	2014	The tyrosine kinase inhibitor crizotinib is more effective than standard chemotherapeutic agents in treating ALK positive NSCLC, making molecular diagnostic testing for dysregulated ALK expression a necessary step in identifying optimal treatment modalities.	Crizotinib	30-40	ALK receptor tyrosine kinase	Homo sapiens	182-185
24509625-1	2014	PURPOSE: Crizotinib, the first FDA-approved ALK inhibitor, showed significant antitumor activity in young patients with anaplastic large-cell lymphoma (ALCL) frequently displaying ALK rearrangement.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	44-47
24744988-10	2014	Given the low incidence of ROS1-rearrangement in NSCLC, and the availability of crizotinib in most countries, a more cost-effective way is for crizotinib to gain compendium listing for ROS1-rearranged NSCLC in treatment guidelines.	Crizotinib	143-153	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	185-189
24509625-1	2014	PURPOSE: Crizotinib, the first FDA-approved ALK inhibitor, showed significant antitumor activity in young patients with anaplastic large-cell lymphoma (ALCL) frequently displaying ALK rearrangement.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	180-183
24509625-3	2014	CH5424802--more potent and selective ALK inhibitor--comprises a good candidate for second-line treatment in crizotinib-relapsed patients.	Crizotinib	108-118	ALK receptor tyrosine kinase	Homo sapiens	37-40
24509625-5	2014	METHODS: ALK+ ALCL cell lines resistant to crizotinib (Karpas299CR) and to CH5424802 (Karpas299CHR) were established by long-term exposure of Karpas299 cells to these inhibitors.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	9-12
24509625-8	2014	The resistant cells displayed diminished sensitivity to structurally unrelated ALK inhibitors-crizotinib, CH5424802 and TAE684.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	79-82
24567430-1	2014	PURPOSE: ALK-targeted therapy with crizotinib offers significant improvement in clinical outcomes for the treatment of EML4-ALK fusion-positive non-small-cell lung cancer (NSCLC).	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	9-12
24567430-1	2014	PURPOSE: ALK-targeted therapy with crizotinib offers significant improvement in clinical outcomes for the treatment of EML4-ALK fusion-positive non-small-cell lung cancer (NSCLC).	Crizotinib	35-45	EMAP like 4	Homo sapiens	119-123
24567430-1	2014	PURPOSE: ALK-targeted therapy with crizotinib offers significant improvement in clinical outcomes for the treatment of EML4-ALK fusion-positive non-small-cell lung cancer (NSCLC).	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	124-127
24736067-1	2014	INTRODUCTION: Oncogenic anaplastic lymphoma kinase (ALK) gene rearrangements in non-small-cell lung carcinomas (NSCLC) provide the basis for targeted therapy with crizotinib and other specific ALK inhibitors.	Crizotinib	163-173	ALK receptor tyrosine kinase	Homo sapiens	52-55
24736079-1	2014	Acquired secondary mutations in the anaplastic lymphoma kinase (ALK) gene have been identified in ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC) patients who developed disease progression while on crizotinib treatment.	Crizotinib	207-217	ALK receptor tyrosine kinase	Homo sapiens	36-62
24736079-1	2014	Acquired secondary mutations in the anaplastic lymphoma kinase (ALK) gene have been identified in ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC) patients who developed disease progression while on crizotinib treatment.	Crizotinib	207-217	ALK receptor tyrosine kinase	Homo sapiens	64-67
24736079-1	2014	Acquired secondary mutations in the anaplastic lymphoma kinase (ALK) gene have been identified in ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC) patients who developed disease progression while on crizotinib treatment.	Crizotinib	207-217	ALK receptor tyrosine kinase	Homo sapiens	98-101
24736079-1	2014	Acquired secondary mutations in the anaplastic lymphoma kinase (ALK) gene have been identified in ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC) patients who developed disease progression while on crizotinib treatment.	Crizotinib	207-217	ALK receptor tyrosine kinase	Homo sapiens	98-101
24736079-2	2014	Here, we identified a novel secondary acquired NSCLC ALK F1174V mutation by comprehensive next-generation sequencing in one ALK+ NSCLC patient who progressed on crizotinib after a prolonged partial response to crizotinib.	Crizotinib	161-171	ALK receptor tyrosine kinase	Homo sapiens	53-56
24736079-2	2014	Here, we identified a novel secondary acquired NSCLC ALK F1174V mutation by comprehensive next-generation sequencing in one ALK+ NSCLC patient who progressed on crizotinib after a prolonged partial response to crizotinib.	Crizotinib	161-171	ALK receptor tyrosine kinase	Homo sapiens	124-127
24736079-2	2014	Here, we identified a novel secondary acquired NSCLC ALK F1174V mutation by comprehensive next-generation sequencing in one ALK+ NSCLC patient who progressed on crizotinib after a prolonged partial response to crizotinib.	Crizotinib	210-220	ALK receptor tyrosine kinase	Homo sapiens	53-56
24736079-2	2014	Here, we identified a novel secondary acquired NSCLC ALK F1174V mutation by comprehensive next-generation sequencing in one ALK+ NSCLC patient who progressed on crizotinib after a prolonged partial response to crizotinib.	Crizotinib	210-220	ALK receptor tyrosine kinase	Homo sapiens	124-127
24736079-5	2014	Comprehensive genomic profiling of resistant tumor is increasingly important in tailoring treatment decisions after disease progression on crizotinib in ALK+ NSCLC given the promise of second-generation ALK inhibitors and other therapeutic strategies.	Crizotinib	139-149	ALK receptor tyrosine kinase	Homo sapiens	153-156
24486291-0	2014	Crizotinib (PF-2341066) induces apoptosis due to downregulation of pSTAT3 and BCL-2 family proteins in NPM-ALK(+) anaplastic large cell lymphoma.	Crizotinib	0-10	BCL2 apoptosis regulator	Homo sapiens	78-83
24486291-0	2014	Crizotinib (PF-2341066) induces apoptosis due to downregulation of pSTAT3 and BCL-2 family proteins in NPM-ALK(+) anaplastic large cell lymphoma.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	107-110
24486291-5	2014	Crizotinib (PF-2341066) is a small, orally bioavailable molecule that inhibits growth of tumors with ALK activity as shown in a subgroup of non-small lung cancer patients with EML4-ALK expression.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	101-104
24486291-5	2014	Crizotinib (PF-2341066) is a small, orally bioavailable molecule that inhibits growth of tumors with ALK activity as shown in a subgroup of non-small lung cancer patients with EML4-ALK expression.	Crizotinib	0-10	EMAP like 4	Homo sapiens	176-180
24486291-5	2014	Crizotinib (PF-2341066) is a small, orally bioavailable molecule that inhibits growth of tumors with ALK activity as shown in a subgroup of non-small lung cancer patients with EML4-ALK expression.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	181-184
24486291-6	2014	In this study, we have investigated the in vitro effects of Crizotinib in ALCL cell line with NPM-ALK fusion.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	98-101
24486291-7	2014	Crizotinib induced marked downregulation of STAT3 phosphorylation, which was associated with significant apoptotic cell death.	Crizotinib	0-10	signal transducer and activator of transcription 3	Homo sapiens	44-49
24486291-9	2014	These findings implicate that Crizotinib has excellent potential to treat patients with NPM-ALK(+) ALCL through induction of apoptotic cell death and downregulation of major oncogenic proteins in this aggressive lymphoma.	Crizotinib	30-40	ALK receptor tyrosine kinase	Homo sapiens	92-95
25022069-5	2014	The Vysis ALK Break Apart FISH Probe Kit is a test to detect rearrangements involving the ALK gene in tissue samples from non-small cell lung cancer (NSCLC) patients to aid in identifying patients eligible for treatment with Crizotinib.	Crizotinib	225-235	ALK receptor tyrosine kinase	Homo sapiens	10-13
25022069-5	2014	The Vysis ALK Break Apart FISH Probe Kit is a test to detect rearrangements involving the ALK gene in tissue samples from non-small cell lung cancer (NSCLC) patients to aid in identifying patients eligible for treatment with Crizotinib.	Crizotinib	225-235	ALK receptor tyrosine kinase	Homo sapiens	90-93
24670165-1	2014	BACKGROUND: Non-small-cell lung cancer (NSCLC) harboring the anaplastic lymphoma kinase gene (ALK) rearrangement is sensitive to the ALK inhibitor crizotinib, but resistance invariably develops.	Crizotinib	147-157	ALK receptor tyrosine kinase	Homo sapiens	94-97
24567430-8	2014	Among patients with known EML4-ALK-positive advanced NSCLC, first-line crizotinib therapy provided 0.379 additional QALYs, cost an additional $95,043 compared with standard care, and produced an ICER of $250,632 per QALY gained.	Crizotinib	71-81	EMAP like 4	Homo sapiens	26-30
24567430-8	2014	Among patients with known EML4-ALK-positive advanced NSCLC, first-line crizotinib therapy provided 0.379 additional QALYs, cost an additional $95,043 compared with standard care, and produced an ICER of $250,632 per QALY gained.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	31-34
24567430-10	2014	CONCLUSION: EML4-ALK fusion testing in stage IV nonsquamous NSCLC with crizotinib treatment for ALK-positive patients is not cost effective in the setting of high drug costs and a low biomarker frequency in the population.	Crizotinib	71-81	EMAP like 4	Homo sapiens	12-16
24567430-10	2014	CONCLUSION: EML4-ALK fusion testing in stage IV nonsquamous NSCLC with crizotinib treatment for ALK-positive patients is not cost effective in the setting of high drug costs and a low biomarker frequency in the population.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	17-20
24567430-10	2014	CONCLUSION: EML4-ALK fusion testing in stage IV nonsquamous NSCLC with crizotinib treatment for ALK-positive patients is not cost effective in the setting of high drug costs and a low biomarker frequency in the population.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	96-99
24613930-7	2014	The kinase activity of STRN-ALK and the ALK-induced cell growth can be blocked by the ALK inhibitors crizotinib and TAE684.	Crizotinib	101-111	striatin	Homo sapiens	23-27
24613930-7	2014	The kinase activity of STRN-ALK and the ALK-induced cell growth can be blocked by the ALK inhibitors crizotinib and TAE684.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	28-31
24613930-7	2014	The kinase activity of STRN-ALK and the ALK-induced cell growth can be blocked by the ALK inhibitors crizotinib and TAE684.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	40-43
24613930-7	2014	The kinase activity of STRN-ALK and the ALK-induced cell growth can be blocked by the ALK inhibitors crizotinib and TAE684.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	40-43
24037730-0	2014	Increased oral availability and brain accumulation of the ALK inhibitor crizotinib by coadministration of the P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) inhibitor elacridar.	Crizotinib	72-82	anaplastic lymphoma kinase	Mus musculus	58-61
24037730-0	2014	Increased oral availability and brain accumulation of the ALK inhibitor crizotinib by coadministration of the P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) inhibitor elacridar.	Crizotinib	72-82	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	126-131
24037730-0	2014	Increased oral availability and brain accumulation of the ALK inhibitor crizotinib by coadministration of the P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) inhibitor elacridar.	Crizotinib	72-82	ATP binding cassette subfamily G member 2 (Junior blood group)	Mus musculus	171-176
24623980-3	2014	A small-molecule tyrosine-kinase inhibitor of ALK, crizotinib, was rapidly approved by the US Food and Drug Administration on the basis of its pronounced clinical activity in patients with ALK rearrangement-positive NSCLC.	Crizotinib	51-61	ALK receptor tyrosine kinase	Homo sapiens	46-49
24623980-3	2014	A small-molecule tyrosine-kinase inhibitor of ALK, crizotinib, was rapidly approved by the US Food and Drug Administration on the basis of its pronounced clinical activity in patients with ALK rearrangement-positive NSCLC.	Crizotinib	51-61	ALK receptor tyrosine kinase	Homo sapiens	189-192
24258622-0	2014	Drug-induced reduction in estimated glomerular filtration rate in patients with ALK-positive non-small cell lung cancer treated with the ALK inhibitor crizotinib.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	80-83
24258622-0	2014	Drug-induced reduction in estimated glomerular filtration rate in patients with ALK-positive non-small cell lung cancer treated with the ALK inhibitor crizotinib.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	137-140
24258622-3	2014	RESULTS: A total of 38 patients with stage IV anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer who were treated with crizotinib were identified.	Crizotinib	137-147	ALK receptor tyrosine kinase	Homo sapiens	74-77
24327273-0	2014	Co-clinical trials demonstrate superiority of crizotinib to chemotherapy in ALK-rearranged non-small cell lung cancer and predict strategies to overcome resistance.	Crizotinib	46-56	anaplastic lymphoma kinase	Mus musculus	76-79
24327273-2	2014	EXPERIMENTAL DESIGN: We conducted a co-clinical trial in a mouse model comparing the ALK inhibitor crizotinib to the standard-of-care cytotoxic agents docetaxel or pemetrexed.	Crizotinib	99-109	anaplastic lymphoma kinase	Mus musculus	85-88
24443522-0	2014	Lung cancers with concomitant EGFR mutations and ALK rearrangements: diverse responses to EGFR-TKI and crizotinib in relation to diverse receptors phosphorylation.	Crizotinib	103-113	epidermal growth factor receptor	Homo sapiens	30-34
24443522-0	2014	Lung cancers with concomitant EGFR mutations and ALK rearrangements: diverse responses to EGFR-TKI and crizotinib in relation to diverse receptors phosphorylation.	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	49-52
24443522-3	2014	Immunohistochemistry (IHC) and Western blotting were used to correlate the activation of EGFR, ALK, and downstream proteins with responses to EGFR-TKIs and crizotinib.	Crizotinib	156-166	epidermal growth factor receptor	Homo sapiens	89-93
24443522-10	2014	Two cases with high phospho-ALK levels treated with crizotinib achieved partial responses; two cases with low phospho-ALK levels had progressive or stable disease.	Crizotinib	52-62	ALK receptor tyrosine kinase	Homo sapiens	28-31
24443522-13	2014	Relative phospho-ALK and phospho-EGFR levels could predict the efficacy of EGFR-TKI and crizotinib.	Crizotinib	88-98	ALK receptor tyrosine kinase	Homo sapiens	17-20
24443522-13	2014	Relative phospho-ALK and phospho-EGFR levels could predict the efficacy of EGFR-TKI and crizotinib.	Crizotinib	88-98	epidermal growth factor receptor	Homo sapiens	33-37
24616538-5	2014	This article describes a patient with refractory ALK(+) anaplastic large cell lymphoma who experienced a complete response to the ALK inhibitor crizotinib and then underwent an allogeneic stem cell transplant followed by crizotinib maintenance therapy.	Crizotinib	144-154	ALK receptor tyrosine kinase	Homo sapiens	49-52
24616538-5	2014	This article describes a patient with refractory ALK(+) anaplastic large cell lymphoma who experienced a complete response to the ALK inhibitor crizotinib and then underwent an allogeneic stem cell transplant followed by crizotinib maintenance therapy.	Crizotinib	144-154	ALK receptor tyrosine kinase	Homo sapiens	130-133
24616538-5	2014	This article describes a patient with refractory ALK(+) anaplastic large cell lymphoma who experienced a complete response to the ALK inhibitor crizotinib and then underwent an allogeneic stem cell transplant followed by crizotinib maintenance therapy.	Crizotinib	221-231	ALK receptor tyrosine kinase	Homo sapiens	49-52
24616538-5	2014	This article describes a patient with refractory ALK(+) anaplastic large cell lymphoma who experienced a complete response to the ALK inhibitor crizotinib and then underwent an allogeneic stem cell transplant followed by crizotinib maintenance therapy.	Crizotinib	221-231	ALK receptor tyrosine kinase	Homo sapiens	130-133
24496003-11	2014	In addition, the HIP1-ALK-rearranged tumor is sensitive to treatment with crizotinib in vivo, implicating HIP1-ALKas an oncogenic driver of lung tumorigenesis.	Crizotinib	74-84	huntingtin interacting protein 1	Homo sapiens	106-110
24496003-12	2014	Collectively, our results indicate that HIP1-ALK-positive NSCLC may benefit from clinical applications of crizotinib.	Crizotinib	106-116	huntingtin interacting protein 1	Homo sapiens	40-44
24496003-12	2014	Collectively, our results indicate that HIP1-ALK-positive NSCLC may benefit from clinical applications of crizotinib.	Crizotinib	106-116	ALK receptor tyrosine kinase	Homo sapiens	45-48
24518086-2	2014	Crizotinib, an ALK inhibitor, has been demonstrated to provide dramatic clinical benefits in ALK-positive advanced-stage NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	15-18
24518086-2	2014	Crizotinib, an ALK inhibitor, has been demonstrated to provide dramatic clinical benefits in ALK-positive advanced-stage NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	93-96
24518086-13	2014	This significant level of discrepancy supports the need of combined testing to optimize the detection of ALK-inhibitor-eligible patients given that some patients with discordant testing were found to respond to crizotinib.	Crizotinib	211-221	ALK receptor tyrosine kinase	Homo sapiens	105-108
24712007-5	2014	mTOR inhibitors are active in PEComas (perivascular epitheloid cell tumors) and crizotinib in ALK rearranged inflammatory myofibroblastic tumors.	Crizotinib	80-90	ALK receptor tyrosine kinase	Homo sapiens	94-97
24498900-2	2014	is an excellent example of rational structure-based and lipophilic-efficiency optimization of crizotinib (Xalkori) aimed at novel ALK inhibitors capable of overcoming clinically acquired resistance against the current drug in NSCLC patients.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	130-133
24468632-4	2014	The inhibition of ALK was evaluated and compound 19 in particular showed good activity against both the wild type and crizotinib-resistant L1196M mutant in vitro and in ALK-transfected BaF3 cells.	Crizotinib	118-128	anaplastic lymphoma kinase	Mus musculus	18-21
24478318-0	2014	Clinical benefit of continuing ALK inhibition with crizotinib beyond initial disease progression in patients with advanced ALK-positive NSCLC.	Crizotinib	51-61	ALK receptor tyrosine kinase	Homo sapiens	31-34
24305878-4	2014	LY2801653 was more efficacious than the MET/ALK/RON/ROS inhibitor crizotinib with a distinct pattern of downstream signaling effects.	Crizotinib	66-76	anaplastic lymphoma kinase	Mus musculus	44-47
24305878-4	2014	LY2801653 was more efficacious than the MET/ALK/RON/ROS inhibitor crizotinib with a distinct pattern of downstream signaling effects.	Crizotinib	66-76	macrophage stimulating 1 receptor (c-met-related tyrosine kinase)	Mus musculus	48-51
24355409-5	2014	Following the development of small molecules (gefitinib/erlotinib and crizotinib) able to reversibly inhibit the epidermal growth factor receptor (EGFR) and signaling pathways mediated by anaplastic lymphoma kinase (ALK), respectively, the MET signaling pathway has also been recognized as a potential target.	Crizotinib	70-80	epidermal growth factor receptor	Homo sapiens	113-145
24355409-5	2014	Following the development of small molecules (gefitinib/erlotinib and crizotinib) able to reversibly inhibit the epidermal growth factor receptor (EGFR) and signaling pathways mediated by anaplastic lymphoma kinase (ALK), respectively, the MET signaling pathway has also been recognized as a potential target.	Crizotinib	70-80	epidermal growth factor receptor	Homo sapiens	147-151
24355409-5	2014	Following the development of small molecules (gefitinib/erlotinib and crizotinib) able to reversibly inhibit the epidermal growth factor receptor (EGFR) and signaling pathways mediated by anaplastic lymphoma kinase (ALK), respectively, the MET signaling pathway has also been recognized as a potential target.	Crizotinib	70-80	ALK receptor tyrosine kinase	Homo sapiens	188-214
24355409-5	2014	Following the development of small molecules (gefitinib/erlotinib and crizotinib) able to reversibly inhibit the epidermal growth factor receptor (EGFR) and signaling pathways mediated by anaplastic lymphoma kinase (ALK), respectively, the MET signaling pathway has also been recognized as a potential target.	Crizotinib	70-80	ALK receptor tyrosine kinase	Homo sapiens	216-219
24490607-0	2014	Crizotinib inhibits migration and expression of ID1 in MET-positive lung cancer cells: implications for MET targeting in oncology.	Crizotinib	0-10	inhibitor of DNA binding 1, HLH protein	Homo sapiens	48-51
24490607-2	2014	We hypothesized that the ALK/MET inhibitor crizotinib inhibits migration via MET-SRC-ID1, rather than ALK.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	25-28
24490607-2	2014	We hypothesized that the ALK/MET inhibitor crizotinib inhibits migration via MET-SRC-ID1, rather than ALK.	Crizotinib	43-53	SRC proto-oncogene, non-receptor tyrosine kinase	Homo sapiens	81-84
24490607-2	2014	We hypothesized that the ALK/MET inhibitor crizotinib inhibits migration via MET-SRC-ID1, rather than ALK.	Crizotinib	43-53	inhibitor of DNA binding 1, HLH protein	Homo sapiens	85-88
24490607-5	2014	RESULTS: Crizotinib decreased p-MET, p-SRC and ID1 levels in ALK- and or MET-positive cell lines and inhibited cell migration.	Crizotinib	9-19	SRC proto-oncogene, non-receptor tyrosine kinase	Homo sapiens	39-42
24490607-5	2014	RESULTS: Crizotinib decreased p-MET, p-SRC and ID1 levels in ALK- and or MET-positive cell lines and inhibited cell migration.	Crizotinib	9-19	inhibitor of DNA binding 1, HLH protein	Homo sapiens	47-50
24490607-5	2014	RESULTS: Crizotinib decreased p-MET, p-SRC and ID1 levels in ALK- and or MET-positive cell lines and inhibited cell migration.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	61-64
24490607-7	2014	CONCLUSION: The effects of crizotinib on ID1 expression and cancer cell migration were associated with the presence of activated MET, rather than ALK fusion.	Crizotinib	27-37	inhibitor of DNA binding 1, HLH protein	Homo sapiens	41-44
24490615-4	2014	New drugs specifically dedicated for ALK inhibition, for example, crizotinib, have been synthesized and have become a viable treatment option for ALK-positive lung adenocarcinoma, and potentially for other ALK-positive cancers.	Crizotinib	66-76	ALK receptor tyrosine kinase	Homo sapiens	37-40
24490615-4	2014	New drugs specifically dedicated for ALK inhibition, for example, crizotinib, have been synthesized and have become a viable treatment option for ALK-positive lung adenocarcinoma, and potentially for other ALK-positive cancers.	Crizotinib	66-76	ALK receptor tyrosine kinase	Homo sapiens	146-149
24490615-4	2014	New drugs specifically dedicated for ALK inhibition, for example, crizotinib, have been synthesized and have become a viable treatment option for ALK-positive lung adenocarcinoma, and potentially for other ALK-positive cancers.	Crizotinib	66-76	ALK receptor tyrosine kinase	Homo sapiens	146-149
24667968-1	2014	The early identification of children presenting ALK(F1174L)-mutated neuroblastoma, which are associated with resistance to the promising ALK inhibitor crizotinib and a marked poorer prognosis, has become a clinical priority.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	48-51
24667968-1	2014	The early identification of children presenting ALK(F1174L)-mutated neuroblastoma, which are associated with resistance to the promising ALK inhibitor crizotinib and a marked poorer prognosis, has become a clinical priority.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	137-140
24419120-0	2014	Long-term response to gefitinib and crizotinib in lung adenocarcinoma harboring both epidermal growth factor receptor mutation and EML4-ALK fusion gene.	Crizotinib	36-46	epidermal growth factor receptor	Homo sapiens	85-117
24419120-0	2014	Long-term response to gefitinib and crizotinib in lung adenocarcinoma harboring both epidermal growth factor receptor mutation and EML4-ALK fusion gene.	Crizotinib	36-46	EMAP like 4	Homo sapiens	131-135
24419120-0	2014	Long-term response to gefitinib and crizotinib in lung adenocarcinoma harboring both epidermal growth factor receptor mutation and EML4-ALK fusion gene.	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	136-139
24715763-0	2014	ALK-driven tumors and targeted therapy: focus on crizotinib.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	0-3
24037730-1	2014	Crizotinib is an oral tyrosine kinase inhibitor approved for treating patients with non-small cell lung cancer (NSCLC) containing an anaplastic lymphoma kinase (ALK) rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	133-159
24037730-1	2014	Crizotinib is an oral tyrosine kinase inhibitor approved for treating patients with non-small cell lung cancer (NSCLC) containing an anaplastic lymphoma kinase (ALK) rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	161-164
24037730-2	2014	We used knockout mice to study the roles of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) in plasma pharmacokinetics and brain accumulation of oral crizotinib, and the feasibility of improving crizotinib kinetics using coadministration of the dual ABCB1/ABCG2 inhibitor elacridar.	Crizotinib	170-180	ATP binding cassette subfamily G member 2 (Junior blood group)	Mus musculus	105-110
24037730-3	2014	In vitro, crizotinib was a good transport substrate of human ABCB1, but not of human ABCG2 or murine Abcg2.	Crizotinib	10-20	ATP binding cassette subfamily B member 1	Homo sapiens	61-66
24037730-4	2014	With low-dose oral crizotinib (5 mg/kg), Abcb1a/1b(-/-) and Abcb1a/1b;Abcg2(-/-) mice had an approximately twofold higher plasma AUC than wild-type mice, and a markedly (~40-fold) higher brain accumulation at 24 hr.	Crizotinib	19-29	ATP-binding cassette, sub-family B (MDR/TAP), member 1A	Mus musculus	41-47
24037730-9	2014	Our results indicate that crizotinib oral availability and brain accumulation were primarily restricted by Abcb1 at a non-saturating dose, and that coadministration of elacridar with crizotinib could substantially increase crizotinib oral availability and delivery to the brain.	Crizotinib	26-36	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	107-112
23931927-8	2014	Crizotinib, a first-in-class dual ALK and c-MET inhibitor, has been shown to be particularly effective against ALK positive NSCLC, showing dramatic and prolonged responses with low toxicity, predominantly restricted to the gastro-intestinal and visual systems, and generally self-limiting or easily managed.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	34-37
23931927-8	2014	Crizotinib, a first-in-class dual ALK and c-MET inhibitor, has been shown to be particularly effective against ALK positive NSCLC, showing dramatic and prolonged responses with low toxicity, predominantly restricted to the gastro-intestinal and visual systems, and generally self-limiting or easily managed.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	42-47
23931927-8	2014	Crizotinib, a first-in-class dual ALK and c-MET inhibitor, has been shown to be particularly effective against ALK positive NSCLC, showing dramatic and prolonged responses with low toxicity, predominantly restricted to the gastro-intestinal and visual systems, and generally self-limiting or easily managed.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	111-114
24327273-6	2014	In addition, in the EML4-ALK-driven mouse lung adenocarcinoma model, HSP90 inhibition can overcome both primary and acquired crizotinib resistance.	Crizotinib	125-135	echinoderm microtubule associated protein like 4	Mus musculus	20-24
24327273-6	2014	In addition, in the EML4-ALK-driven mouse lung adenocarcinoma model, HSP90 inhibition can overcome both primary and acquired crizotinib resistance.	Crizotinib	125-135	anaplastic lymphoma kinase	Mus musculus	25-28
24327273-6	2014	In addition, in the EML4-ALK-driven mouse lung adenocarcinoma model, HSP90 inhibition can overcome both primary and acquired crizotinib resistance.	Crizotinib	125-135	heat shock protein 86, pseudogene 1	Mus musculus	69-74
24327273-7	2014	Furthermore, HSP90 inhibition, as well as the second-generation ALK inhibitor TAE684, demonstrated activity in newly developed lung adenocarcinoma models driven by crizotinib-insensitive EML4-ALK L1196M or F1174L.	Crizotinib	164-174	heat shock protein 86, pseudogene 1	Mus musculus	13-18
24327273-8	2014	CONCLUSIONS: Our findings suggest that crizotinib is superior to standard chemotherapy in ALK inhibitor-naive disease and support further clinical investigation of HSP90 inhibitors and second-generation ALK inhibitors in tumors with primary or acquired crizotinib resistance.	Crizotinib	39-49	anaplastic lymphoma kinase	Mus musculus	90-93
24156959-2	2014	The striking results from clinical trials with crizotinib, the first ALK inhibitor evaluated, allowed the accelerated approval of crizotinib from the USA Food and Drug Administration (FDA).	Crizotinib	47-57	ALK receptor tyrosine kinase	Homo sapiens	69-72
24156959-2	2014	The striking results from clinical trials with crizotinib, the first ALK inhibitor evaluated, allowed the accelerated approval of crizotinib from the USA Food and Drug Administration (FDA).	Crizotinib	130-140	ALK receptor tyrosine kinase	Homo sapiens	69-72
24418728-2	2014	Although tumors harboring ALK fusions are highly sensitive to crizotinib, emerging preclinical and clinical data demonstrate that patients with ROS1 or RET fusions may also benefit from inhibitors targeting these kinases.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	26-29
24496003-0	2014	HIP1-ALK, a novel ALK fusion variant that responds to crizotinib.	Crizotinib	54-64	huntingtin interacting protein 1	Homo sapiens	0-4
24496003-0	2014	HIP1-ALK, a novel ALK fusion variant that responds to crizotinib.	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	5-8
24496003-0	2014	HIP1-ALK, a novel ALK fusion variant that responds to crizotinib.	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	18-21
24496003-1	2014	INTRODUCTION: The aim of this study was to identify anaplastic lymphoma kinase (ALK) rearrangements in lung cancer patient-derived xenograft (PDX) models and to explore their responses to crizotinib.	Crizotinib	188-198	ALK receptor tyrosine kinase	Homo sapiens	52-78
24496003-1	2014	INTRODUCTION: The aim of this study was to identify anaplastic lymphoma kinase (ALK) rearrangements in lung cancer patient-derived xenograft (PDX) models and to explore their responses to crizotinib.	Crizotinib	188-198	ALK receptor tyrosine kinase	Homo sapiens	80-83
24496003-4	2014	Finally, pharmacological studies were performed in PDX models to evaluate their responses to ALK inhibitor crizotinib.	Crizotinib	107-117	ALK receptor tyrosine kinase	Homo sapiens	93-96
24496003-9	2014	Furthermore, in vivo efficacy studies demonstrated that, similar to the EML4-ALK-positive model, the HIP1-ALK-containing PDX model was sensitive to treatment with crizotinib.	Crizotinib	163-173	huntingtin interacting protein 1	Homo sapiens	101-105
24496003-9	2014	Furthermore, in vivo efficacy studies demonstrated that, similar to the EML4-ALK-positive model, the HIP1-ALK-containing PDX model was sensitive to treatment with crizotinib.	Crizotinib	163-173	ALK receptor tyrosine kinase	Homo sapiens	106-109
24496003-11	2014	In addition, the HIP1-ALK-rearranged tumor is sensitive to treatment with crizotinib in vivo, implicating HIP1-ALKas an oncogenic driver of lung tumorigenesis.	Crizotinib	74-84	huntingtin interacting protein 1	Homo sapiens	17-21
24496003-11	2014	In addition, the HIP1-ALK-rearranged tumor is sensitive to treatment with crizotinib in vivo, implicating HIP1-ALKas an oncogenic driver of lung tumorigenesis.	Crizotinib	74-84	ALK receptor tyrosine kinase	Homo sapiens	22-25
24432909-0	2014	Design of potent and selective inhibitors to overcome clinical anaplastic lymphoma kinase mutations resistant to crizotinib.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	63-89
24432909-1	2014	Crizotinib (1), an anaplastic lymphoma kinase (ALK) receptor tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration in 2011, is efficacious in ALK and ROS positive patients.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	19-45
24432909-1	2014	Crizotinib (1), an anaplastic lymphoma kinase (ALK) receptor tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration in 2011, is efficacious in ALK and ROS positive patients.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	47-50
24432909-1	2014	Crizotinib (1), an anaplastic lymphoma kinase (ALK) receptor tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration in 2011, is efficacious in ALK and ROS positive patients.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	164-167
24432909-2	2014	Under pressure of crizotinib treatment, point mutations arise in the kinase domain of ALK, resulting in resistance and progressive disease.	Crizotinib	18-28	ALK receptor tyrosine kinase	Homo sapiens	86-89
24284055-3	2014	EXPERIMENTAL DESIGN: SCLC models of HGF-induced EMT were evaluated in vitro and in vivo (subcutaneous xenografts in BALB/c nude mice) for chemosensitivity and response to Met inhibition with PF-2341066 (crizotinib).	Crizotinib	203-213	hepatocyte growth factor	Mus musculus	36-39
24478318-1	2014	BACKGROUND: Crizotinib is approved to treat advanced ALK-positive non-small-cell lung cancer (NSCLC), but most patients ultimately develop progressive disease (PD).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	53-56
24478318-2	2014	We investigated whether continuing ALK inhibition with crizotinib beyond PD (CBPD) is clinically beneficial and attempted to identify clinicopathologic characteristics associated with patients who experience clinical benefit.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	35-38
24478318-13	2014	Continuing ALK inhibition with crizotinib after PD may provide survival benefit to patients with advanced ALK-positive NSCLC.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	11-14
24478318-13	2014	Continuing ALK inhibition with crizotinib after PD may provide survival benefit to patients with advanced ALK-positive NSCLC.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	106-109
24403104-12	2014	ALK-positive patients have a good response to first-line cytotoxic drugs and to crizotinib as second-line therapy, but a relatively poor response to cytotoxic drugs as second-line therapy.	Crizotinib	80-90	ALK receptor tyrosine kinase	Homo sapiens	0-3
24523601-2	2014	Small-molecule Alk kinase inhibitors such as crizotinib have transformed the natural history of nsclc for this subgroup of patients.	Crizotinib	45-55	ALK receptor tyrosine kinase	Homo sapiens	15-18
24523601-4	2014	Although Alk inhibitors such as crizotinib are well tolerated, there is a potential for adverse events to occur.	Crizotinib	32-42	ALK receptor tyrosine kinase	Homo sapiens	9-12
24523601-6	2014	The present review summarizes the management of treatment-related adverse events that can arise with Alk inhibitors such as crizotinib.	Crizotinib	124-134	ALK receptor tyrosine kinase	Homo sapiens	101-104
24491302-0	2014	Crizotinib in advanced, chemoresistant anaplastic lymphoma kinase-positive lymphoma patients.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	39-65
24491302-2	2014	Crizotinib inhibits ALK in vitro and in vivo and was administered as monotherapy to 11 ALK+ lymphoma patients who were resistant/refractory to cytotoxic therapy.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	20-23
24491302-2	2014	Crizotinib inhibits ALK in vitro and in vivo and was administered as monotherapy to 11 ALK+ lymphoma patients who were resistant/refractory to cytotoxic therapy.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	87-90
24491302-6	2014	ALK mutations conferring resistance to crizotinib in vitro could be identified in relapsed patients.	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	0-3
24491302-7	2014	Crizotinib exerted a potent antitumor activity with durable responses in advanced, heavily pretreated ALK+ lymphoma patients, with a benign safety profile.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	102-105
24419423-1	2014	INTRODUCTION: Anaplastic lymphoma kinase (ALK) rearrangements are present in an important subset of non-small-cell lung cancer (NSCLC) and predict for response to the tyrosine kinase inhibitor crizotinib.	Crizotinib	193-203	ALK receptor tyrosine kinase	Homo sapiens	14-40
24419423-1	2014	INTRODUCTION: Anaplastic lymphoma kinase (ALK) rearrangements are present in an important subset of non-small-cell lung cancer (NSCLC) and predict for response to the tyrosine kinase inhibitor crizotinib.	Crizotinib	193-203	ALK receptor tyrosine kinase	Homo sapiens	42-45
24419423-5	2014	ALK splicing isoforms were observed with full-length EML4-ALK in crizotinib-naive and treated NSCLCs.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	0-3
24419423-5	2014	ALK splicing isoforms were observed with full-length EML4-ALK in crizotinib-naive and treated NSCLCs.	Crizotinib	65-75	EMAP like 4	Homo sapiens	53-57
24419423-5	2014	ALK splicing isoforms were observed with full-length EML4-ALK in crizotinib-naive and treated NSCLCs.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	58-61
24627688-1	2014	Rearrangement of anaplastic lymphoma kinase (ALK) gene is the best predictor of response to crizotinib, an ALK tyrosine kinase inhibitor.	Crizotinib	92-102	ALK receptor tyrosine kinase	Homo sapiens	17-43
24627688-1	2014	Rearrangement of anaplastic lymphoma kinase (ALK) gene is the best predictor of response to crizotinib, an ALK tyrosine kinase inhibitor.	Crizotinib	92-102	ALK receptor tyrosine kinase	Homo sapiens	45-48
24627688-1	2014	Rearrangement of anaplastic lymphoma kinase (ALK) gene is the best predictor of response to crizotinib, an ALK tyrosine kinase inhibitor.	Crizotinib	92-102	ALK receptor tyrosine kinase	Homo sapiens	107-110
24419060-9	2014	Finally, ASP3026 exhibited potent antitumor activity against cells expressing EML4-ALK with a mutation in the gatekeeper position (L1196M) that confers crizotinib resistance.	Crizotinib	152-162	EMAP like 4	Homo sapiens	78-82
24419060-9	2014	Finally, ASP3026 exhibited potent antitumor activity against cells expressing EML4-ALK with a mutation in the gatekeeper position (L1196M) that confers crizotinib resistance.	Crizotinib	152-162	ALK receptor tyrosine kinase	Homo sapiens	83-86
24670165-1	2014	BACKGROUND: Non-small-cell lung cancer (NSCLC) harboring the anaplastic lymphoma kinase gene (ALK) rearrangement is sensitive to the ALK inhibitor crizotinib, but resistance invariably develops.	Crizotinib	147-157	ALK receptor tyrosine kinase	Homo sapiens	133-136
24670165-6	2014	Tumor biopsies were performed before ceritinib treatment to identify resistance mutations in ALK in a group of patients with NSCLC who had had disease progression during treatment with crizotinib.	Crizotinib	185-195	ALK receptor tyrosine kinase	Homo sapiens	93-96
24444403-0	2014	Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small-cell lung cancer.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	56-59
24566025-3	2014	In the presence of EGFR mutation or ALK rearrangement, specific inhibitors have shown superior efficacy to chemotherapy in first-line treatment for anti-EGFR (erlotinib and gefitinib) and in second-line treatment for anti-ALK (crizotinib).	Crizotinib	227-237	epidermal growth factor receptor	Homo sapiens	19-23
24566025-3	2014	In the presence of EGFR mutation or ALK rearrangement, specific inhibitors have shown superior efficacy to chemotherapy in first-line treatment for anti-EGFR (erlotinib and gefitinib) and in second-line treatment for anti-ALK (crizotinib).	Crizotinib	227-237	ALK receptor tyrosine kinase	Homo sapiens	36-39
24565582-6	2014	A small-molecule TKI of anaplastic lymphoma kinase (ALK), crizotinib, showed pronounced clinical activity in the treatment of patients with NSCLC positive for EML4-ALK and it has rapidly entered into daily clinical practice.	Crizotinib	58-68	ALK receptor tyrosine kinase	Homo sapiens	24-50
24565582-6	2014	A small-molecule TKI of anaplastic lymphoma kinase (ALK), crizotinib, showed pronounced clinical activity in the treatment of patients with NSCLC positive for EML4-ALK and it has rapidly entered into daily clinical practice.	Crizotinib	58-68	ALK receptor tyrosine kinase	Homo sapiens	52-55
24565582-6	2014	A small-molecule TKI of anaplastic lymphoma kinase (ALK), crizotinib, showed pronounced clinical activity in the treatment of patients with NSCLC positive for EML4-ALK and it has rapidly entered into daily clinical practice.	Crizotinib	58-68	EMAP like 4	Homo sapiens	159-163
24565582-6	2014	A small-molecule TKI of anaplastic lymphoma kinase (ALK), crizotinib, showed pronounced clinical activity in the treatment of patients with NSCLC positive for EML4-ALK and it has rapidly entered into daily clinical practice.	Crizotinib	58-68	ALK receptor tyrosine kinase	Homo sapiens	164-167
24404167-1	2014	BACKGROUND: This study aimed to elucidate clinical significance of anaplastic lymphoma kinase (ALK) rearrangement in selected advanced non-small cell lung cancer (NSCLC), to compare the application of different ALK detection methods, and especially evaluate a possible association between ALK expression and clinical outcomes in crizotinib-treated patients.	Crizotinib	329-339	ALK receptor tyrosine kinase	Homo sapiens	95-98
24404167-4	2014	Moreover, the association of ALK expression with clinical outcomes was evaluated in ALK FISH-positive crizotinib-treated patients including two patients with concurrent epidermal growth factor receptor (EGFR) mutation.	Crizotinib	102-112	ALK receptor tyrosine kinase	Homo sapiens	29-32
23750540-0	2014	Crizotinib-induced acute interstitial lung disease in a patient with EML4-ALK positive non-small cell lung cancer and chronic interstitial pneumonia.	Crizotinib	0-10	EMAP like 4	Homo sapiens	69-73
23750540-0	2014	Crizotinib-induced acute interstitial lung disease in a patient with EML4-ALK positive non-small cell lung cancer and chronic interstitial pneumonia.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	74-77
24857124-7	2014	Similar to EGFR mutations, ALK rearrangements exemplify an oncogene-driven NSCLC that can be effectively palliated with a precision TKI therapy (the multitargeted ALK/MET/ROS1 TKI crizotinib).	Crizotinib	180-190	ALK receptor tyrosine kinase	Homo sapiens	27-30
24857124-8	2014	When resistance to first-line crizotinib therapy occurs, multiple second generation ALK TKIs have demonstrated impressive rates of disease control in clinical trials, and these may modify long-term outcomes for patients with ALK-positive NSCLC.	Crizotinib	30-40	ALK receptor tyrosine kinase	Homo sapiens	84-87
24857124-8	2014	When resistance to first-line crizotinib therapy occurs, multiple second generation ALK TKIs have demonstrated impressive rates of disease control in clinical trials, and these may modify long-term outcomes for patients with ALK-positive NSCLC.	Crizotinib	30-40	ALK receptor tyrosine kinase	Homo sapiens	225-228
24762619-0	2014	Severe acute interstitial lung disease induced by crizotinib therapy in a patient with c-Met amplification non-small cell lung cancer.	Crizotinib	50-60	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	87-92
24091716-1	2014	The identification of chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene in ~3-5% of non-small cell lung cancer (NSCLC) tissues and the demonstration that the first-in-class ALK tyrosine kinase inhibitor, crizotinib, can effectively target these tumors represent a significant advance in the evolution of personalized medicine for NSCLC.	Crizotinib	233-243	ALK receptor tyrosine kinase	Homo sapiens	63-89
24091716-1	2014	The identification of chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene in ~3-5% of non-small cell lung cancer (NSCLC) tissues and the demonstration that the first-in-class ALK tyrosine kinase inhibitor, crizotinib, can effectively target these tumors represent a significant advance in the evolution of personalized medicine for NSCLC.	Crizotinib	233-243	ALK receptor tyrosine kinase	Homo sapiens	91-94
24091716-1	2014	The identification of chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene in ~3-5% of non-small cell lung cancer (NSCLC) tissues and the demonstration that the first-in-class ALK tyrosine kinase inhibitor, crizotinib, can effectively target these tumors represent a significant advance in the evolution of personalized medicine for NSCLC.	Crizotinib	233-243	ALK receptor tyrosine kinase	Homo sapiens	202-205
23992325-6	2014	Clinical trials with several of these novel inhibitors have been encouraging and one of them, crizotinib (dual c-Met/ALK inhibitor), has recently been approved for lung cancers with ALK-rearrangement.	Crizotinib	94-104	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	111-116
23992325-6	2014	Clinical trials with several of these novel inhibitors have been encouraging and one of them, crizotinib (dual c-Met/ALK inhibitor), has recently been approved for lung cancers with ALK-rearrangement.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	117-120
23992325-6	2014	Clinical trials with several of these novel inhibitors have been encouraging and one of them, crizotinib (dual c-Met/ALK inhibitor), has recently been approved for lung cancers with ALK-rearrangement.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	182-185
25382190-3	2014	In recent years, there have been considerable efforts in the development of effective c-Met inhibitors with potential clinical-applications and one of them, crizotinib (dual c-Met/ALK inhibitor), has recently been approved for lung-cancers with ALKrearrangement.	Crizotinib	157-167	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	86-91
25382190-3	2014	In recent years, there have been considerable efforts in the development of effective c-Met inhibitors with potential clinical-applications and one of them, crizotinib (dual c-Met/ALK inhibitor), has recently been approved for lung-cancers with ALKrearrangement.	Crizotinib	157-167	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	174-179
25382190-3	2014	In recent years, there have been considerable efforts in the development of effective c-Met inhibitors with potential clinical-applications and one of them, crizotinib (dual c-Met/ALK inhibitor), has recently been approved for lung-cancers with ALKrearrangement.	Crizotinib	157-167	ALK receptor tyrosine kinase	Homo sapiens	180-183
24140933-0	2013	Crizotinib, a c-Met inhibitor, prevents metastasis in a metastatic uveal melanoma model.	Crizotinib	0-10	met proto-oncogene	Mus musculus	14-19
24199682-9	2014	Crizotinib+erlotinib (reversible EGFR TKI) and crizotinib+afatinib (irreversible EGFR/ERBB2 TKI) were able to inhibit the growth of H3122 CR clones, confirming EGFR activation as a mechanism of resistance.	Crizotinib	47-57	epidermal growth factor receptor	Homo sapiens	81-85
24649319-0	2014	Esophagitis resulting from treatment with crizotinib for anaplastic lymphoma kinase rearrangement-positive lung adenocarcinoma: A case report.	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	57-83
23910397-8	2014	Crizotinib 250mg BID was started.	Crizotinib	0-10	BH3 interacting domain death agonist	Homo sapiens	17-20
24386407-3	2013	EXPERIMENTAL DESIGN: Lung cancer cell lines made resistant to EGFR-TKIs by the gatekeeper EGFR-T790M mutation, Met amplification, and HGF overexpression and mice with tumors induced by these cells were treated with crizotinib and a new generation EGFR-TKI.	Crizotinib	215-225	epidermal growth factor receptor	Mus musculus	62-66
24386407-5	2013	In contrast, combined therapy with crizotinib plus afatinib or WZ4002 was effective against all three types of cells, inhibiting EGFR and Met phosphorylation and their downstream molecules.	Crizotinib	35-45	epidermal growth factor receptor	Mus musculus	129-133
24386407-8	2013	CONCLUSIONS: Our results suggest that the dual blockade of mutant EGFR and Met by crizotinib and a new generation EGFR-TKI may be promising for overcoming resistance to reversible EGFR-TKIs but careful assessment is warranted clinically.	Crizotinib	82-92	epidermal growth factor receptor	Mus musculus	66-70
24349229-5	2013	To accomplish this, we analyzed tumor samples from a patient who initially responded to the ROS1 inhibitor crizotinib but eventually developed acquired resistance.	Crizotinib	107-117	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	92-96
24121490-0	2013	The HSP90 inhibitor ganetespib synergizes with the MET kinase inhibitor crizotinib in both crizotinib-sensitive and -resistant MET-driven tumor models.	Crizotinib	72-82	heat shock protein 90 alpha family class A member 1	Homo sapiens	4-9
24121490-0	2013	The HSP90 inhibitor ganetespib synergizes with the MET kinase inhibitor crizotinib in both crizotinib-sensitive and -resistant MET-driven tumor models.	Crizotinib	91-101	heat shock protein 90 alpha family class A member 1	Homo sapiens	4-9
23551582-1	2013	OBJECTIVES: Patients with non-small cell lung cancer (NSCLC) positive for anaplastic lymphoma kinase (ALK) gene rearrangements may be treated successfully with the ALK inhibitor crizotinib.	Crizotinib	178-188	ALK receptor tyrosine kinase	Homo sapiens	74-100
23551582-1	2013	OBJECTIVES: Patients with non-small cell lung cancer (NSCLC) positive for anaplastic lymphoma kinase (ALK) gene rearrangements may be treated successfully with the ALK inhibitor crizotinib.	Crizotinib	178-188	ALK receptor tyrosine kinase	Homo sapiens	102-105
23551582-1	2013	OBJECTIVES: Patients with non-small cell lung cancer (NSCLC) positive for anaplastic lymphoma kinase (ALK) gene rearrangements may be treated successfully with the ALK inhibitor crizotinib.	Crizotinib	178-188	ALK receptor tyrosine kinase	Homo sapiens	164-167
24288180-0	2013	Crizotinib: a review of its use in the treatment of anaplastic lymphoma kinase-positive, advanced non-small cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	52-78
24288180-1	2013	Crizotinib (Xalkori( )) is an orally active, small molecule inhibitor of multiple receptor tyrosine kinases, including anaplastic lymphoma kinase (ALK), c-Met/hepatocyte growth factor receptor and c-ros oncogene 1.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	119-145
24288180-1	2013	Crizotinib (Xalkori( )) is an orally active, small molecule inhibitor of multiple receptor tyrosine kinases, including anaplastic lymphoma kinase (ALK), c-Met/hepatocyte growth factor receptor and c-ros oncogene 1.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	147-150
24288180-2	2013	In the EU, crizotinib has been conditionally approved for the treatment of adults with previously treated, ALK-positive, advanced non-small cell lung cancer (NSCLC).	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	107-110
24288180-7	2013	Crizotinib is the standard of care in terms of the treatment of patients with ALK-positive, advanced NSCLC; while the current EU approval is for second (or subsequent)-line use only, the first-line use of the drug is being evaluated in ongoing phase III studies.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	78-81
24192513-0	2014	Major partial response to crizotinib, a dual MET/ALK inhibitor, in a squamous cell lung (SCC) carcinoma patient with de novo c-MET amplification in the absence of ALK rearrangement.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	49-52
24192513-0	2014	Major partial response to crizotinib, a dual MET/ALK inhibitor, in a squamous cell lung (SCC) carcinoma patient with de novo c-MET amplification in the absence of ALK rearrangement.	Crizotinib	26-36	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	125-130
24192513-4	2014	The kinase inhibitor crizotinib is already in clinical use for the treatment of ALK positive non-small cell lung cancers, but it is also known to be a potent c-MET inhibitor.	Crizotinib	21-31	ALK receptor tyrosine kinase	Homo sapiens	80-83
24192513-4	2014	The kinase inhibitor crizotinib is already in clinical use for the treatment of ALK positive non-small cell lung cancers, but it is also known to be a potent c-MET inhibitor.	Crizotinib	21-31	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	158-163
24199682-0	2014	Dual ALK and EGFR inhibition targets a mechanism of acquired resistance to the tyrosine kinase inhibitor crizotinib in ALK rearranged lung cancer.	Crizotinib	105-115	ALK receptor tyrosine kinase	Homo sapiens	5-8
24199682-0	2014	Dual ALK and EGFR inhibition targets a mechanism of acquired resistance to the tyrosine kinase inhibitor crizotinib in ALK rearranged lung cancer.	Crizotinib	105-115	epidermal growth factor receptor	Homo sapiens	13-17
24199682-0	2014	Dual ALK and EGFR inhibition targets a mechanism of acquired resistance to the tyrosine kinase inhibitor crizotinib in ALK rearranged lung cancer.	Crizotinib	105-115	ALK receptor tyrosine kinase	Homo sapiens	119-122
24199682-1	2014	INTRODUCTION: The multitargeted tyrosine kinase inhibitor (TKI) crizotinib is active against ALK translocated non-small-cell lung cancer (NSCLC); however acquired resistance invariably develops over time.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	93-96
24199682-8	2014	A functional approach of dual ALK TKI (with crizotinib) with combinatory TKI inhibition was used as a secondary screen for possible targets.	Crizotinib	44-54	ALK receptor tyrosine kinase	Homo sapiens	30-33
24199682-9	2014	Crizotinib+erlotinib (reversible EGFR TKI) and crizotinib+afatinib (irreversible EGFR/ERBB2 TKI) were able to inhibit the growth of H3122 CR clones, confirming EGFR activation as a mechanism of resistance.	Crizotinib	0-10	epidermal growth factor receptor	Homo sapiens	33-37
24199682-9	2014	Crizotinib+erlotinib (reversible EGFR TKI) and crizotinib+afatinib (irreversible EGFR/ERBB2 TKI) were able to inhibit the growth of H3122 CR clones, confirming EGFR activation as a mechanism of resistance.	Crizotinib	47-57	erb-b2 receptor tyrosine kinase 2	Homo sapiens	86-91
24199682-9	2014	Crizotinib+erlotinib (reversible EGFR TKI) and crizotinib+afatinib (irreversible EGFR/ERBB2 TKI) were able to inhibit the growth of H3122 CR clones, confirming EGFR activation as a mechanism of resistance.	Crizotinib	47-57	epidermal growth factor receptor	Homo sapiens	81-85
24199682-11	2014	CONCLUSIONS: We identified activation of EGFR as a mechanism of resistance to crizotinib in preclinical models of ALK translocated NSCLC.	Crizotinib	78-88	epidermal growth factor receptor	Homo sapiens	41-45
24199682-11	2014	CONCLUSIONS: We identified activation of EGFR as a mechanism of resistance to crizotinib in preclinical models of ALK translocated NSCLC.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	114-117
24170771-3	2014	Fifty percent of the thyroid cancer cell lines (four of eight) were growth inhibited by two small molecule c-MET inhibitors (tivantinib and crizotinib) associated with apoptosis and G(2)-M cell-cycle arrest.	Crizotinib	140-150	met proto-oncogene	Mus musculus	107-112
24170771-9	2014	In summary, c-MET inhibitors (tivantinib and crizotinib) suppress the growth of aggressive thyroid cancer cells, and this potential therapeutic benefit results from their non-MET-targeting effects.	Crizotinib	45-55	met proto-oncogene	Mus musculus	12-17
25115320-0	2014	Response to chemotherapy, reexposure to crizotinib and treatment with a novel ALK inhibitor in a patient with acquired crizotinib resistance.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	78-81
25115320-3	2014	Crizotinib is a new tyrosine kinase inhibitor approved for the treatment of NSCLC with gene rearrangement of EML4 and ALK.	Crizotinib	0-10	EMAP like 4	Homo sapiens	109-113
25115320-3	2014	Crizotinib is a new tyrosine kinase inhibitor approved for the treatment of NSCLC with gene rearrangement of EML4 and ALK.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	118-121
25115320-6	2014	This is the second case report to suggest that retreatment with crizotinib is an option for patients with initial benefit from ALK inhibition.	Crizotinib	64-74	ALK receptor tyrosine kinase	Homo sapiens	127-130
24386407-0	2013	Ability of the Met kinase inhibitor crizotinib and new generation EGFR inhibitors to overcome resistance to EGFR inhibitors.	Crizotinib	36-46	epidermal growth factor receptor	Mus musculus	108-112
24386407-2	2013	We therefore assessed the ability of combined treatment with the Met inhibitor crizotinib and new generation EGFR-TKIs to overcome resistance to first-generation EGFR-TKIs.	Crizotinib	79-89	epidermal growth factor receptor	Mus musculus	162-166
24118504-9	2013	MET tyrosine kinase inhibitors, crizotinib and TAS-115, inhibited HGF-stimulated proliferation of NUGC4 and GCIY as well as constitutive proliferation of MKN45.	Crizotinib	32-42	hepatocyte growth factor	Homo sapiens	66-69
23993685-0	2013	Epithelial-mesenchymal transition leads to crizotinib resistance in H2228 lung cancer cells with EML4-ALK translocation.	Crizotinib	43-53	EMAP like 4	Homo sapiens	97-101
23993685-0	2013	Epithelial-mesenchymal transition leads to crizotinib resistance in H2228 lung cancer cells with EML4-ALK translocation.	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	102-105
23993685-2	2013	Here, we investigated if this reduced sensitivity also contributes to resistance to crizotinib, an ALK inhibitor of lung cancer that exhibits the EML4-ALK translocation.	Crizotinib	84-94	ALK receptor tyrosine kinase	Homo sapiens	99-102
23993685-2	2013	Here, we investigated if this reduced sensitivity also contributes to resistance to crizotinib, an ALK inhibitor of lung cancer that exhibits the EML4-ALK translocation.	Crizotinib	84-94	EMAP like 4	Homo sapiens	146-150
23993685-2	2013	Here, we investigated if this reduced sensitivity also contributes to resistance to crizotinib, an ALK inhibitor of lung cancer that exhibits the EML4-ALK translocation.	Crizotinib	84-94	ALK receptor tyrosine kinase	Homo sapiens	151-154
23993685-9	2013	Applying TGF-beta1 treatment to parental H2228 cells for 72 h induced reversible EMT, leading to crizotinib resistance, but this was reversed by the removal of TGF-beta1.	Crizotinib	97-107	transforming growth factor beta 1	Homo sapiens	9-18
23993685-10	2013	Suppression of vimentin in H2228/CR cells by siRNA treatment restored sensitivity to crizotinib.	Crizotinib	85-95	vimentin	Homo sapiens	15-23
24140933-2	2013	Crizotinib, an inhibitor of c-Met, anaplastic lymphoma kinase (ALK), and ROS1, inhibited the phosphorylation of the c-Met receptor but not of ALK or ROS1 in uveal melanoma cells and tumor tissue.	Crizotinib	0-10	met proto-oncogene	Mus musculus	28-33
24140933-2	2013	Crizotinib, an inhibitor of c-Met, anaplastic lymphoma kinase (ALK), and ROS1, inhibited the phosphorylation of the c-Met receptor but not of ALK or ROS1 in uveal melanoma cells and tumor tissue.	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	35-61
24140933-2	2013	Crizotinib, an inhibitor of c-Met, anaplastic lymphoma kinase (ALK), and ROS1, inhibited the phosphorylation of the c-Met receptor but not of ALK or ROS1 in uveal melanoma cells and tumor tissue.	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	63-66
24140933-2	2013	Crizotinib, an inhibitor of c-Met, anaplastic lymphoma kinase (ALK), and ROS1, inhibited the phosphorylation of the c-Met receptor but not of ALK or ROS1 in uveal melanoma cells and tumor tissue.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	116-121
24140933-8	2013	These results indicate that the inhibition of c-Met activity alone may be sufficient to strongly inhibit metastasis of uveal melanoma from forming, suggesting crizotinib as a potential adjuvant therapy for patients with primary uveal melanoma who are at high risk for the development of metastatic disease.	Crizotinib	159-169	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	46-51
24345493-4	2013	Crizotinib demonstrates in vitro activity and early clinical trial shows marked antitumor activity in ROS1-rearranged patients.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	102-106
24220141-10	2013	The c-Met inhibitor crizotinib reduced MACC1-induced migration and tumor formation in organotypic hippocampal slice cultures of mice.	Crizotinib	20-30	met proto-oncogene	Mus musculus	4-9
24220141-10	2013	The c-Met inhibitor crizotinib reduced MACC1-induced migration and tumor formation in organotypic hippocampal slice cultures of mice.	Crizotinib	20-30	metastasis associated in colon cancer 1	Mus musculus	39-44
24163262-8	2013	Crizotinib, an FDA-approved ALK inhibitor, reduced keratinocyte proliferation in culture, whereas a c-Met inhibitor did not.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	28-31
24163262-9	2013	Crizotinib significantly reduced the expression of GLI1 and CCND2 (members of SHH-pathway) mRNA by approximately 60% and 20%, respectively (p<0.01).	Crizotinib	0-10	GLI family zinc finger 1	Homo sapiens	51-55
24163262-9	2013	Crizotinib significantly reduced the expression of GLI1 and CCND2 (members of SHH-pathway) mRNA by approximately 60% and 20%, respectively (p<0.01).	Crizotinib	0-10	cyclin D2	Homo sapiens	60-65
24163262-9	2013	Crizotinib significantly reduced the expression of GLI1 and CCND2 (members of SHH-pathway) mRNA by approximately 60% and 20%, respectively (p<0.01).	Crizotinib	0-10	sonic hedgehog signaling molecule	Homo sapiens	78-81
24218589-3	2013	Whereas crizotinib has demonstrated promising early results in patients with ROS1-rearranged non-small-cell lung carcinoma, recently emerging clinical evidence suggests that patients may develop crizotinib resistance due to acquired point mutations in the kinase domain of ROS1, thus necessitating identification of additional potent ROS1 inhibitors for therapeutic intervention.	Crizotinib	8-18	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	77-81
24279718-0	2013	Concomitant occurrence of EGFR (epidermal growth factor receptor) and KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in an ALK (anaplastic lymphoma kinase)-positive lung adenocarcinoma patient with acquired resistance to crizotinib: a case report.	Crizotinib	244-254	epidermal growth factor receptor	Rattus norvegicus	26-30
24279718-0	2013	Concomitant occurrence of EGFR (epidermal growth factor receptor) and KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in an ALK (anaplastic lymphoma kinase)-positive lung adenocarcinoma patient with acquired resistance to crizotinib: a case report.	Crizotinib	244-254	KRAS proto-oncogene, GTPase	Rattus norvegicus	70-74
24279718-0	2013	Concomitant occurrence of EGFR (epidermal growth factor receptor) and KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in an ALK (anaplastic lymphoma kinase)-positive lung adenocarcinoma patient with acquired resistance to crizotinib: a case report.	Crizotinib	244-254	ALK receptor tyrosine kinase	Rattus norvegicus	146-149
24279718-0	2013	Concomitant occurrence of EGFR (epidermal growth factor receptor) and KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in an ALK (anaplastic lymphoma kinase)-positive lung adenocarcinoma patient with acquired resistance to crizotinib: a case report.	Crizotinib	244-254	ALK receptor tyrosine kinase	Rattus norvegicus	151-177
24279718-1	2013	BACKGROUND: Anaplastic lymphoma kinase-positive non-small cell lung carcinoma patients are generally highly responsive to the dual anaplastic lymphoma kinase and MET tyrosine kinase inhibitor crizotinib.	Crizotinib	192-202	ALK receptor tyrosine kinase	Rattus norvegicus	12-38
24279718-3	2013	The molecular mechanisms responsible for crizotinib resistance are beginning to emerge, e.g., in some anaplastic lymphoma kinase-positive non-small cell lung carcinomas the development of secondary mutations in this gene has been described.	Crizotinib	41-51	ALK receptor tyrosine kinase	Rattus norvegicus	102-128
24279718-5	2013	Thus, we report on an anaplastic lymphoma kinase-positive non-small cell lung carcinoma patient with concomitant occurrence of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations upon development of crizotinib-resistance.	Crizotinib	247-257	ALK receptor tyrosine kinase	Rattus norvegicus	22-48
24279718-5	2013	Thus, we report on an anaplastic lymphoma kinase-positive non-small cell lung carcinoma patient with concomitant occurrence of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations upon development of crizotinib-resistance.	Crizotinib	247-257	epidermal growth factor receptor	Homo sapiens	127-159
24279718-9	2013	CONCLUSION: To our knowledge, this is the first report of an anaplastic lymphoma kinase-positive pulmonary adenocarcinoma, which upon emergence of crizotinib resistance acquired 2 new somatic mutations in the epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog genes, respectively, concomitant with the original anaplastic lymphoma kinase rearrangement.	Crizotinib	147-157	ALK receptor tyrosine kinase	Rattus norvegicus	61-87
24279718-9	2013	CONCLUSION: To our knowledge, this is the first report of an anaplastic lymphoma kinase-positive pulmonary adenocarcinoma, which upon emergence of crizotinib resistance acquired 2 new somatic mutations in the epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog genes, respectively, concomitant with the original anaplastic lymphoma kinase rearrangement.	Crizotinib	147-157	epidermal growth factor receptor	Rattus norvegicus	209-241
24279718-9	2013	CONCLUSION: To our knowledge, this is the first report of an anaplastic lymphoma kinase-positive pulmonary adenocarcinoma, which upon emergence of crizotinib resistance acquired 2 new somatic mutations in the epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog genes, respectively, concomitant with the original anaplastic lymphoma kinase rearrangement.	Crizotinib	147-157	ALK receptor tyrosine kinase	Rattus norvegicus	350-376
24218589-3	2013	Whereas crizotinib has demonstrated promising early results in patients with ROS1-rearranged non-small-cell lung carcinoma, recently emerging clinical evidence suggests that patients may develop crizotinib resistance due to acquired point mutations in the kinase domain of ROS1, thus necessitating identification of additional potent ROS1 inhibitors for therapeutic intervention.	Crizotinib	195-205	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	273-277
24218589-3	2013	Whereas crizotinib has demonstrated promising early results in patients with ROS1-rearranged non-small-cell lung carcinoma, recently emerging clinical evidence suggests that patients may develop crizotinib resistance due to acquired point mutations in the kinase domain of ROS1, thus necessitating identification of additional potent ROS1 inhibitors for therapeutic intervention.	Crizotinib	195-205	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	273-277
24218589-4	2013	We confirm that the ROS1(G2032R) mutant, recently reported in clinical resistance to crizotinib, retains foretinib sensitivity at concentrations below safe, clinically achievable levels.	Crizotinib	85-95	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	20-24
24218589-5	2013	Furthermore, we use an accelerated mutagenesis screen to preemptively identify mutations in the ROS1 kinase domain that confer resistance to crizotinib and demonstrate that these mutants also remain foretinib sensitive.	Crizotinib	141-151	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	96-100
24085787-0	2013	Crizotinib inhibits metabolic inactivation of gemcitabine in c-Met-driven pancreatic carcinoma.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	61-66
24389440-1	2013	Anaplastic lymphoma kinase (ALK) gene rearrangements define a distinct molecular subset of non-small-cell lung cancer that is highly responsive to treatment with the ALK inhibitor crizotinib.	Crizotinib	180-190	ALK receptor tyrosine kinase	Homo sapiens	0-26
24389440-1	2013	Anaplastic lymphoma kinase (ALK) gene rearrangements define a distinct molecular subset of non-small-cell lung cancer that is highly responsive to treatment with the ALK inhibitor crizotinib.	Crizotinib	180-190	ALK receptor tyrosine kinase	Homo sapiens	28-31
24389440-1	2013	Anaplastic lymphoma kinase (ALK) gene rearrangements define a distinct molecular subset of non-small-cell lung cancer that is highly responsive to treatment with the ALK inhibitor crizotinib.	Crizotinib	180-190	ALK receptor tyrosine kinase	Homo sapiens	166-169
24389440-2	2013	Recently, it has been recognized that the brain is a frequent site of relapse among ALK-positive patients treated with crizotinib.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	84-87
24389446-0	2013	Choroidal metastases responsive to crizotinib therapy in a lung adenocarcinoma patient with ALK 2p23 fusion identified by ALK immunohistochemistry.	Crizotinib	35-45	activin A receptor type 1	Homo sapiens	92-98
24389446-0	2013	Choroidal metastases responsive to crizotinib therapy in a lung adenocarcinoma patient with ALK 2p23 fusion identified by ALK immunohistochemistry.	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	92-95
24389447-0	2013	Effective crizotinib schedule for brain metastases in ALK rearrangement metastatic non-small-cell lung cancer.	Crizotinib	10-20	ALK receptor tyrosine kinase	Homo sapiens	54-57
23962905-7	2013	In vivo, the combination therapy with crizotinib and gefitinib also markedly suppressed the growth of gefitinib-resistant mouse xenografts established by injecting HCC827 cells mixed with HGF-producing fibroblasts (MRC-5 cells) subcutaneously into severe combined immunodeficient mice.	Crizotinib	38-48	hepatocyte growth factor	Homo sapiens	188-191
23962905-8	2013	In conclusion, these findings provided preclinical evidence that crizotinib can be used in the treatment of HGF-induced resistance to gefitinib in EGFR mutant lung cancer.	Crizotinib	65-75	hepatocyte growth factor	Homo sapiens	108-111
23962905-8	2013	In conclusion, these findings provided preclinical evidence that crizotinib can be used in the treatment of HGF-induced resistance to gefitinib in EGFR mutant lung cancer.	Crizotinib	65-75	epidermal growth factor receptor	Homo sapiens	147-151
23931899-1	2013	BACKGROUND: Crizotinib produces high response rates and prolonged PFS in ALK+ NSCLC.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	73-76
23931899-11	2013	CONCLUSION: Crizotinib and pemetrexed are active drugs in ALK+ NSCLC.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	58-61
24088065-4	2013	AREAS COVERED: This article describes the clinical development of epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs) and crizotinib for EGFR-mutant and anaplastic lymphoma kinase (ALK)-rearranged NSCLC.	Crizotinib	133-143	epidermal growth factor receptor	Homo sapiens	148-152
24088065-4	2013	AREAS COVERED: This article describes the clinical development of epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs) and crizotinib for EGFR-mutant and anaplastic lymphoma kinase (ALK)-rearranged NSCLC.	Crizotinib	133-143	ALK receptor tyrosine kinase	Homo sapiens	164-190
24088065-4	2013	AREAS COVERED: This article describes the clinical development of epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs) and crizotinib for EGFR-mutant and anaplastic lymphoma kinase (ALK)-rearranged NSCLC.	Crizotinib	133-143	ALK receptor tyrosine kinase	Homo sapiens	192-195
24001942-2	2013	Following identification of a mutation of the echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) gene, crizotinib was then administered as targeted treatment.	Crizotinib	139-149	EMAP like 4	Homo sapiens	123-127
23962905-0	2013	Crizotinib overcomes hepatocyte growth factor-mediated resistance to gefitinib in EGFR-mutant non-small-cell lung cancer cells.	Crizotinib	0-10	hepatocyte growth factor	Homo sapiens	21-45
23962905-0	2013	Crizotinib overcomes hepatocyte growth factor-mediated resistance to gefitinib in EGFR-mutant non-small-cell lung cancer cells.	Crizotinib	0-10	epidermal growth factor receptor	Homo sapiens	82-86
23962905-4	2013	Here, we tested whether crizotinib (PF02341066), a MET kinase inhibitor, can overcome two different HGF-triggered mechanisms of resistance to gefitinib in human EGFR mutant lung cancer cell lines HCC827 and PC-9.	Crizotinib	24-34	hepatocyte growth factor	Homo sapiens	100-103
23962905-4	2013	Here, we tested whether crizotinib (PF02341066), a MET kinase inhibitor, can overcome two different HGF-triggered mechanisms of resistance to gefitinib in human EGFR mutant lung cancer cell lines HCC827 and PC-9.	Crizotinib	24-34	epidermal growth factor receptor	Homo sapiens	161-165
23962905-5	2013	Compared with the monotherapy, the combined treatment of crizotinib and gefitinib induced apoptosis and significantly inhibited the growth of cells in the presence of HGF by blocking the MET/PI3K/Akt pathway.	Crizotinib	57-67	hepatocyte growth factor	Homo sapiens	167-170
23962905-5	2013	Compared with the monotherapy, the combined treatment of crizotinib and gefitinib induced apoptosis and significantly inhibited the growth of cells in the presence of HGF by blocking the MET/PI3K/Akt pathway.	Crizotinib	57-67	AKT serine/threonine kinase 1	Homo sapiens	196-199
23962905-6	2013	Further, we demonstrated that crizotinib plus gefitinib successfully prevented the emergence of gefitinib-resistant HCC827 cells induced by transient exposure to HGF.	Crizotinib	30-40	hepatocyte growth factor	Homo sapiens	162-165
23801497-1	2013	BACKGROUND: Crizotinib, a dual anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition (MET) tyrosine kinase inhibitor, is currently being evaluated for the treatment of neuroblastoma.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	31-57
23801497-1	2013	BACKGROUND: Crizotinib, a dual anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition (MET) tyrosine kinase inhibitor, is currently being evaluated for the treatment of neuroblastoma.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	59-62
24128725-0	2013	Dramatic response to crizotinib in an ALK-positive adenocarcinoma patient with disseminated intravascular coagulation.	Crizotinib	21-31	ALK receptor tyrosine kinase	Homo sapiens	38-41
24166094-6	2013	Most recently, pediatric phase I testing has been completed for the first approved ALK inhibitor, Crizotinib, showing very encouraging antitumoral results in neuroblastoma patients.	Crizotinib	98-108	ALK receptor tyrosine kinase	Homo sapiens	83-86
24001942-2	2013	Following identification of a mutation of the echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) gene, crizotinib was then administered as targeted treatment.	Crizotinib	139-149	ALK receptor tyrosine kinase	Homo sapiens	128-131
24192124-3	2013	EGFR mutation as well as KRAS and ALK rearrangements are important biomarkers in the field owing to potential targeted therapies involved in clinical practice: erlotinib, geftinib, cetuximab and crizotinib.	Crizotinib	195-205	epidermal growth factor receptor	Homo sapiens	0-4
24192124-3	2013	EGFR mutation as well as KRAS and ALK rearrangements are important biomarkers in the field owing to potential targeted therapies involved in clinical practice: erlotinib, geftinib, cetuximab and crizotinib.	Crizotinib	195-205	ALK receptor tyrosine kinase	Homo sapiens	34-37
24102046-7	2013	The small molecule dual tyrosine kinase cMET/ALK inhibitor, Crizotinib (PF-02341066/Xalkori , Pfizer Inc), induced both cytotoxicity (IC50 = 0.89 muM) and apoptosis, with abrogation of pALK signaling in IBC tumor cells and in FC-IBC01 tumor xenograft model, a new IBC model derived from pleural effusion cells isolated from an ALK(+) IBC patient.	Crizotinib	60-70	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	40-44
24229629-3	2013	However, in squamous cell lung cancer, the incidence of epidermal growth factor receptor (EGFR) gene mutant and ALK fusion gene are low,and targeted therapy like Tarceva and crizotinib, can hardly work.	Crizotinib	174-184	ALK receptor tyrosine kinase	Homo sapiens	112-115
24060861-2	2013	The common activation of ALK has led to the use of the ALK tyrosine kinase inhibitor (TKI) crizotinib in a range of patient populations and to the rapid development of second-generation drugs targeting ALK.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	25-28
24060861-2	2013	The common activation of ALK has led to the use of the ALK tyrosine kinase inhibitor (TKI) crizotinib in a range of patient populations and to the rapid development of second-generation drugs targeting ALK.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	55-58
24060861-2	2013	The common activation of ALK has led to the use of the ALK tyrosine kinase inhibitor (TKI) crizotinib in a range of patient populations and to the rapid development of second-generation drugs targeting ALK.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	55-58
24102046-7	2013	The small molecule dual tyrosine kinase cMET/ALK inhibitor, Crizotinib (PF-02341066/Xalkori , Pfizer Inc), induced both cytotoxicity (IC50 = 0.89 muM) and apoptosis, with abrogation of pALK signaling in IBC tumor cells and in FC-IBC01 tumor xenograft model, a new IBC model derived from pleural effusion cells isolated from an ALK(+) IBC patient.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	45-48
24102046-7	2013	The small molecule dual tyrosine kinase cMET/ALK inhibitor, Crizotinib (PF-02341066/Xalkori , Pfizer Inc), induced both cytotoxicity (IC50 = 0.89 muM) and apoptosis, with abrogation of pALK signaling in IBC tumor cells and in FC-IBC01 tumor xenograft model, a new IBC model derived from pleural effusion cells isolated from an ALK(+) IBC patient.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	186-189
23952683-0	2013	Insight into crizotinib resistance mechanisms caused by three mutations in ALK tyrosine kinase using free energy calculation approaches.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	75-78
23952683-3	2013	Several drug resistance mutations have been found in the anaplastic lymphoma kinase (ALK) tyrosine kinase domain as the target for crizotinib, but the drug resistance mechanisms remain unclear.	Crizotinib	131-141	ALK receptor tyrosine kinase	Homo sapiens	57-83
23952683-3	2013	Several drug resistance mutations have been found in the anaplastic lymphoma kinase (ALK) tyrosine kinase domain as the target for crizotinib, but the drug resistance mechanisms remain unclear.	Crizotinib	131-141	ALK receptor tyrosine kinase	Homo sapiens	85-88
23952683-5	2013	The ABF simulation results suggest that the reaction coordinates for the unbinding processes of crizotinib from the binding pockets of the mutated ALKs is different from that of the wild type ALK.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	147-150
24047072-0	2013	Acquired resistance to crizotinib from a mutation in CD74-ROS1.	Crizotinib	23-33	CD74 molecule	Homo sapiens	53-57
24047072-0	2013	Acquired resistance to crizotinib from a mutation in CD74-ROS1.	Crizotinib	23-33	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	58-62
24047073-0	2013	Acquired resistance to crizotinib from a mutation in CD74-ROS1.	Crizotinib	23-33	CD74 molecule	Homo sapiens	53-57
24047073-0	2013	Acquired resistance to crizotinib from a mutation in CD74-ROS1.	Crizotinib	23-33	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	58-62
24022905-0	2013	Long-lasting response to crizotinib in brain metastases due to EML4-ALK-rearranged non-small-cell lung cancer.	Crizotinib	25-35	EMAP like 4	Homo sapiens	63-67
24022905-0	2013	Long-lasting response to crizotinib in brain metastases due to EML4-ALK-rearranged non-small-cell lung cancer.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	68-71
24022905-1	2013	Anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC) is highly responsive to crizotinib, an oral ATP-competitive selective inhibitor of ALK.	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	0-26
24022905-1	2013	Anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC) is highly responsive to crizotinib, an oral ATP-competitive selective inhibitor of ALK.	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	28-31
24022905-1	2013	Anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC) is highly responsive to crizotinib, an oral ATP-competitive selective inhibitor of ALK.	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	162-165
24022905-7	2013	To our knowledge, the present case is the second report of crizotinib-responsive brain metastases due to echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK)-rearranged NSCLC.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	154-157
23898821-5	2013	Replicate quantifications by mTRAQ identified almost as many significant phosphorylation changes upon treatment with ALK kinase inhibitor crizotinib as found by SILAC quantification.	Crizotinib	138-148	ALK receptor tyrosine kinase	Homo sapiens	117-120
23898821-8	2013	Further inspection of crizotinib-regulated phosphorylation changes unveiled interference with multiple antioncogenic mechanisms downstream of ALK fusion kinase in H3122 cells.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	142-145
23880539-4	2013	This binding mode is in contrast to that of known ALK inhibitors such as Crizotinib and NVP-TAE684 which occupy the ribose binding pocket, close to DFG motif.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	50-53
23612660-7	2013	These cells were more sensitive to crizotinib, an ALK inhibitor compared with PC-9 and H460 cells without EML4-ALK rearrangement.	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	50-53
23790969-2	2013	Crizotinib is an oral tyrosine kinase inhibitor targeting ALK, met proto-oncogene, and c-ros oncogene 1 (ROS1).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	58-61
23790969-2	2013	Crizotinib is an oral tyrosine kinase inhibitor targeting ALK, met proto-oncogene, and c-ros oncogene 1 (ROS1).	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	87-103
23790969-2	2013	Crizotinib is an oral tyrosine kinase inhibitor targeting ALK, met proto-oncogene, and c-ros oncogene 1 (ROS1).	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	105-109
23790969-4	2013	In 2012, results from the first phase III trial showing superiority of crizotinib compared with standard chemotherapy in second-line treatment of ALK-positive NSCLC were presented.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	146-149
23790969-5	2013	Furthermore, crizotinib was recently shown to be active in ROS1-rearranged NSCLC.	Crizotinib	13-23	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	59-63
23790969-6	2013	Here, we give an overview of the molecular pathogenesis of ALK-rearranged NSCLC, the pharmacokinetic and pharmacodynamic properties of crizotinib, and clinical trials of crizotinib for ALK-rearranged NSCLC.	Crizotinib	170-180	ALK receptor tyrosine kinase	Homo sapiens	185-188
23805942-3	2013	AREAS COVERED: The author provides a review of the development of crizotinib, an orally effective c-Met and ALK protein kinase inhibitor.	Crizotinib	66-76	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	98-103
23805942-3	2013	AREAS COVERED: The author provides a review of the development of crizotinib, an orally effective c-Met and ALK protein kinase inhibitor.	Crizotinib	66-76	ALK receptor tyrosine kinase	Homo sapiens	108-111
23805942-5	2013	EXPERT OPINION: Studies of patients with EML4-ALK-positive NSCLC showed that crizotinib was clinically effective and led to its approval in August 2011.	Crizotinib	77-87	EMAP like 4	Homo sapiens	41-45
23805942-5	2013	EXPERT OPINION: Studies of patients with EML4-ALK-positive NSCLC showed that crizotinib was clinically effective and led to its approval in August 2011.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	46-49
23805942-6	2013	The use of lipophilic efficiency played a crucial role in the development of crizotinib from a lead c-Met inhibitor.	Crizotinib	77-87	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	100-105
23434628-0	2013	Multiplexed deep sequencing analysis of ALK kinase domain identifies resistance mutations in relapsed patients following crizotinib treatment.	Crizotinib	121-131	ALK receptor tyrosine kinase	Homo sapiens	40-43
23434628-1	2013	The recently approved ALK kinase inhibitor crizotinib has demonstrated successful treatment of metastatic and late stage ALK fusion positive non-small cell lung cancer (NSCLC).	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	22-25
23434628-1	2013	The recently approved ALK kinase inhibitor crizotinib has demonstrated successful treatment of metastatic and late stage ALK fusion positive non-small cell lung cancer (NSCLC).	Crizotinib	43-53	ALK receptor tyrosine kinase	Homo sapiens	121-124
23434628-3	2013	Mutations in the ALK kinase domain confer resistance to crizotinib in about one-third of these patients.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	17-20
23809060-0	2013	Mechanisms of resistance to EGFR tyrosine kinase inhibitors gefitinib/erlotinib and to ALK inhibitor crizotinib.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	87-90
23809060-2	2013	In particular, gefitinib and erlotinib have become the standard of care in patients harboring epidermal growth factor receptor mutations, while crizotinib showed an impressive efficacy in patients with ALK-positive NSCLC.	Crizotinib	144-154	ALK receptor tyrosine kinase	Homo sapiens	202-205
24022905-7	2013	To our knowledge, the present case is the second report of crizotinib-responsive brain metastases due to echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK)-rearranged NSCLC.	Crizotinib	59-69	EMAP like 4	Homo sapiens	159-163
24022905-7	2013	To our knowledge, the present case is the second report of crizotinib-responsive brain metastases due to echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK)-rearranged NSCLC.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	164-167
23769207-1	2013	The recent approval of crizotinib for the treatment of anaplastic lymphoma kinase (ALK)-rearranged advanced non-small cell lung cancer (NSCLC) in the US and other countries has provoked intense interest in ALK rearrangements as oncogenic drivers, and promises to revolutionise the way in which NSCLC is diagnosed and treated.	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	55-81
23881038-1	2013	Rearrangements of the ALK gene have been associated with sensitivity to crizotinib and other kinase inhibitors with activity against ALK.	Crizotinib	72-82	ALK receptor tyrosine kinase	Homo sapiens	22-25
23881038-2	2013	The phase III PROFILE 1007 randomized study of crizotinib versus chemotherapy has demonstrated that crizotinib is superior to standard second-line chemotherapy in ALK-positive non-small-cell lung cancer.	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	163-166
24362875-0	2013	Fishing for ALK with immunohistochemistry may predict response to crizotinib.	Crizotinib	66-76	ALK receptor tyrosine kinase	Homo sapiens	12-15
24362875-1	2013	BACKGROUND: ALK (anaplastic lymphoma kinase) gene rearrangement is a novel oncogenic driver in non-small cell lung cancer (NSCLC) against which a selective inhibitor, namely crizotinib, is effective.	Crizotinib	174-184	ALK receptor tyrosine kinase	Homo sapiens	12-15
24362875-1	2013	BACKGROUND: ALK (anaplastic lymphoma kinase) gene rearrangement is a novel oncogenic driver in non-small cell lung cancer (NSCLC) against which a selective inhibitor, namely crizotinib, is effective.	Crizotinib	174-184	ALK receptor tyrosine kinase	Homo sapiens	17-43
24362875-2	2013	Fluorescence in situ hybridization (FISH) is considered the reference method in selecting patients with ALK-positive tumors for treatment with crizotinib.	Crizotinib	143-153	ALK receptor tyrosine kinase	Homo sapiens	104-107
23951022-1	2013	BACKGROUND: Recently Echinoderm microtubule-associated protein-like 4- anaplastic lymphoma kinase (EML4-ALK) fusion gene has become an important biomarker for ALK tyrosine kinase inhibitor (crizotinib) treatment in NSCLC.	Crizotinib	190-200	EMAP like 4	Homo sapiens	99-103
23951022-1	2013	BACKGROUND: Recently Echinoderm microtubule-associated protein-like 4- anaplastic lymphoma kinase (EML4-ALK) fusion gene has become an important biomarker for ALK tyrosine kinase inhibitor (crizotinib) treatment in NSCLC.	Crizotinib	190-200	ALK receptor tyrosine kinase	Homo sapiens	104-107
23951022-1	2013	BACKGROUND: Recently Echinoderm microtubule-associated protein-like 4- anaplastic lymphoma kinase (EML4-ALK) fusion gene has become an important biomarker for ALK tyrosine kinase inhibitor (crizotinib) treatment in NSCLC.	Crizotinib	190-200	ALK receptor tyrosine kinase	Homo sapiens	159-162
23719267-5	2013	Targeting ROS1 fusion proteins with the small-molecule inhibitor crizotinib is showing promise as an effective therapy in patients with NSCLC whose tumors are positive for these genetic abnormalities.	Crizotinib	65-75	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	10-14
23729361-2	2013	Recently, several case reports and small series have reported that ALK rearrangements can overlap with other oncogenic drivers in NSCLC in crizotinib-naive and crizotinib-resistant cancers.	Crizotinib	139-149	ALK receptor tyrosine kinase	Homo sapiens	67-70
23729361-2	2013	Recently, several case reports and small series have reported that ALK rearrangements can overlap with other oncogenic drivers in NSCLC in crizotinib-naive and crizotinib-resistant cancers.	Crizotinib	160-170	ALK receptor tyrosine kinase	Homo sapiens	67-70
23729361-4	2013	We also examined biopsy specimens from 34 patients with ALK-positive NSCLC after the development of resistance to crizotinib.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	56-59
23729361-9	2013	Among patients with ALK-positive NSCLC who acquired resistance to crizotinib, repeat biopsy specimens were ALK FISH positive in 29 of 29 (100%) cases.	Crizotinib	66-76	ALK receptor tyrosine kinase	Homo sapiens	20-23
23729361-9	2013	Among patients with ALK-positive NSCLC who acquired resistance to crizotinib, repeat biopsy specimens were ALK FISH positive in 29 of 29 (100%) cases.	Crizotinib	66-76	ALK receptor tyrosine kinase	Homo sapiens	107-110
23585220-1	2013	BACKGROUND: Crizotinib is a tyrosine kinase inhibitor active against ALK, MET, and ROS1.	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	83-87
23585220-9	2013	Levels of albumin and SHBG (which both bind testosterone) declined rapidly with crizotinib, but so did FSH, LH, and free testosterone, suggesting a centrally mediated, true hypogonadal effect.	Crizotinib	80-90	sex hormone binding globulin	Homo sapiens	22-26
24649213-5	2013	Echinoderm microtubule-like protein 4-anaplastic lymphoma kinase (EML4-ALK) translocation is another alteration capable of predicting the efficacy of anti-ALK agents, such as crizotinib.	Crizotinib	175-185	ALK receptor tyrosine kinase	Homo sapiens	71-74
24649213-5	2013	Echinoderm microtubule-like protein 4-anaplastic lymphoma kinase (EML4-ALK) translocation is another alteration capable of predicting the efficacy of anti-ALK agents, such as crizotinib.	Crizotinib	175-185	ALK receptor tyrosine kinase	Homo sapiens	155-158
23811600-5	2013	Demonstrating the value of the assay, we identify ETV6-NTRK3 as a target of the FDA-approved drug crizotinib (Xalkori).	Crizotinib	98-108	ets variant 6	Mus musculus	50-54
23811600-5	2013	Demonstrating the value of the assay, we identify ETV6-NTRK3 as a target of the FDA-approved drug crizotinib (Xalkori).	Crizotinib	98-108	neurotrophic tyrosine kinase, receptor, type 3	Mus musculus	55-60
23811600-6	2013	Crizotinib inhibits proliferation of ETV6-NTRK3-dependent tumor cells with nanomolar potency and induces the regression of established tumor xenografts in mice.	Crizotinib	0-10	ets variant 6	Mus musculus	37-41
23811600-6	2013	Crizotinib inhibits proliferation of ETV6-NTRK3-dependent tumor cells with nanomolar potency and induces the regression of established tumor xenografts in mice.	Crizotinib	0-10	neurotrophic tyrosine kinase, receptor, type 3	Mus musculus	42-47
23615728-2	2013	Crizotinib (PF-02341066) is identified as an ATP competitive small-molecular inhibitor for anaplastic lymphoma kinase (ALK).	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	91-117
23615728-2	2013	Crizotinib (PF-02341066) is identified as an ATP competitive small-molecular inhibitor for anaplastic lymphoma kinase (ALK).	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	119-122
23615728-2	2013	Crizotinib (PF-02341066) is identified as an ATP competitive small-molecular inhibitor for anaplastic lymphoma kinase (ALK).	Crizotinib	12-23	anaplastic lymphoma kinase	Mus musculus	91-117
23615728-2	2013	Crizotinib (PF-02341066) is identified as an ATP competitive small-molecular inhibitor for anaplastic lymphoma kinase (ALK).	Crizotinib	12-23	anaplastic lymphoma kinase	Mus musculus	119-122
23615728-3	2013	The US Food and Drug Administration (FDA) approved crizotinib to be used for the treatment of patients with locally advanced or metastatic ALK-positive NSCLC in 2011.	Crizotinib	51-61	ALK receptor tyrosine kinase	Homo sapiens	139-142
23615728-11	2013	In these assays, crizotinib was found to dock into Smad3 and activate the Smad signaling pathway.	Crizotinib	17-27	SMAD family member 3	Mus musculus	51-56
23669222-1	2013	PURPOSE: The diagnostic test for ALK rearrangement in non-small-cell lung cancer (NSCLC) for crizotinib treatment is currently done on tumor biopsies or fine-needle aspirations.	Crizotinib	93-103	ALK receptor tyrosine kinase	Homo sapiens	33-36
23669222-6	2013	ALK-rearranged CTCs were monitored in five patients treated with crizotinib.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	0-3
23669222-11	2013	Variations in ALK-rearranged CTC levels were detected in patients being treated with crizotinib.	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	14-17
23669222-12	2013	CONCLUSION: ALK rearrangement can be detected in CTCs of patients with ALK-positive NSCLC by using a filtration technique and FA-FISH, enabling both diagnostic testing and monitoring of crizotinib treatment.	Crizotinib	186-196	ALK receptor tyrosine kinase	Homo sapiens	12-15
23669222-12	2013	CONCLUSION: ALK rearrangement can be detected in CTCs of patients with ALK-positive NSCLC by using a filtration technique and FA-FISH, enabling both diagnostic testing and monitoring of crizotinib treatment.	Crizotinib	186-196	ALK receptor tyrosine kinase	Homo sapiens	71-74
23724913-0	2013	Crizotinib versus chemotherapy in advanced ALK-positive lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	43-46
23724913-1	2013	BACKGROUND: In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK.	Crizotinib	164-174	ALK receptor tyrosine kinase	Homo sapiens	71-102
23724913-1	2013	BACKGROUND: In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK.	Crizotinib	164-174	ALK receptor tyrosine kinase	Homo sapiens	104-107
23724913-1	2013	BACKGROUND: In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK.	Crizotinib	164-174	ALK receptor tyrosine kinase	Homo sapiens	220-223
23724913-12	2013	CONCLUSIONS: Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	139-142
23724914-0	2013	Acquired resistance to crizotinib from a mutation in CD74-ROS1.	Crizotinib	23-33	CD74 molecule	Homo sapiens	53-57
23724914-0	2013	Acquired resistance to crizotinib from a mutation in CD74-ROS1.	Crizotinib	23-33	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	58-62
23724914-1	2013	Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), has also recently shown efficacy in the treatment of lung cancers with ROS1 translocations.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	28-54
23724914-1	2013	Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), has also recently shown efficacy in the treatment of lung cancers with ROS1 translocations.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	56-59
23724914-1	2013	Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), has also recently shown efficacy in the treatment of lung cancers with ROS1 translocations.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	133-137
23724914-2	2013	Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74-ROS1 rearrangement who had initially shown a dramatic response to treatment.	Crizotinib	14-24	CD74 molecule	Homo sapiens	96-100
23724914-2	2013	Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74-ROS1 rearrangement who had initially shown a dramatic response to treatment.	Crizotinib	14-24	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	101-105
23785245-5	2013	Crizotinib, the first clinically available ALK tyrosine kinase inhibitor, appeared more effective compared with standard chemotherapy in NSCLC patients harboring EML4-ALK.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	43-46
23785245-5	2013	Crizotinib, the first clinically available ALK tyrosine kinase inhibitor, appeared more effective compared with standard chemotherapy in NSCLC patients harboring EML4-ALK.	Crizotinib	0-10	EMAP like 4	Homo sapiens	162-166
23785245-5	2013	Crizotinib, the first clinically available ALK tyrosine kinase inhibitor, appeared more effective compared with standard chemotherapy in NSCLC patients harboring EML4-ALK.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	167-170
23686600-2	2013	SUMMARY: Crizotinib (Xalkori, Pfizer Inc.) is a novel tyrosine kinase inhibitor approved for the treatment of patients with locally advanced or metastatic NSCLC who exhibit assay-confirmed mutations of the gene coding for anaplastic lymphoma kinase (ALK).	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	222-248
23686600-2	2013	SUMMARY: Crizotinib (Xalkori, Pfizer Inc.) is a novel tyrosine kinase inhibitor approved for the treatment of patients with locally advanced or metastatic NSCLC who exhibit assay-confirmed mutations of the gene coding for anaplastic lymphoma kinase (ALK).	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	250-253
23686600-3	2013	The primary biochemical mechanism of crizotinib is to inhibit ALK expression, leading to increased cell proliferation and decreased apoptosis.	Crizotinib	37-47	ALK receptor tyrosine kinase	Homo sapiens	62-65
23686600-4	2013	Crizotinib is metabolized and excreted after O-dealkylation by cytochrome P-450 (CYP) isoenzyme 3A4/5; as crizotinib is also an inhibitor of CYP3A4/5, its use entails a high potential for drug interactions, including confirmed interactions with ketoconazole and rifampin that can alter crizotinib pharmacokinetics.	Crizotinib	0-10	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	141-147
23686600-4	2013	Crizotinib is metabolized and excreted after O-dealkylation by cytochrome P-450 (CYP) isoenzyme 3A4/5; as crizotinib is also an inhibitor of CYP3A4/5, its use entails a high potential for drug interactions, including confirmed interactions with ketoconazole and rifampin that can alter crizotinib pharmacokinetics.	Crizotinib	106-116	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	141-147
23686600-5	2013	A Phase I trial involving patients with ALK gene mutation-positive NSCLC demonstrated significant disease control with oral crizotinib use, including an overall eight-week response rate of 87% and an estimated six-month survival of 72%.	Crizotinib	124-134	ALK receptor tyrosine kinase	Homo sapiens	40-43
23686600-9	2013	CONCLUSION: Crizotinib appears to be efficacious and well tolerated in patients with NSCLC and may have future potential applications in treating lymphomas and other cancers driven by ALK or c-MET gene mutations.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	184-187
23686600-9	2013	CONCLUSION: Crizotinib appears to be efficacious and well tolerated in patients with NSCLC and may have future potential applications in treating lymphomas and other cancers driven by ALK or c-MET gene mutations.	Crizotinib	12-22	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	191-196
23733083-4	2013	CONCLUSION: EGFR activating mutations (exons 18 to 21) and EML4-ALK rearrangement are clinically important markers able to select NSCLC patients which benefit from EGFR or ALK tyrosine kinase inhibitors (gefitinib, erlotinib, crizotinib).	Crizotinib	226-236	epidermal growth factor receptor	Homo sapiens	12-16
23733083-4	2013	CONCLUSION: EGFR activating mutations (exons 18 to 21) and EML4-ALK rearrangement are clinically important markers able to select NSCLC patients which benefit from EGFR or ALK tyrosine kinase inhibitors (gefitinib, erlotinib, crizotinib).	Crizotinib	226-236	EMAP like 4	Homo sapiens	59-63
23733083-4	2013	CONCLUSION: EGFR activating mutations (exons 18 to 21) and EML4-ALK rearrangement are clinically important markers able to select NSCLC patients which benefit from EGFR or ALK tyrosine kinase inhibitors (gefitinib, erlotinib, crizotinib).	Crizotinib	226-236	epidermal growth factor receptor	Homo sapiens	164-168
23733083-4	2013	CONCLUSION: EGFR activating mutations (exons 18 to 21) and EML4-ALK rearrangement are clinically important markers able to select NSCLC patients which benefit from EGFR or ALK tyrosine kinase inhibitors (gefitinib, erlotinib, crizotinib).	Crizotinib	226-236	ALK receptor tyrosine kinase	Homo sapiens	172-175
23505007-1	2013	BACKGROUND: Crizotinib is used for the treatment of advanced anaplastic lymphoma kinase (ALK)-rearranged nonsmall cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	61-87
23505007-1	2013	BACKGROUND: Crizotinib is used for the treatment of advanced anaplastic lymphoma kinase (ALK)-rearranged nonsmall cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	89-92
23553849-8	2013	Four patients (4%) achieved partial response (PR); all had disease that harbored anaplastic lymphoma kinase (ALK) gene rearrangement, retrospectively detected by FISH (n = 1) or PCR-based assays (n = 3), in crizotinib-naive patients enrolled to cohort C. Eight patients (8.1%) experienced treatment-related serious adverse events (AE); 2 of these (cardiac arrest and renal failure) resulted in death.	Crizotinib	207-217	ALK receptor tyrosine kinase	Homo sapiens	81-107
23707608-6	2013	Crizotinib, an ALK/MET inhibitor, led to increased ROS production, caspase activation, cholesterol accumulation, disruption in cardiac cell beat rate, and blockage of ion channels.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	15-18
23729361-13	2013	This lack of overlap was also observed in ALK-positive cancers with acquired resistance to crizotinib.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	42-45
23911227-9	2013	This approach has been successfully employed in the clinical approval of crizotinib for the treatment of ALK-rearranged non-small cell lung cancer.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	105-108
23857406-0	2013	Transformation to sarcomatoid carcinoma in ALK-rearranged adenocarcinoma, which developed acquired resistance to crizotinib and received subsequent chemotherapies.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	43-46
23664446-8	2013	Crizotinib, the ALK tyrosine kinase inhibitor, is highly effective in ALK-rearranged NSCLC; therefore, it may be imperative to identify all NSCLC that harbor ALK translocations in the near future.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	16-19
23664446-8	2013	Crizotinib, the ALK tyrosine kinase inhibitor, is highly effective in ALK-rearranged NSCLC; therefore, it may be imperative to identify all NSCLC that harbor ALK translocations in the near future.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	70-73
23664446-8	2013	Crizotinib, the ALK tyrosine kinase inhibitor, is highly effective in ALK-rearranged NSCLC; therefore, it may be imperative to identify all NSCLC that harbor ALK translocations in the near future.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	70-73
24070465-11	2013	Elderly patients affected by NSCLC harboring the EML4-ALK translocation could benefit mostly from a treatment with an oral inhibitor of such a rearrangement (crizotinib).	Crizotinib	158-168	EMAP like 4	Homo sapiens	49-53
24070465-11	2013	Elderly patients affected by NSCLC harboring the EML4-ALK translocation could benefit mostly from a treatment with an oral inhibitor of such a rearrangement (crizotinib).	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	54-57
23558310-0	2013	Complete metabolic response in a patient with repeatedly relapsed non-small cell lung cancer harboring ROS1 gene rearrangement after treatment with crizotinib.	Crizotinib	148-158	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	103-107
23769207-1	2013	The recent approval of crizotinib for the treatment of anaplastic lymphoma kinase (ALK)-rearranged advanced non-small cell lung cancer (NSCLC) in the US and other countries has provoked intense interest in ALK rearrangements as oncogenic drivers, and promises to revolutionise the way in which NSCLC is diagnosed and treated.	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	83-86
23769348-2	2013	After epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs), crizotinib targeted at EML4-ALK fusion gene becomes a significant drug of molecular targeted therapy in NSCLC.	Crizotinib	78-88	EMAP like 4	Homo sapiens	101-105
23819947-9	2013	This approach has been successfully employed in the clinical approval of crizotinib for the treatment of ALK-rearranged non-small cell lung cancer.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	105-108
23639470-1	2013	BACKGROUND: Currently, crizotinib is the only drug that has been approved for treatment of ALK-rearranged non-small-cell lung cancer (NSCLC).	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	91-94
23608109-4	2013	Few targets like epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements have successfully been targeted with EGFR tyrosine kinase inhibitors (TKIs) and crizotinib, respectively.	Crizotinib	204-214	epidermal growth factor receptor	Homo sapiens	17-49
23608109-4	2013	Few targets like epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements have successfully been targeted with EGFR tyrosine kinase inhibitors (TKIs) and crizotinib, respectively.	Crizotinib	204-214	epidermal growth factor receptor	Homo sapiens	51-55
23608109-4	2013	Few targets like epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements have successfully been targeted with EGFR tyrosine kinase inhibitors (TKIs) and crizotinib, respectively.	Crizotinib	204-214	ALK receptor tyrosine kinase	Homo sapiens	71-97
23608109-4	2013	Few targets like epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements have successfully been targeted with EGFR tyrosine kinase inhibitors (TKIs) and crizotinib, respectively.	Crizotinib	204-214	ALK receptor tyrosine kinase	Homo sapiens	99-102
23741400-1	2013	Patients with ALK gene rearrangements often manifest dramatic responses to crizotinib, an ALK inhibitor.	Crizotinib	75-85	ALK receptor tyrosine kinase	Homo sapiens	14-17
23741400-1	2013	Patients with ALK gene rearrangements often manifest dramatic responses to crizotinib, an ALK inhibitor.	Crizotinib	75-85	ALK receptor tyrosine kinase	Homo sapiens	90-93
23769348-2	2013	After epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs), crizotinib targeted at EML4-ALK fusion gene becomes a significant drug of molecular targeted therapy in NSCLC.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	106-109
23769348-3	2013	Phase I and II clinical trials prove that crizotinib is effective for treatment of activating EML4-ALK mutation in advanced NSCLC patients, little side-effect, and well tolerated.	Crizotinib	42-52	EMAP like 4	Homo sapiens	94-98
23769348-3	2013	Phase I and II clinical trials prove that crizotinib is effective for treatment of activating EML4-ALK mutation in advanced NSCLC patients, little side-effect, and well tolerated.	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	99-102
23769348-4	2013	Recently, crizotinib can inhibit ROS1 receptor tyrosine kinase and show extraordinary significant antitumor activity in ROS1-rearranged NSCLC.	Crizotinib	10-20	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	33-37
23769348-4	2013	Recently, crizotinib can inhibit ROS1 receptor tyrosine kinase and show extraordinary significant antitumor activity in ROS1-rearranged NSCLC.	Crizotinib	10-20	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	120-124
23617353-0	2013	Testing for anaplastic lymphoma kinase rearrangement to target crizotinib therapy: oncology, pathology and health economic perspectives.	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	12-38
23598276-7	2013	As expected, other c-MET inhibitors, crizotinib and PHA-665752, suppressed the growth of c-MET-addicted cancers, but not the growth of cancers that are not addicted to c-MET.	Crizotinib	37-47	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	19-24
23598276-7	2013	As expected, other c-MET inhibitors, crizotinib and PHA-665752, suppressed the growth of c-MET-addicted cancers, but not the growth of cancers that are not addicted to c-MET.	Crizotinib	37-47	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	89-94
23598276-7	2013	As expected, other c-MET inhibitors, crizotinib and PHA-665752, suppressed the growth of c-MET-addicted cancers, but not the growth of cancers that are not addicted to c-MET.	Crizotinib	37-47	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	89-94
23400546-2	2013	One of these RTKs, c-ros oncogene 1, receptor tyrosine kinase (ROS1), has been identified as a driver mutation in NSCLC, because its inhibition by crizotinib, an anaplastic lymphoma receptor tyrosine kinase (ALK)/met proto-oncogene hepatocyte growth factor receptor (MET)/ROS1 inhibitor, led to significant tumor shrinkage in ROS1-rearranged NSCLC.	Crizotinib	147-157	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	19-61
23400546-2	2013	One of these RTKs, c-ros oncogene 1, receptor tyrosine kinase (ROS1), has been identified as a driver mutation in NSCLC, because its inhibition by crizotinib, an anaplastic lymphoma receptor tyrosine kinase (ALK)/met proto-oncogene hepatocyte growth factor receptor (MET)/ROS1 inhibitor, led to significant tumor shrinkage in ROS1-rearranged NSCLC.	Crizotinib	147-157	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	63-67
23400546-2	2013	One of these RTKs, c-ros oncogene 1, receptor tyrosine kinase (ROS1), has been identified as a driver mutation in NSCLC, because its inhibition by crizotinib, an anaplastic lymphoma receptor tyrosine kinase (ALK)/met proto-oncogene hepatocyte growth factor receptor (MET)/ROS1 inhibitor, led to significant tumor shrinkage in ROS1-rearranged NSCLC.	Crizotinib	147-157	ALK receptor tyrosine kinase	Homo sapiens	162-206
23400546-2	2013	One of these RTKs, c-ros oncogene 1, receptor tyrosine kinase (ROS1), has been identified as a driver mutation in NSCLC, because its inhibition by crizotinib, an anaplastic lymphoma receptor tyrosine kinase (ALK)/met proto-oncogene hepatocyte growth factor receptor (MET)/ROS1 inhibitor, led to significant tumor shrinkage in ROS1-rearranged NSCLC.	Crizotinib	147-157	ALK receptor tyrosine kinase	Homo sapiens	208-211
23400546-2	2013	One of these RTKs, c-ros oncogene 1, receptor tyrosine kinase (ROS1), has been identified as a driver mutation in NSCLC, because its inhibition by crizotinib, an anaplastic lymphoma receptor tyrosine kinase (ALK)/met proto-oncogene hepatocyte growth factor receptor (MET)/ROS1 inhibitor, led to significant tumor shrinkage in ROS1-rearranged NSCLC.	Crizotinib	147-157	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	272-276
23400546-2	2013	One of these RTKs, c-ros oncogene 1, receptor tyrosine kinase (ROS1), has been identified as a driver mutation in NSCLC, because its inhibition by crizotinib, an anaplastic lymphoma receptor tyrosine kinase (ALK)/met proto-oncogene hepatocyte growth factor receptor (MET)/ROS1 inhibitor, led to significant tumor shrinkage in ROS1-rearranged NSCLC.	Crizotinib	147-157	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	272-276
23617353-1	2013	Crizotinib is a first-in-class oral anaplastic lymphoma kinase (ALK) inhibitor targeting ALK-rearranged non-small-cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	36-62
23617353-1	2013	Crizotinib is a first-in-class oral anaplastic lymphoma kinase (ALK) inhibitor targeting ALK-rearranged non-small-cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	64-67
23617353-1	2013	Crizotinib is a first-in-class oral anaplastic lymphoma kinase (ALK) inhibitor targeting ALK-rearranged non-small-cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	89-92
23449277-1	2013	INTRODUCTION: Oncogenic ALK kinase activity associated with ALK gene rearrangement is the target of crizotinib, an ALK inhibitor recently approved by the Food and Drug Administration for the treatment of ALK-rearranged (ALK+) non-small cell lung cancers.	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	24-27
23449277-1	2013	INTRODUCTION: Oncogenic ALK kinase activity associated with ALK gene rearrangement is the target of crizotinib, an ALK inhibitor recently approved by the Food and Drug Administration for the treatment of ALK-rearranged (ALK+) non-small cell lung cancers.	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	60-63
23449277-1	2013	INTRODUCTION: Oncogenic ALK kinase activity associated with ALK gene rearrangement is the target of crizotinib, an ALK inhibitor recently approved by the Food and Drug Administration for the treatment of ALK-rearranged (ALK+) non-small cell lung cancers.	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	60-63
23449277-1	2013	INTRODUCTION: Oncogenic ALK kinase activity associated with ALK gene rearrangement is the target of crizotinib, an ALK inhibitor recently approved by the Food and Drug Administration for the treatment of ALK-rearranged (ALK+) non-small cell lung cancers.	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	60-63
23449277-1	2013	INTRODUCTION: Oncogenic ALK kinase activity associated with ALK gene rearrangement is the target of crizotinib, an ALK inhibitor recently approved by the Food and Drug Administration for the treatment of ALK-rearranged (ALK+) non-small cell lung cancers.	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	60-63
23584297-0	2013	Clinical impact of continued crizotinib administration after isolated central nervous system progression in patients with lung cancer positive for ALK rearrangement.	Crizotinib	29-39	ALK receptor tyrosine kinase	Homo sapiens	147-150
23427294-2	2013	Crizotinib (PF02341066) is a dual MET and ALK inhibitor and approved for the treatment of a subset of non-small cell lung carcinoma and in clinical development for other malignancies.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	42-45
23427294-2	2013	Crizotinib (PF02341066) is a dual MET and ALK inhibitor and approved for the treatment of a subset of non-small cell lung carcinoma and in clinical development for other malignancies.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	42-45
23427294-10	2013	These results establish a critical role of PUMA in mediating apoptotic responses of colon cancer cells to crizotinib and suggest that mechanisms of oncogenic addiction to MET/ALK-mediated survival may be cell type-specific.	Crizotinib	106-116	ALK receptor tyrosine kinase	Homo sapiens	175-178
23584297-4	2013	METHODS: We retrospectively evaluated the continuation of crizotinib treatment after radiotherapy for isolated CNS progression in ALK-rearrangement-positive non-small-cell lung cancer patients.	Crizotinib	58-68	ALK receptor tyrosine kinase	Homo sapiens	130-133
23617826-0	2013	Early pneumothorax as a feature of response to crizotinib therapy in a patient with ALK rearranged lung adenocarcinoma.	Crizotinib	47-57	ALK receptor tyrosine kinase	Homo sapiens	84-87
23617826-1	2013	BACKGROUND: Single arm phase 1 and 2 studies on Crizotinib in ALK-positive patients so far have shown rapid and durable responses.	Crizotinib	48-58	ALK receptor tyrosine kinase	Homo sapiens	62-65
23280244-2	2013	Crizotinib, a tyrosine kinase inhibitor with significant activity against ALK, has demonstrated high response rates and prolonged progression-free survival in ALK-positive patients enrolled in phase 1/2 clinical trials.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	74-77
23443800-0	2013	ALK inhibitor PF02341066 (crizotinib) increases sensitivity to radiation in non-small cell lung cancer expressing EML4-ALK.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	0-3
23443800-0	2013	ALK inhibitor PF02341066 (crizotinib) increases sensitivity to radiation in non-small cell lung cancer expressing EML4-ALK.	Crizotinib	26-36	EMAP like 4	Homo sapiens	114-118
23443800-0	2013	ALK inhibitor PF02341066 (crizotinib) increases sensitivity to radiation in non-small cell lung cancer expressing EML4-ALK.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	119-122
23443800-1	2013	Crizotinib (PF02341066) is a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that has been shown to selectively inhibit growth of cancer cells that harbor the EML4-ALK fusion found in a subset of patients with non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	58-84
23443800-1	2013	Crizotinib (PF02341066) is a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that has been shown to selectively inhibit growth of cancer cells that harbor the EML4-ALK fusion found in a subset of patients with non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	86-89
23443800-1	2013	Crizotinib (PF02341066) is a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that has been shown to selectively inhibit growth of cancer cells that harbor the EML4-ALK fusion found in a subset of patients with non-small cell lung cancer (NSCLC).	Crizotinib	0-10	EMAP like 4	Homo sapiens	173-177
23443800-1	2013	Crizotinib (PF02341066) is a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that has been shown to selectively inhibit growth of cancer cells that harbor the EML4-ALK fusion found in a subset of patients with non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	178-181
23443800-1	2013	Crizotinib (PF02341066) is a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that has been shown to selectively inhibit growth of cancer cells that harbor the EML4-ALK fusion found in a subset of patients with non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	58-84
23443800-1	2013	Crizotinib (PF02341066) is a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that has been shown to selectively inhibit growth of cancer cells that harbor the EML4-ALK fusion found in a subset of patients with non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	86-89
23443800-1	2013	Crizotinib (PF02341066) is a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that has been shown to selectively inhibit growth of cancer cells that harbor the EML4-ALK fusion found in a subset of patients with non-small cell lung cancer (NSCLC).	Crizotinib	12-22	EMAP like 4	Homo sapiens	173-177
23443800-1	2013	Crizotinib (PF02341066) is a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that has been shown to selectively inhibit growth of cancer cells that harbor the EML4-ALK fusion found in a subset of patients with non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	178-181
23250669-4	2013	This paper summarizes an anticancer drug case study describing the translational PKPD modeling of crizotinib, an orally available, potent small molecule inhibitor of multiple tyrosine kinases including anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition factor (MET), from nonclinical to clinical development.	Crizotinib	98-108	ALK receptor tyrosine kinase	Homo sapiens	202-228
23250669-4	2013	This paper summarizes an anticancer drug case study describing the translational PKPD modeling of crizotinib, an orally available, potent small molecule inhibitor of multiple tyrosine kinases including anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition factor (MET), from nonclinical to clinical development.	Crizotinib	98-108	ALK receptor tyrosine kinase	Homo sapiens	230-233
23250669-7	2013	These simulation results of crizotinib-mediated ALK and MET inhibition appeared consistent with the currently reported clinical responses.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	48-51
23280244-2	2013	Crizotinib, a tyrosine kinase inhibitor with significant activity against ALK, has demonstrated high response rates and prolonged progression-free survival in ALK-positive patients enrolled in phase 1/2 clinical trials.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	159-162
23280244-3	2013	In 2011, crizotinib received accelerated approval from the US Food and Drug Administration (FDA) for the treatment of proven ALK-positive NSCLC using an FDA-approved diagnostic test.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	125-128
23134735-8	2013	We identified a novel MEKK2 inhibitor and confirmed that crizotinib and bosutinib are potent in vitro inhibitors of MEKK2 activity with IC50 values of <100 nM.	Crizotinib	57-67	mitogen-activated protein kinase kinase kinase 2	Homo sapiens	22-27
23472711-4	2013	AREAS COVERED: In this article, updated data derived from the development and the use of crizotinib (the most advanced in development among tyrosine kinase ALK inhibitors) in comparison with standard second-line chemotherapy for patients affected by ALK-altered NSCLC are reviewed.	Crizotinib	89-99	ALK receptor tyrosine kinase	Homo sapiens	156-159
23472711-4	2013	AREAS COVERED: In this article, updated data derived from the development and the use of crizotinib (the most advanced in development among tyrosine kinase ALK inhibitors) in comparison with standard second-line chemotherapy for patients affected by ALK-altered NSCLC are reviewed.	Crizotinib	89-99	ALK receptor tyrosine kinase	Homo sapiens	250-253
23134735-8	2013	We identified a novel MEKK2 inhibitor and confirmed that crizotinib and bosutinib are potent in vitro inhibitors of MEKK2 activity with IC50 values of <100 nM.	Crizotinib	57-67	mitogen-activated protein kinase kinase kinase 2	Homo sapiens	116-121
23486271-0	2013	Rapid response of brain metastasis to crizotinib in a patient with ALK rearrangement-positive non-small-cell lung cancer.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	67-70
23584342-0	2013	A patient with anaplastic lymphoma kinase-positive non-small cell lung cancer with development of leptomeningeal carcinomatosis while on targeted treatment with crizotinib.	Crizotinib	161-171	ALK receptor tyrosine kinase	Homo sapiens	15-41
23584342-5	2013	This case report summarizes the management of a patient with ALK-positive NSCLC who developed LM while on targeted treatment with crizotinib within the context of current NCCN Clinical Practice Guidelines in Oncology and recently published studies.	Crizotinib	130-140	ALK receptor tyrosine kinase	Homo sapiens	61-64
23344087-0	2013	Heterogeneity of genetic changes associated with acquired crizotinib resistance in ALK-rearranged lung cancer.	Crizotinib	58-68	ALK receptor tyrosine kinase	Homo sapiens	83-86
23344087-1	2013	BACKGROUND: Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is markedly sensitive to the ALK inhibitor crizotinib.	Crizotinib	134-144	ALK receptor tyrosine kinase	Homo sapiens	12-38
23344087-1	2013	BACKGROUND: Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is markedly sensitive to the ALK inhibitor crizotinib.	Crizotinib	134-144	ALK receptor tyrosine kinase	Homo sapiens	40-43
23576200-4	2013	Clinical data have been generated for crizotinib, a small molecule inhibitor of the ALK receptor tyrosine kinase, demonstrating a substantial improvement of objective response rate and prolonged progression-free survival (PFS) compared to standard chemotherapy in pretreated NSCLC patients harbouring EML4-ALK fusion genes.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	84-87
23344087-1	2013	BACKGROUND: Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is markedly sensitive to the ALK inhibitor crizotinib.	Crizotinib	134-144	ALK receptor tyrosine kinase	Homo sapiens	120-123
23344087-6	2013	RESULTS: After a median duration of 6 months (range, 4-12 months), seven ALK-positive NSCLC patients developed acquired resistance to crizotinib.	Crizotinib	134-144	ALK receptor tyrosine kinase	Homo sapiens	73-76
23344087-8	2013	Of note, one patient displayed ALK gene copy number gain (4.1-fold increase compared with the pre-crizotinib specimen) and EGFR L858R mutation with high polysomy.	Crizotinib	98-108	ALK receptor tyrosine kinase	Homo sapiens	31-34
23344087-12	2013	CONCLUSIONS: Genetic changes associated with crizotinib resistance are heterogeneous in ALK-rearranged NSCLC patients who respond to crizotinib and subsequently develop resistance.	Crizotinib	45-55	ALK receptor tyrosine kinase	Homo sapiens	88-91
23344087-12	2013	CONCLUSIONS: Genetic changes associated with crizotinib resistance are heterogeneous in ALK-rearranged NSCLC patients who respond to crizotinib and subsequently develop resistance.	Crizotinib	133-143	ALK receptor tyrosine kinase	Homo sapiens	88-91
23561899-0	2013	[Crizotinib: a targeted therapy in advanced ALK-positive non-small cell lung cancer].	Crizotinib	1-11	ALK receptor tyrosine kinase	Homo sapiens	44-47
23561899-1	2013	Crizotinib is a small orally-administered ALK inhibitor for patients with non-small cell lung cancer with EML4-ALK rearrangement (echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	42-45
23561899-1	2013	Crizotinib is a small orally-administered ALK inhibitor for patients with non-small cell lung cancer with EML4-ALK rearrangement (echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase).	Crizotinib	0-10	EMAP like 4	Homo sapiens	106-110
23561899-1	2013	Crizotinib is a small orally-administered ALK inhibitor for patients with non-small cell lung cancer with EML4-ALK rearrangement (echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	111-114
25806218-4	2013	Crizotinib, an orally available small molecule ATP-mimetic compound which was originally designed as a MET inhibitor, was recognized to have "off-target" anti-ALK activity and has been approved in the USA for the treatment of patients with ALK-positive NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	159-162
25806218-4	2013	Crizotinib, an orally available small molecule ATP-mimetic compound which was originally designed as a MET inhibitor, was recognized to have "off-target" anti-ALK activity and has been approved in the USA for the treatment of patients with ALK-positive NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	240-243
25806222-4	2013	In addition, the MET/ALK/ROS inhibitor crizotinib has already shown impressive clinical activity in patients with advanced ROS1-positive lung cancer.	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	21-24
23385859-4	2013	RECENT FINDINGS: Crizotinib is a tyrosine kinase inhibitor of MET, ALK and ROS1.	Crizotinib	17-27	ALK receptor tyrosine kinase	Homo sapiens	67-70
23385859-4	2013	RECENT FINDINGS: Crizotinib is a tyrosine kinase inhibitor of MET, ALK and ROS1.	Crizotinib	17-27	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	75-79
23507588-6	2013	Furthermore, in 2012, crizotinib was approved for lung cancer treatment with anaplastic lymphoma kinase(ALK)gene translocation.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	104-107
23533265-1	2013	UNLABELLED: EML4-ALK gene rearrangements define a unique subset of patients with non-small cell lung carcinoma (NSCLC), and the clinical success of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib in this population has become a paradigm for molecularly targeted therapy.	Crizotinib	195-205	EMAP like 4	Homo sapiens	12-16
23533265-1	2013	UNLABELLED: EML4-ALK gene rearrangements define a unique subset of patients with non-small cell lung carcinoma (NSCLC), and the clinical success of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib in this population has become a paradigm for molecularly targeted therapy.	Crizotinib	195-205	ALK receptor tyrosine kinase	Homo sapiens	17-20
23533265-1	2013	UNLABELLED: EML4-ALK gene rearrangements define a unique subset of patients with non-small cell lung carcinoma (NSCLC), and the clinical success of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib in this population has become a paradigm for molecularly targeted therapy.	Crizotinib	195-205	ALK receptor tyrosine kinase	Homo sapiens	152-178
23533265-1	2013	UNLABELLED: EML4-ALK gene rearrangements define a unique subset of patients with non-small cell lung carcinoma (NSCLC), and the clinical success of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib in this population has become a paradigm for molecularly targeted therapy.	Crizotinib	195-205	ALK receptor tyrosine kinase	Homo sapiens	180-183
23533265-2	2013	Here, we show that the Hsp90 inhibitor ganetespib induced loss of EML4-ALK expression and depletion of multiple oncogenic signaling proteins in ALK-driven NSCLC cells, leading to greater in vitro potency, superior antitumor efficacy, and prolonged animal survival compared with results obtained with crizotinib.	Crizotinib	300-310	heat shock protein 90 alpha family class A member 1	Homo sapiens	23-28
24455567-2	2013	ALK-positivity confers sensitivity to small-molecule ALK kinase inhibitors, such as crizotinib.	Crizotinib	84-94	ALK receptor tyrosine kinase	Homo sapiens	0-3
24455567-2	2013	ALK-positivity confers sensitivity to small-molecule ALK kinase inhibitors, such as crizotinib.	Crizotinib	84-94	ALK receptor tyrosine kinase	Homo sapiens	53-56
24455567-4	2013	Phase I and II studies of crizotinib in ALK-positive lung cancer have demonstrated significant activity and impressive clinical benefit, which led to its early approval by USFDA in 2011.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	40-43
23401436-2	2013	ALK-positive cancers are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	0-3
23401436-2	2013	ALK-positive cancers are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	60-63
23401436-3	2013	Phase I and II studies of crizotinib in ALK-positive lung cancer demonstrated impressive activity and clinical benefit, leading to rapid US Food and Drug Administration approval in 2011.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	40-43
23104988-9	2013	Irrespective of the nature of the observed ALK mutants, in every case the activity of the mutant ALK receptors could be abrogated by the ALK inhibitor crizotinib (Xalkori/PF-02341066), albeit with differing levels of sensitivity.	Crizotinib	151-161	Anaplastic lymphoma kinase	Drosophila melanogaster	43-46
23104988-9	2013	Irrespective of the nature of the observed ALK mutants, in every case the activity of the mutant ALK receptors could be abrogated by the ALK inhibitor crizotinib (Xalkori/PF-02341066), albeit with differing levels of sensitivity.	Crizotinib	151-161	Anaplastic lymphoma kinase	Drosophila melanogaster	97-100
23104988-9	2013	Irrespective of the nature of the observed ALK mutants, in every case the activity of the mutant ALK receptors could be abrogated by the ALK inhibitor crizotinib (Xalkori/PF-02341066), albeit with differing levels of sensitivity.	Crizotinib	151-161	Anaplastic lymphoma kinase	Drosophila melanogaster	97-100
23407563-0	2013	Esophagitis: a novel adverse event of crizotinib in a patient with ALK-positive non-small-cell lung cancer.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	67-70
23576200-4	2013	Clinical data have been generated for crizotinib, a small molecule inhibitor of the ALK receptor tyrosine kinase, demonstrating a substantial improvement of objective response rate and prolonged progression-free survival (PFS) compared to standard chemotherapy in pretreated NSCLC patients harbouring EML4-ALK fusion genes.	Crizotinib	38-48	EMAP like 4	Homo sapiens	301-305
23407559-1	2013	INTRODUCTION: Recent clinical trials led to the approval of crizotinib (PF-02341066; Pfizer) by the U.S. Food and Drug Administration for the treatment of locally advanced or metastatic non-small-cell lung cancer (NSCLC) patients whose tumors are positive for anaplastic lymphoma kinase (ALK) alterations.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	260-286
23576200-4	2013	Clinical data have been generated for crizotinib, a small molecule inhibitor of the ALK receptor tyrosine kinase, demonstrating a substantial improvement of objective response rate and prolonged progression-free survival (PFS) compared to standard chemotherapy in pretreated NSCLC patients harbouring EML4-ALK fusion genes.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	306-309
23407559-1	2013	INTRODUCTION: Recent clinical trials led to the approval of crizotinib (PF-02341066; Pfizer) by the U.S. Food and Drug Administration for the treatment of locally advanced or metastatic non-small-cell lung cancer (NSCLC) patients whose tumors are positive for anaplastic lymphoma kinase (ALK) alterations.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	288-291
23561259-0	2013	Crizotinib administered via nasogastric and percutaneous endoscopic gastrostomy tubes for the successful treatment of ALK-rearranged lung cancer in a patient with poor performance status.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	118-121
23561259-1	2013	Crizotinib-an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor-is effective in non-small-cell lung cancers (NSCLCs) that express ALK.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	14-40
23561259-1	2013	Crizotinib-an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor-is effective in non-small-cell lung cancers (NSCLCs) that express ALK.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	42-45
23561259-1	2013	Crizotinib-an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor-is effective in non-small-cell lung cancers (NSCLCs) that express ALK.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	139-142
23561259-2	2013	Here, we report a patient with ALK-positive lung adenocarcinoma who was administered crizotinib via nasogastric and percutaneous endoscopic gastrostomy (PEG) tubes, with positive results.	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	31-34
23561259-3	2013	This case indicates that patients with ALK-positive NSCLC may successfully be treated with crizotinib via nasogastric or PEG tubes.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	39-42
23325296-5	2013	Crizotinib (PF-02341066) is an orally bioavailable, ATP-competitive, small molecule inhibitor of both the receptor tyrosine kinases ALK and c-MET (hepatocyte growth factor receptor).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	132-135
23254764-3	2013	PF-02341066 (crizotinib)             is a novel dual c-Met and EML4-ALK inhibitor, and preclinical studies have shown             that treatment with ALK inhibitors leads to drastic tumor regression in xenograft             models.	Crizotinib	13-23	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	53-58
23254764-3	2013	PF-02341066 (crizotinib)             is a novel dual c-Met and EML4-ALK inhibitor, and preclinical studies have shown             that treatment with ALK inhibitors leads to drastic tumor regression in xenograft             models.	Crizotinib	13-23	EMAP like 4	Homo sapiens	63-67
23325296-5	2013	Crizotinib (PF-02341066) is an orally bioavailable, ATP-competitive, small molecule inhibitor of both the receptor tyrosine kinases ALK and c-MET (hepatocyte growth factor receptor).	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	140-180
23254764-3	2013	PF-02341066 (crizotinib)             is a novel dual c-Met and EML4-ALK inhibitor, and preclinical studies have shown             that treatment with ALK inhibitors leads to drastic tumor regression in xenograft             models.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	68-71
23254764-3	2013	PF-02341066 (crizotinib)             is a novel dual c-Met and EML4-ALK inhibitor, and preclinical studies have shown             that treatment with ALK inhibitors leads to drastic tumor regression in xenograft             models.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	150-153
28609030-0	2013	Crizotinib -- Benefit Assessment According to  35a Social Code Book V The aim of this report is to assess the added benefit of crizotinib in patients with previously treated anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC): in whom chemotherapy is indicated (in particular, these can be patients with Eastern Cooperative Oncology Group [ECOG] performance status 0, 1, and, if applicable, 2), in comparison with chemotherapy (docetaxel/pemetrexed) as appropriate comparator therapy (ACT) (chemotherapy population).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	202-205
23325296-5	2013	Crizotinib (PF-02341066) is an orally bioavailable, ATP-competitive, small molecule inhibitor of both the receptor tyrosine kinases ALK and c-MET (hepatocyte growth factor receptor).	Crizotinib	12-23	ALK receptor tyrosine kinase	Homo sapiens	132-135
23325296-5	2013	Crizotinib (PF-02341066) is an orally bioavailable, ATP-competitive, small molecule inhibitor of both the receptor tyrosine kinases ALK and c-MET (hepatocyte growth factor receptor).	Crizotinib	12-23	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	140-180
23325296-6	2013	Crizotinib has been shown to yield important clinical benefit such as objective response rate, progression-free survival (PFS), and anticipated improvements in quality of life when used in pretreated patients with advanced NSCLC harboring EML4-ALK gene rearrangement.	Crizotinib	0-10	EMAP like 4	Homo sapiens	239-243
23325296-6	2013	Crizotinib has been shown to yield important clinical benefit such as objective response rate, progression-free survival (PFS), and anticipated improvements in quality of life when used in pretreated patients with advanced NSCLC harboring EML4-ALK gene rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	244-247
23325296-10	2013	Crizotinib is a new standard of care for patients with advanced, ALK-positive, NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	65-68
28609030-0	2013	Crizotinib -- Benefit Assessment According to  35a Social Code Book V The aim of this report is to assess the added benefit of crizotinib in patients with previously treated anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC): in whom chemotherapy is indicated (in particular, these can be patients with Eastern Cooperative Oncology Group [ECOG] performance status 0, 1, and, if applicable, 2), in comparison with chemotherapy (docetaxel/pemetrexed) as appropriate comparator therapy (ACT) (chemotherapy population).	Crizotinib	127-137	ALK receptor tyrosine kinase	Homo sapiens	174-200
28609030-0	2013	Crizotinib -- Benefit Assessment According to  35a Social Code Book V The aim of this report is to assess the added benefit of crizotinib in patients with previously treated anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC): in whom chemotherapy is indicated (in particular, these can be patients with Eastern Cooperative Oncology Group [ECOG] performance status 0, 1, and, if applicable, 2), in comparison with chemotherapy (docetaxel/pemetrexed) as appropriate comparator therapy (ACT) (chemotherapy population).	Crizotinib	127-137	ALK receptor tyrosine kinase	Homo sapiens	202-205
23129213-5	2013	Crizotinib E(max) and EC(50) for CYP3A4 induction (measured as mRNA expression) were estimated as 6.4- to 29-fold and 0.47 to 3.1 microM, respectively.	Crizotinib	0-10	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	33-39
23386065-0	2013	Crizotinib: a new treatment option for ALK-positive non-small cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	39-42
23386065-1	2013	OBJECTIVE: To review the characteristics and clinical trial data of crizotinib in ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	68-78	ALK receptor tyrosine kinase	Homo sapiens	82-85
23386065-3	2013	STUDY SELECTION/DATA EXTRACTION: Phase 1, 2, and 3 trials evaluating the safety and efficacy of crizotinib in a cohort of patients with ALK rearrangements and advanced NSCLC were evaluated.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	136-139
23386065-7	2013	Crizotinib is an oral selective inhibitor of ALK and mesenchymal epithelial growth factor tyrosine kinases.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	45-48
23386065-10	2013	Further clinical trial results confirmed improvement in response rates, duration of response, as well as progression-free survival in ALK-positive patients with NSCLC receiving crizotinib.	Crizotinib	177-187	ALK receptor tyrosine kinase	Homo sapiens	134-137
23386065-12	2013	The most frequent toxicities with crizotinib include mild visual disturbances, nausea, vomiting, diarrhea, constipation, edema, and generally reversible, sometimes severe, elevations in aspartate aminotransferase and alanine aminotransferase.	Crizotinib	34-44	glutamic--pyruvic transaminase	Homo sapiens	217-241
23386065-13	2013	CONCLUSIONS: Crizotinib is a novel targeted anticancer agent that appears to be a favorable treatment option for patients with locally advanced or metastatic NSCLC that is ALK-positive as detected by an FDA-approved test.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	172-175
23254266-12	2013	Reassessment of the patient revealed new bone metastases and crizotinib was administered since her tumor was found positive for EML4-ALK mutations.	Crizotinib	61-71	EMAP like 4	Homo sapiens	128-132
23254266-12	2013	Reassessment of the patient revealed new bone metastases and crizotinib was administered since her tumor was found positive for EML4-ALK mutations.	Crizotinib	61-71	ALK receptor tyrosine kinase	Homo sapiens	133-136
23328551-0	2013	Successful treatment with crizotinib in mechanically ventilated patients with ALK positive non-small-cell lung cancer.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	78-81
23328551-2	2013	Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor, which is active for advanced non-small cell lung cancer (NSCLC) patients harboring ALK rearrangements.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	17-43
23328551-2	2013	Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor, which is active for advanced non-small cell lung cancer (NSCLC) patients harboring ALK rearrangements.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	45-48
23328551-2	2013	Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor, which is active for advanced non-small cell lung cancer (NSCLC) patients harboring ALK rearrangements.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	144-147
23239810-0	2013	Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated Alk inhibitors.	Crizotinib	0-10	nucleophosmin 1	Homo sapiens	21-24
23239810-0	2013	Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated Alk inhibitors.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	25-28
23239810-0	2013	Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated Alk inhibitors.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	82-85
23239810-1	2013	The dual ALK/MET inhibitor crizotinib was recently approved for the treatment of metastatic and late-stage ALK+ NSCLC, and is currently in clinical trial for other ALK-related diseases.	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	9-12
23239810-1	2013	The dual ALK/MET inhibitor crizotinib was recently approved for the treatment of metastatic and late-stage ALK+ NSCLC, and is currently in clinical trial for other ALK-related diseases.	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	107-110
23239810-1	2013	The dual ALK/MET inhibitor crizotinib was recently approved for the treatment of metastatic and late-stage ALK+ NSCLC, and is currently in clinical trial for other ALK-related diseases.	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	107-110
23239810-3	2013	Here, we focused our attention on the anaplastic large cell lymphoma (ALCL), where the oncogenic fusion protein NPM-ALK, responsible for 70% to 80% of cases, represents an ideal crizotinib target.	Crizotinib	178-188	nucleophosmin 1	Homo sapiens	112-115
23239810-3	2013	Here, we focused our attention on the anaplastic large cell lymphoma (ALCL), where the oncogenic fusion protein NPM-ALK, responsible for 70% to 80% of cases, represents an ideal crizotinib target.	Crizotinib	178-188	ALK receptor tyrosine kinase	Homo sapiens	116-119
23239810-4	2013	We selected and characterized 2 human NPM-ALK+ ALCL cell lines, KARPAS-299 and SUP-M2, able to survive and proliferate at different crizotinib concentrations.	Crizotinib	132-142	nucleophosmin 1	Homo sapiens	38-41
23239810-5	2013	Sequencing of ALK kinase domain revealed that a single mutation became predominant at high crizotinib doses in each cell line, namely L1196Q and I1171N in Karpas-299 and SUP-M2 cells, respectively.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	14-17
23239810-6	2013	These mutations also conferred resistance to crizotinib in Ba/F3 cells expressing human NPM-ALK.	Crizotinib	45-55	nucleophosmin 1	Homo sapiens	88-91
23239810-6	2013	These mutations also conferred resistance to crizotinib in Ba/F3 cells expressing human NPM-ALK.	Crizotinib	45-55	ALK receptor tyrosine kinase	Homo sapiens	92-95
23201355-11	2013	Currently, crizotinib has been approved by the US Food and Drug Administration for the treatment of ALK-positive non-small cell lung cancer along with an approved fluorescence in situ hybridization kit used for the diagnosis of the disease.	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	100-103
23201355-13	2013	About 28% of the cases of crizotinib resistance are related to nearly a dozen different mutations of ALK in the EML4-ALK fusion protein; the other cases of resistance are related to the upregulation of alternative signaling pathways or to undefined mechanisms.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	101-104
23201355-13	2013	About 28% of the cases of crizotinib resistance are related to nearly a dozen different mutations of ALK in the EML4-ALK fusion protein; the other cases of resistance are related to the upregulation of alternative signaling pathways or to undefined mechanisms.	Crizotinib	26-36	EMAP like 4	Homo sapiens	112-116
23201355-13	2013	About 28% of the cases of crizotinib resistance are related to nearly a dozen different mutations of ALK in the EML4-ALK fusion protein; the other cases of resistance are related to the upregulation of alternative signaling pathways or to undefined mechanisms.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	117-120
23201355-14	2013	It is remarkable that the EML4-ALK fusion protein was discovered in 2007 and crizotinib was approved for the treatment of ALK-positive non-small cell lung cancer in 2011, which is a remarkably short timeframe in the overall scheme of drug discovery.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	122-125
22948846-5	2013	Treatment of LU0858 with crizotinib, a small molecule inhibitor for ALK and c-MET, inhibited tumor growth and c-MET activity.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	68-71
22948846-5	2013	Treatment of LU0858 with crizotinib, a small molecule inhibitor for ALK and c-MET, inhibited tumor growth and c-MET activity.	Crizotinib	25-35	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	76-81
22948846-5	2013	Treatment of LU0858 with crizotinib, a small molecule inhibitor for ALK and c-MET, inhibited tumor growth and c-MET activity.	Crizotinib	25-35	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	110-115
22948846-6	2013	Combination of erlotinib and crizotinib caused complete response, indicating the activation of both EGFR and c-MET promote its growth/survival.	Crizotinib	29-39	epidermal growth factor receptor	Homo sapiens	100-104
22948846-6	2013	Combination of erlotinib and crizotinib caused complete response, indicating the activation of both EGFR and c-MET promote its growth/survival.	Crizotinib	29-39	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	109-114
28210129-3	2013	The advent of molecularly targeted therapies that inhibit ALK has allowed the pairing of ALK inhibitors such as crizotinib as treatment for ALK-positive NSCLC, yielding dramatic responses and long-term disease control.	Crizotinib	112-122	ALK receptor tyrosine kinase	Homo sapiens	58-61
28210129-3	2013	The advent of molecularly targeted therapies that inhibit ALK has allowed the pairing of ALK inhibitors such as crizotinib as treatment for ALK-positive NSCLC, yielding dramatic responses and long-term disease control.	Crizotinib	112-122	ALK receptor tyrosine kinase	Homo sapiens	89-92
28210129-3	2013	The advent of molecularly targeted therapies that inhibit ALK has allowed the pairing of ALK inhibitors such as crizotinib as treatment for ALK-positive NSCLC, yielding dramatic responses and long-term disease control.	Crizotinib	112-122	ALK receptor tyrosine kinase	Homo sapiens	89-92
23714542-7	2013	Patients with EGFR mutations or ALK fusions should be treated with erlotinib or crizotinib, respectively, even in patients with tumor-related poor performance.	Crizotinib	80-90	epidermal growth factor receptor	Homo sapiens	14-18
23129213-0	2013	Prediction of crizotinib-midazolam interaction using the Simcyp population-based simulator: comparison of CYP3A time-dependent inhibition between human liver microsomes versus hepatocytes.	Crizotinib	14-24	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	106-111
23714542-7	2013	Patients with EGFR mutations or ALK fusions should be treated with erlotinib or crizotinib, respectively, even in patients with tumor-related poor performance.	Crizotinib	80-90	ALK receptor tyrosine kinase	Homo sapiens	32-35
23671386-5	2013	The discovery of ALK rearrangements in NSCLC serendipitously coincided with the development of crizotinib for other ALK or MET driven malignancies.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	17-20
22887466-1	2013	BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) is highly responsive to crizotinib.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	12-38
22887466-1	2013	BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) is highly responsive to crizotinib.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	40-43
23671386-5	2013	The discovery of ALK rearrangements in NSCLC serendipitously coincided with the development of crizotinib for other ALK or MET driven malignancies.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	116-119
23671386-6	2013	The clinical development of crizotinib for ALK-positive NSCLC patients has been an amazing success story of translational medicine that relied on the prior clinical experience of other targeted predecessors (i.e. erlotinib in EGFR mutant NSCLC) and a compound ready for clinical development to gain expedited FDA approval.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	43-46
23671386-6	2013	The clinical development of crizotinib for ALK-positive NSCLC patients has been an amazing success story of translational medicine that relied on the prior clinical experience of other targeted predecessors (i.e. erlotinib in EGFR mutant NSCLC) and a compound ready for clinical development to gain expedited FDA approval.	Crizotinib	28-38	epidermal growth factor receptor	Homo sapiens	226-230
24326223-7	2013	Treatment of ELM4-ALK mice with crizotinib yielded 65% reduction in tumor size and thus demonstrated the utility of quantitative muCT in longitudinal preclinical trials.	Crizotinib	32-42	anaplastic lymphoma kinase	Mus musculus	18-21
22973962-2	2013	Since c-Met is a marker of pancreatic-cancer-stem-cells (CSC), playing a key role in metastasis and chemoresistance, this study evaluated the therapeutic potential of the novel c-Met/ALK inhibitor crizotinib against PDAC cells, including the Capan-1-gemcitabine-resistant cells (Capan-1-R).	Crizotinib	197-207	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	177-182
24592134-2	2013	The efficacy of crizotinib was shown in lung cancer patients harbouring ALK rearrangement.	Crizotinib	16-26	ALK receptor tyrosine kinase	Homo sapiens	72-75
23394083-10	2013	Crizotinib, an orally ALK and met proto-oncogene (MET) inhibitor, was very well tolerated and produced dramatic antitumor activity in early-stage trials which facilitated a faster than normal move into late-stage trials for EML4-ALK -positive NSCLC patients treatment.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	22-25
23394083-10	2013	Crizotinib, an orally ALK and met proto-oncogene (MET) inhibitor, was very well tolerated and produced dramatic antitumor activity in early-stage trials which facilitated a faster than normal move into late-stage trials for EML4-ALK -positive NSCLC patients treatment.	Crizotinib	0-10	EMAP like 4	Homo sapiens	224-228
23394083-10	2013	Crizotinib, an orally ALK and met proto-oncogene (MET) inhibitor, was very well tolerated and produced dramatic antitumor activity in early-stage trials which facilitated a faster than normal move into late-stage trials for EML4-ALK -positive NSCLC patients treatment.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	229-232
23169500-0	2013	Severe acute interstitial lung disease after crizotinib therapy in a patient with EML4-ALK-positive non-small-cell lung cancer.	Crizotinib	45-55	EMAP like 4	Homo sapiens	82-86
23169500-0	2013	Severe acute interstitial lung disease after crizotinib therapy in a patient with EML4-ALK-positive non-small-cell lung cancer.	Crizotinib	45-55	ALK receptor tyrosine kinase	Homo sapiens	87-90
23246132-1	2013	Anaplastic lymphoma kinase gene (ALK) fusions have been identified in approximately 5% of non-small-cell lung carcinomas (NSCLCs) and define a distinct subpopulation of patients with lung cancer who are highly responsive to ALK kinase inhibitors, such as crizotinib.	Crizotinib	255-265	ALK receptor tyrosine kinase	Homo sapiens	0-31
23246132-1	2013	Anaplastic lymphoma kinase gene (ALK) fusions have been identified in approximately 5% of non-small-cell lung carcinomas (NSCLCs) and define a distinct subpopulation of patients with lung cancer who are highly responsive to ALK kinase inhibitors, such as crizotinib.	Crizotinib	255-265	ALK receptor tyrosine kinase	Homo sapiens	33-36
23918070-7	2013	The inhibitor of the EML4/ALK fusion protein, crizotinib, has recently become a standard second-line treatment for patients with the gene rearrangement and has promise for patients with the ROS1 rearrangement.	Crizotinib	46-56	EMAP like 4	Homo sapiens	21-25
23918070-7	2013	The inhibitor of the EML4/ALK fusion protein, crizotinib, has recently become a standard second-line treatment for patients with the gene rearrangement and has promise for patients with the ROS1 rearrangement.	Crizotinib	46-56	ALK receptor tyrosine kinase	Homo sapiens	26-29
23918070-7	2013	The inhibitor of the EML4/ALK fusion protein, crizotinib, has recently become a standard second-line treatment for patients with the gene rearrangement and has promise for patients with the ROS1 rearrangement.	Crizotinib	46-56	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	190-194
23774148-1	2013	BACKGROUND: Crizotinib, an inhibitor of the anaplastic lymphoma kinase (ALK), is approved since 2012 in Switzerland for use in ALK-rearranged advanced pretreated non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	44-70
23774148-1	2013	BACKGROUND: Crizotinib, an inhibitor of the anaplastic lymphoma kinase (ALK), is approved since 2012 in Switzerland for use in ALK-rearranged advanced pretreated non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	72-75
23774148-1	2013	BACKGROUND: Crizotinib, an inhibitor of the anaplastic lymphoma kinase (ALK), is approved since 2012 in Switzerland for use in ALK-rearranged advanced pretreated non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	127-130
23774148-2	2013	PATIENTS AND METHODS: Here we describe our own experience with crizotinib and ALK testing via fluorescence in-situ hybridization (FISH) in the first 10 ALK-positive patients who were treated in central Switzerland in 2011 on a compassionate use basis.	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	152-155
22973962-2	2013	Since c-Met is a marker of pancreatic-cancer-stem-cells (CSC), playing a key role in metastasis and chemoresistance, this study evaluated the therapeutic potential of the novel c-Met/ALK inhibitor crizotinib against PDAC cells, including the Capan-1-gemcitabine-resistant cells (Capan-1-R).	Crizotinib	197-207	ALK receptor tyrosine kinase	Homo sapiens	183-186
22743652-1	2012	Chromosomal rearrangements leading to constitutive activation of anaplastic lymphoma receptor tyrosine kinase (ALK) define a category of lung adenocarcinomas that may be amenable to targeted therapy with the ALK inhibitor crizotinib.	Crizotinib	222-232	ALK receptor tyrosine kinase	Homo sapiens	111-114
23418494-9	2013	The ALK/MET/ROS1 kinase inhibitor, crizotinib, suppressed fusion-induced anchorage-independent growth of NIH3T3 cells.	Crizotinib	35-45	Ros1 proto-oncogene	Mus musculus	12-16
28210128-7	2012	Crizotinib is the first orally active inhibitor of receptor tyrosine kinases, including ALK and ROS1, in clinical practice.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	88-91
28210128-7	2012	Crizotinib is the first orally active inhibitor of receptor tyrosine kinases, including ALK and ROS1, in clinical practice.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	96-100
22286764-6	2012	Further, this stimulation of MYCN gene transcription and de novo MYCN protein expression is abrogated by specific ALK inhibitors, such as crizotinib (PF-2341066), NVP-TAE684, and by small interfering RNA to ALK resulting in a decrease in proliferation rate.	Crizotinib	138-148	MYCN proto-oncogene, bHLH transcription factor	Homo sapiens	29-33
22286764-6	2012	Further, this stimulation of MYCN gene transcription and de novo MYCN protein expression is abrogated by specific ALK inhibitors, such as crizotinib (PF-2341066), NVP-TAE684, and by small interfering RNA to ALK resulting in a decrease in proliferation rate.	Crizotinib	138-148	MYCN proto-oncogene, bHLH transcription factor	Homo sapiens	65-69
22286764-6	2012	Further, this stimulation of MYCN gene transcription and de novo MYCN protein expression is abrogated by specific ALK inhibitors, such as crizotinib (PF-2341066), NVP-TAE684, and by small interfering RNA to ALK resulting in a decrease in proliferation rate.	Crizotinib	138-148	ALK receptor tyrosine kinase	Homo sapiens	114-117
22286764-6	2012	Further, this stimulation of MYCN gene transcription and de novo MYCN protein expression is abrogated by specific ALK inhibitors, such as crizotinib (PF-2341066), NVP-TAE684, and by small interfering RNA to ALK resulting in a decrease in proliferation rate.	Crizotinib	138-148	ALK receptor tyrosine kinase	Homo sapiens	207-210
23232172-3	2012	In comparison to other targeted agents such v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitors in melanoma or crizotinib in anaplastic lymphoma receptor tyrosine kinase (ALK) translocated tumors, the number of objective responses to PI3K inhibitors is less dramatic.	Crizotinib	124-134	anaplastic lymphoma kinase	Mus musculus	184-187
22986231-3	2012	Targeting EML4-ALK with Crizotinib in this subset of NSCLC has documented therapeutic efficacy, but the vast majority of patients eventually develop recurrent disease that is often refractory to further treatments.	Crizotinib	24-34	EMAP like 4	Homo sapiens	10-14
22986231-3	2012	Targeting EML4-ALK with Crizotinib in this subset of NSCLC has documented therapeutic efficacy, but the vast majority of patients eventually develop recurrent disease that is often refractory to further treatments.	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	15-18
22986231-6	2012	Results of ongoing clinical trials will clarify whether the CNS is a major sanctuary site for EML4-ALK positive NSCLC being treated with Crizotinib.	Crizotinib	137-147	EMAP like 4	Homo sapiens	94-98
22986231-6	2012	Results of ongoing clinical trials will clarify whether the CNS is a major sanctuary site for EML4-ALK positive NSCLC being treated with Crizotinib.	Crizotinib	137-147	ALK receptor tyrosine kinase	Homo sapiens	99-102
22920921-3	2012	Crizotinib, an oral ALK inhibitor, has proved to provide dramatic clinical benefit in patients with NSCLC harboring ALK rearrangements.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	20-23
22920921-3	2012	Crizotinib, an oral ALK inhibitor, has proved to provide dramatic clinical benefit in patients with NSCLC harboring ALK rearrangements.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	116-119
22920921-6	2012	Thus, the identification of the molecular mechanisms of crizotinib resistance will be strictly required in order to pursue the appropriate therapeutic options for patients with ALK-rearranged tumors.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	177-180
23154552-7	2012	RESULTS: Median progression-free survival in ALK+ patients on crizotinib was 9.0 months, and 13.8 months for EGFR-MT patients on erlotinib.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	45-48
23324244-0	2012	[Mechanisms of resistance to crizotinib in patients with transforming EML4-ALK fusion gene].	Crizotinib	29-39	EMAP like 4	Homo sapiens	70-74
23324244-0	2012	[Mechanisms of resistance to crizotinib in patients with transforming EML4-ALK fusion gene].	Crizotinib	29-39	ALK receptor tyrosine kinase	Homo sapiens	75-78
22843788-1	2012	PURPOSE: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) such as crizotinib show marked efficacy in patients with non-small cell lung cancer positive for the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion protein.	Crizotinib	83-93	ALK receptor tyrosine kinase	Homo sapiens	9-35
22843788-1	2012	PURPOSE: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) such as crizotinib show marked efficacy in patients with non-small cell lung cancer positive for the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion protein.	Crizotinib	83-93	ALK receptor tyrosine kinase	Homo sapiens	37-40
22843788-1	2012	PURPOSE: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) such as crizotinib show marked efficacy in patients with non-small cell lung cancer positive for the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion protein.	Crizotinib	83-93	EMAP like 4	Homo sapiens	176-224
22843788-1	2012	PURPOSE: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) such as crizotinib show marked efficacy in patients with non-small cell lung cancer positive for the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion protein.	Crizotinib	83-93	EMAP like 4	Homo sapiens	226-230
22843788-1	2012	PURPOSE: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) such as crizotinib show marked efficacy in patients with non-small cell lung cancer positive for the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion protein.	Crizotinib	83-93	ALK receptor tyrosine kinase	Homo sapiens	232-235
22843788-4	2012	We isolated EML4-ALK-positive lung cancer cells (K-3) from a patient who developed resistance to crizotinib and investigated their characteristics.	Crizotinib	97-107	EMAP like 4	Homo sapiens	12-16
22843788-4	2012	We isolated EML4-ALK-positive lung cancer cells (K-3) from a patient who developed resistance to crizotinib and investigated their characteristics.	Crizotinib	97-107	ALK receptor tyrosine kinase	Homo sapiens	17-20
22488744-6	2012	Only 1 in 5 patients who had anaplastic lymphoma kinase (ALK) gene rearrangements and had not yet received crizotinib had low T. The initiation of crizotinib in 2 patients who had previously normal T levels was associated with a rapid decreases in T and in luteinizing hormone and follicle stimulating hormone levels within 14 to 21 days.	Crizotinib	147-157	ALK receptor tyrosine kinase	Homo sapiens	29-55
22266870-8	2012	Treatment of neuroblastoma cells with the dual Met/ALK inhibitor crizotinib sensitized cells to antibody-induced growth inhibition by promoting cell surface accumulation of ALK and thus increasing the accessibility of antigen for antibody binding.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	51-54
22266870-8	2012	Treatment of neuroblastoma cells with the dual Met/ALK inhibitor crizotinib sensitized cells to antibody-induced growth inhibition by promoting cell surface accumulation of ALK and thus increasing the accessibility of antigen for antibody binding.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	173-176
22743652-1	2012	Chromosomal rearrangements leading to constitutive activation of anaplastic lymphoma receptor tyrosine kinase (ALK) define a category of lung adenocarcinomas that may be amenable to targeted therapy with the ALK inhibitor crizotinib.	Crizotinib	222-232	ALK receptor tyrosine kinase	Homo sapiens	208-211
22743654-2	2012	Recently, the ALK protein inhibitor crizotinib was shown to be an effective therapy in patients with ALK-rearranged non-small cell lung cancer.	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	14-17
22743654-2	2012	Recently, the ALK protein inhibitor crizotinib was shown to be an effective therapy in patients with ALK-rearranged non-small cell lung cancer.	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	101-104
22932897-2	2012	Small molecule inhibitors targeting the kinase activity of ALK have proven to be effective therapies in certain ALK-driven malignancies and one such inhibitor, crizotinib, is now approved for the treatment of EML4-ALK-driven, non-small cell lung cancer.	Crizotinib	160-170	ALK receptor tyrosine kinase	Homo sapiens	59-62
22954506-0	2012	Crizotinib in ALK-positive lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	14-17
22932897-2	2012	Small molecule inhibitors targeting the kinase activity of ALK have proven to be effective therapies in certain ALK-driven malignancies and one such inhibitor, crizotinib, is now approved for the treatment of EML4-ALK-driven, non-small cell lung cancer.	Crizotinib	160-170	EMAP like 4	Homo sapiens	209-213
23020724-1	2012	Crizotinib (Xalkori), the first inhibitor of both anaplastic lymphoma kinase (ALK) and c-Met receptor kinases, has been approved in the United States, Korea, and other countries for the treatment of ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	50-76
23020724-1	2012	Crizotinib (Xalkori), the first inhibitor of both anaplastic lymphoma kinase (ALK) and c-Met receptor kinases, has been approved in the United States, Korea, and other countries for the treatment of ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	78-81
23020724-1	2012	Crizotinib (Xalkori), the first inhibitor of both anaplastic lymphoma kinase (ALK) and c-Met receptor kinases, has been approved in the United States, Korea, and other countries for the treatment of ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	199-202
23020724-3	2012	Oral crizotinib 250 mg twice daily showed excellent efficacy in patients with advanced ALK-positive NSCLC, with objective response rates of 61% and 51% in ongoing phase I and II studies, respectively.	Crizotinib	5-15	ALK receptor tyrosine kinase	Homo sapiens	87-90
23020724-8	2012	Phase III studies investigating crizotinib for the first- and second-line treatment of advanced ALK-positive NSCLC, versus current standards of care, are ongoing.	Crizotinib	32-42	ALK receptor tyrosine kinase	Homo sapiens	96-99
23020724-9	2012	Crizotinib represents a new standard of care for patients with ALK-positive NSCLC and highlights the importance of the role of the pathologist, as molecular profiling becomes a part of initial workups for newly diagnosed patients with NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	63-66
22954507-0	2012	Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study.	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	51-54
22954507-2	2012	We assessed the tolerability and activity of crizotinib in patients with NSCLC who were prospectively identified to have an ALK fusion within the first-in-man phase 1 crizotinib study.	Crizotinib	45-55	ALK receptor tyrosine kinase	Homo sapiens	124-127
22954507-3	2012	METHODS: In this phase 1 study, patients with ALK-positive stage III or IV NSCLC received oral crizotinib 250 mg twice daily in 28-day cycles.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	46-49
22954507-17	2012	INTERPRETATION: Crizotinib is well tolerated with rapid, durable responses in patients with ALK-positive NSCLC.	Crizotinib	16-26	ALK receptor tyrosine kinase	Homo sapiens	92-95
22940474-0	2012	Liquid chromatography-tandem mass spectrometric assay for the ALK inhibitor crizotinib in mouse plasma.	Crizotinib	76-86	anaplastic lymphoma kinase	Mus musculus	62-65
22891268-0	2012	Response to crizotinib in ROS1-rearranged non-small-cell lung cancer.	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	26-30
22940474-1	2012	A quantitative bioanalytical liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay for the ALK inhibitor crizotinib was developed and validated.	Crizotinib	116-126	anaplastic lymphoma kinase	Mus musculus	102-105
22987955-5	2012	Then, in the face of a strong rationale, mammalian target of rapamycin (mTOR) inhibitors are active in a proportion of PEComas (perivascular epithelioid cell tumours) and crizotinib in ALK-rearranged inflammatory myofibroblastic tumours.	Crizotinib	171-181	mechanistic target of rapamycin kinase	Homo sapiens	72-76
22987955-5	2012	Then, in the face of a strong rationale, mammalian target of rapamycin (mTOR) inhibitors are active in a proportion of PEComas (perivascular epithelioid cell tumours) and crizotinib in ALK-rearranged inflammatory myofibroblastic tumours.	Crizotinib	171-181	ALK receptor tyrosine kinase	Homo sapiens	185-188
23006951-8	2012	Crizotinib is an inhibitor of ALK tyrosine kinase that has been approved for the treatment of ALK non-small cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	30-33
23006951-8	2012	Crizotinib is an inhibitor of ALK tyrosine kinase that has been approved for the treatment of ALK non-small cell lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	94-97
23006951-9	2012	Successful treatment of ALK ALCL with crizotinib has been reported in pediatric patients and small case series leading to ongoing trials in relapsed/refractory ALCL.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	24-27
23006951-10	2012	Brentuximab vedotin and crizotinib represent major advances in the treatment of ALK and ALK ALCL and will likely result in marked improvement in prognosis for this subset of aggressive lymphomas.	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	80-83
23006951-10	2012	Brentuximab vedotin and crizotinib represent major advances in the treatment of ALK and ALK ALCL and will likely result in marked improvement in prognosis for this subset of aggressive lymphomas.	Crizotinib	24-34	ALK receptor tyrosine kinase	Homo sapiens	88-91
22912387-6	2012	RESULTS: Different ALK fusion genes and EML4-ALK variants exhibited differential sensitivity to the structurally diverse ALK kinase inhibitors crizotinib and TAE684.	Crizotinib	143-153	anaplastic lymphoma kinase	Mus musculus	19-22
22912387-6	2012	RESULTS: Different ALK fusion genes and EML4-ALK variants exhibited differential sensitivity to the structurally diverse ALK kinase inhibitors crizotinib and TAE684.	Crizotinib	143-153	echinoderm microtubule associated protein like 4	Mus musculus	40-44
22912387-6	2012	RESULTS: Different ALK fusion genes and EML4-ALK variants exhibited differential sensitivity to the structurally diverse ALK kinase inhibitors crizotinib and TAE684.	Crizotinib	143-153	anaplastic lymphoma kinase	Mus musculus	45-48
22912387-6	2012	RESULTS: Different ALK fusion genes and EML4-ALK variants exhibited differential sensitivity to the structurally diverse ALK kinase inhibitors crizotinib and TAE684.	Crizotinib	143-153	anaplastic lymphoma kinase	Mus musculus	45-48
22912388-0	2012	Variants on a theme: a biomarker of crizotinib response in ALK-positive non-small cell lung cancer?	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	59-62
22912388-1	2012	Anaplastic lymphoma kinase (ALK) gene rearrangements are found in approximately 5% of non-small cell lung carcinoma patients and confer sensitivity to ALK inhibitors such as crizotinib.	Crizotinib	174-184	ALK receptor tyrosine kinase	Homo sapiens	0-26
22912388-1	2012	Anaplastic lymphoma kinase (ALK) gene rearrangements are found in approximately 5% of non-small cell lung carcinoma patients and confer sensitivity to ALK inhibitors such as crizotinib.	Crizotinib	174-184	ALK receptor tyrosine kinase	Homo sapiens	28-31
22912388-1	2012	Anaplastic lymphoma kinase (ALK) gene rearrangements are found in approximately 5% of non-small cell lung carcinoma patients and confer sensitivity to ALK inhibitors such as crizotinib.	Crizotinib	174-184	ALK receptor tyrosine kinase	Homo sapiens	151-154
22912388-2	2012	The particular ALK fusion expressed may have an impact on protein stability and sensitivity to crizotinib, and this may underlie the heterogeneity in responses observed in the clinic.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	15-18
22919003-6	2012	In addition, the clinical efficacy of ROS1 inhibition was assessed by treating a ROS1-positive patient with crizotinib.	Crizotinib	108-118	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	38-42
22919003-6	2012	In addition, the clinical efficacy of ROS1 inhibition was assessed by treating a ROS1-positive patient with crizotinib.	Crizotinib	108-118	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	81-85
22968692-3	2012	On August 2011, a small molecule inhibitor against ALK, crizotinib, was approved for therapy against NSCLC with ALK translocations.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	51-54
22282074-0	2012	Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization-positive nonsmall cell lung cancer.	Crizotinib	155-165	ALK receptor tyrosine kinase	Homo sapiens	90-93
29776229-1	2012	BACKGROUND: Fusions and translocations of the ALK gene are an important genetic marker in different types of cancer and are therapy relevant, especially in lung cancer, as they predict the patient"s response to crizotinib therapy.	Crizotinib	211-221	ALK receptor tyrosine kinase	Homo sapiens	46-49
22895149-0	2012	Next-generation sequencing identifies and immunohistochemistry confirms a novel crizotinib-sensitive ALK rearrangement in a patient with metastatic non-small-cell lung cancer.	Crizotinib	80-90	ALK receptor tyrosine kinase	Homo sapiens	101-104
22968692-3	2012	On August 2011, a small molecule inhibitor against ALK, crizotinib, was approved for therapy against NSCLC with ALK translocations.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	112-115
22789543-1	2012	The ALK(F1174L) mutation is associated with intrinsic and acquired resistance to crizotinib and cosegregates with MYCN in neuroblastoma.	Crizotinib	81-91	anaplastic lymphoma kinase	Mus musculus	4-10
22568572-3	2012	A small-molecule tyrosine kinase inhibitor of ALK, crizotinib, shows pronounced clinical activity in the treatment of patients with NSCLC positive for EML4-ALK, and it has rapidly entered into daily clinical practice.	Crizotinib	51-61	ALK receptor tyrosine kinase	Homo sapiens	46-49
22568572-3	2012	A small-molecule tyrosine kinase inhibitor of ALK, crizotinib, shows pronounced clinical activity in the treatment of patients with NSCLC positive for EML4-ALK, and it has rapidly entered into daily clinical practice.	Crizotinib	51-61	EMAP like 4	Homo sapiens	151-155
22568572-3	2012	A small-molecule tyrosine kinase inhibitor of ALK, crizotinib, shows pronounced clinical activity in the treatment of patients with NSCLC positive for EML4-ALK, and it has rapidly entered into daily clinical practice.	Crizotinib	51-61	ALK receptor tyrosine kinase	Homo sapiens	156-159
22789543-5	2012	Combined treatment with the ATP-competitive mTOR inhibitor Torin2 overcame the resistance of ALK(F1174L)/MYCN tumors to crizotinib.	Crizotinib	120-130	mechanistic target of rapamycin kinase	Mus musculus	44-48
22233293-1	2012	BACKGROUND AND PURPOSE: Besides targeting the well-known oncogenic c-Met, crizotinib is the first oral tyrosine kinase inhibitor inhibiting anaplastic lymphoma kinase (ALK) in clinical trials for the treatment of non-small cell lung cancer.	Crizotinib	74-84	met proto-oncogene	Mus musculus	67-72
22547770-5	2012	This review focuses on the ALK-inhibitory activity of crizotinib in preclinical and clinical trials that led to approval, as well as the diagnostic methods to classify patients with ALK-positive NSCLC.	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	27-30
22547770-0	2012	Crizotinib for ALK-rearranged non-small cell lung cancer: a new targeted therapy for a new target.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	15-18
22547770-1	2012	Crizotinib (PF02341066, Xalkori; Pfizer) was recently approved by the U.S. Food and Drug Administration for treatment of ALK-positive non-small cell lung cancer (NSCLC) as defined by a jointly approved diagnostic test using a break-apart fluorescence in situ hybridization assay.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	121-124
22233293-4	2012	To understand the mechanisms for MDR reversal, the alterations of intracellular doxorubicin or rhodamine 123 accumulation, doxorubicin efflux, ABCB1 expression level, ATPase activity of ABCB1 and crizotinib-induced c-Met, Akt and ERK1/2 phosphorylation were examined.	Crizotinib	196-206	met proto-oncogene	Mus musculus	215-220
22233293-5	2012	KEY RESULTS: Crizotinib significantly enhanced the cytotoxicity of chemotherapeutic agents which are also ABCB1 substrates, in MDR cells with no effect found on sensitive cells in vitro and in vivo.	Crizotinib	13-23	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	106-111
22233293-6	2012	Additionally, crizotinib significantly increased intracellular accumulation of rhodamine 123 and doxorubicin and inhibited the drug efflux in ABCB1-overexpressing MDR cells.	Crizotinib	14-24	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	142-147
22233293-7	2012	Further studies showed that crizotinib enhanced the ATPase activity of ABCB1 in a concentration-dependent manner.	Crizotinib	28-38	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	71-76
22233293-10	2012	CONCLUSIONS AND IMPLICATIONS: Crizotinib reversed ABCB1-mediated MDR by inhibiting ABCB1 transport function without affecting ABCB1 expression or blocking the Akt or ERK1/2 pathways.	Crizotinib	30-40	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	50-55
22233293-10	2012	CONCLUSIONS AND IMPLICATIONS: Crizotinib reversed ABCB1-mediated MDR by inhibiting ABCB1 transport function without affecting ABCB1 expression or blocking the Akt or ERK1/2 pathways.	Crizotinib	30-40	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	83-88
22233293-10	2012	CONCLUSIONS AND IMPLICATIONS: Crizotinib reversed ABCB1-mediated MDR by inhibiting ABCB1 transport function without affecting ABCB1 expression or blocking the Akt or ERK1/2 pathways.	Crizotinib	30-40	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	83-88
22713522-1	2012	Crizotinib, an inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK), achieves response rates of 57 % at eight weeks in patients with stage IV non-small cell lung cancer with ALK rearrangements.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	85-88
22713522-1	2012	Crizotinib, an inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK), achieves response rates of 57 % at eight weeks in patients with stage IV non-small cell lung cancer with ALK rearrangements.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	196-199
22617245-0	2012	Preclinical rationale for use of the clinically available multitargeted tyrosine kinase inhibitor crizotinib in ROS1-translocated lung cancer.	Crizotinib	98-108	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	112-116
22664824-4	2012	RECENT FINDINGS: A recent phase I dose-escalation trial of the selective MET/ALK inhibitor crizotinib showed a long-term partial response in a patient with IMT carrying an ALK translocation but not in a patient with ALK-negative disease.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	77-80
22664824-4	2012	RECENT FINDINGS: A recent phase I dose-escalation trial of the selective MET/ALK inhibitor crizotinib showed a long-term partial response in a patient with IMT carrying an ALK translocation but not in a patient with ALK-negative disease.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	172-175
22664824-4	2012	RECENT FINDINGS: A recent phase I dose-escalation trial of the selective MET/ALK inhibitor crizotinib showed a long-term partial response in a patient with IMT carrying an ALK translocation but not in a patient with ALK-negative disease.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	172-175
22664824-9	2012	Development of more selective ALK inhibitors, which can overcome emergent crizotinib resistance mutations, as well as development of combination treatments with drugs targeting compensatory pathways, will be key to achieving therapeutic success in targeting this potent and prevalent oncogenic driver.	Crizotinib	74-84	ALK receptor tyrosine kinase	Homo sapiens	30-33
22269210-5	2012	Interestingly, Crizotinib (a dual inhibitor of c-Met and ALK pathways) as single agent or in combination with sunitinib reduced metastasis in all models tested suggesting a role for c-Met/HGF pathway in intrinsic- or sunitinib-induced-metastasis.	Crizotinib	15-25	met proto-oncogene	Mus musculus	47-52
22269210-5	2012	Interestingly, Crizotinib (a dual inhibitor of c-Met and ALK pathways) as single agent or in combination with sunitinib reduced metastasis in all models tested suggesting a role for c-Met/HGF pathway in intrinsic- or sunitinib-induced-metastasis.	Crizotinib	15-25	anaplastic lymphoma kinase	Mus musculus	57-60
22269210-5	2012	Interestingly, Crizotinib (a dual inhibitor of c-Met and ALK pathways) as single agent or in combination with sunitinib reduced metastasis in all models tested suggesting a role for c-Met/HGF pathway in intrinsic- or sunitinib-induced-metastasis.	Crizotinib	15-25	met proto-oncogene	Mus musculus	182-187
22269210-5	2012	Interestingly, Crizotinib (a dual inhibitor of c-Met and ALK pathways) as single agent or in combination with sunitinib reduced metastasis in all models tested suggesting a role for c-Met/HGF pathway in intrinsic- or sunitinib-induced-metastasis.	Crizotinib	15-25	hepatocyte growth factor	Mus musculus	188-191
22617245-6	2012	Crizotinib displayed dose-dependent inhibition of anaplastic lymphoma kinase translocated NCI-H3122 and also ROS1--translocated HCC78.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	109-113
22617245-7	2012	The SLC34A2-ROS1 translocated HCC78 cell line had phosphorylated levels of ROS1, AKT, and ERK inhibited by submicromolar doses of crizotinib, and subsequently underwent apoptosis.	Crizotinib	130-140	solute carrier family 34 member 2	Homo sapiens	4-11
22617245-7	2012	The SLC34A2-ROS1 translocated HCC78 cell line had phosphorylated levels of ROS1, AKT, and ERK inhibited by submicromolar doses of crizotinib, and subsequently underwent apoptosis.	Crizotinib	130-140	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	12-16
22617245-7	2012	The SLC34A2-ROS1 translocated HCC78 cell line had phosphorylated levels of ROS1, AKT, and ERK inhibited by submicromolar doses of crizotinib, and subsequently underwent apoptosis.	Crizotinib	130-140	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	75-79
22617245-7	2012	The SLC34A2-ROS1 translocated HCC78 cell line had phosphorylated levels of ROS1, AKT, and ERK inhibited by submicromolar doses of crizotinib, and subsequently underwent apoptosis.	Crizotinib	130-140	AKT serine/threonine kinase 1	Homo sapiens	81-84
22617245-7	2012	The SLC34A2-ROS1 translocated HCC78 cell line had phosphorylated levels of ROS1, AKT, and ERK inhibited by submicromolar doses of crizotinib, and subsequently underwent apoptosis.	Crizotinib	130-140	EPH receptor B2	Homo sapiens	90-93
22617245-8	2012	CONCLUSIONS: The ROS1-translocated HCC78 cell line was sensitive to inhibition by the multitargeted ALK/MET/RON/ROS1 inhibitor crizotinib.	Crizotinib	127-137	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	17-21
22617245-8	2012	CONCLUSIONS: The ROS1-translocated HCC78 cell line was sensitive to inhibition by the multitargeted ALK/MET/RON/ROS1 inhibitor crizotinib.	Crizotinib	127-137	ALK receptor tyrosine kinase	Homo sapiens	100-103
22617245-8	2012	CONCLUSIONS: The ROS1-translocated HCC78 cell line was sensitive to inhibition by the multitargeted ALK/MET/RON/ROS1 inhibitor crizotinib.	Crizotinib	127-137	macrophage stimulating 1 receptor	Homo sapiens	108-111
22617245-8	2012	CONCLUSIONS: The ROS1-translocated HCC78 cell line was sensitive to inhibition by the multitargeted ALK/MET/RON/ROS1 inhibitor crizotinib.	Crizotinib	127-137	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	112-116
22617245-9	2012	Preclinical data supports the clinical development of crizotinib for ROS1-translocated NSCLC.	Crizotinib	54-64	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	69-73
22683780-6	2012	However, leukemic cells treated with the specific MET kinase inhibitor crizotinib developed resistance resulting from compensatory upregulation of HGF expression, leading to the restoration of MET signaling.	Crizotinib	71-81	hepatocyte growth factor	Homo sapiens	147-150
22729845-3	2012	Inhibition of MET signaling by crizotinib or RNA interference-mediated MET depletion resulted in induction of apoptosis accompanied by inhibition of AKT and extracellular signal-regulated kinase phosphorylation in gastric cancer cells with MET amplification but not in those without it, suggesting that MET signaling is essential for the survival of MET amplification-positive cells.	Crizotinib	31-41	AKT serine/threonine kinase 1	Homo sapiens	149-152
22659414-0	2012	A molecular dynamics investigation on the crizotinib resistance mechanism of C1156Y mutation in ALK.	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	96-99
22729845-4	2012	Crizotinib upregulated the expression of BIM, a proapoptotic member of the Bcl-2 family, as well as downregulated that of survivin, X-linked inhibitor of apoptosis protein (XIAP), and c-IAP1, members of the inhibitor of apoptosis protein family, in cells with MET amplification.	Crizotinib	0-10	X-linked inhibitor of apoptosis	Homo sapiens	132-171
22729845-4	2012	Crizotinib upregulated the expression of BIM, a proapoptotic member of the Bcl-2 family, as well as downregulated that of survivin, X-linked inhibitor of apoptosis protein (XIAP), and c-IAP1, members of the inhibitor of apoptosis protein family, in cells with MET amplification.	Crizotinib	0-10	X-linked inhibitor of apoptosis	Homo sapiens	173-177
22729845-4	2012	Crizotinib upregulated the expression of BIM, a proapoptotic member of the Bcl-2 family, as well as downregulated that of survivin, X-linked inhibitor of apoptosis protein (XIAP), and c-IAP1, members of the inhibitor of apoptosis protein family, in cells with MET amplification.	Crizotinib	0-10	baculoviral IAP repeat containing 2	Homo sapiens	184-190
22659414-1	2012	Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor that has recently been approved in the US for the treatment of non-small cell lung carcinoma (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	17-43
22659414-1	2012	Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor that has recently been approved in the US for the treatment of non-small cell lung carcinoma (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	45-48
22659414-5	2012	The results suggest that despite the non-active site mutation, C1156Y causes the dislocation of crizotinib as well as the indirect conformational changes in the binding cavity, which results in a marked decrease in the van der Waals and electrostatic interactions between crizotinib and ALK.	Crizotinib	96-106	ALK receptor tyrosine kinase	Homo sapiens	287-290
22659414-5	2012	The results suggest that despite the non-active site mutation, C1156Y causes the dislocation of crizotinib as well as the indirect conformational changes in the binding cavity, which results in a marked decrease in the van der Waals and electrostatic interactions between crizotinib and ALK.	Crizotinib	272-282	ALK receptor tyrosine kinase	Homo sapiens	287-290
22787409-1	2012	New drugs such as pemetrexed, the epidermal growth factor receptor (egfr) tyrosine kinase inhibitors, and the Alk inhibitor crizotinib have recently enabled progress in the management of advanced non-small-cell lung cancer (nsclc).	Crizotinib	124-134	ALK receptor tyrosine kinase	Homo sapiens	110-113
22787411-11	2012	Maintenance therapy is emerging as a new option for patients, as are targeted therapies for particular molecular subtypes of nsclc, such as crizotinib in tumours harbouring the EML4-ALK gene rearrangement.	Crizotinib	140-150	EMAP like 4	Homo sapiens	177-181
22787411-11	2012	Maintenance therapy is emerging as a new option for patients, as are targeted therapies for particular molecular subtypes of nsclc, such as crizotinib in tumours harbouring the EML4-ALK gene rearrangement.	Crizotinib	140-150	ALK receptor tyrosine kinase	Homo sapiens	182-185
22594847-3	2012	Crizotinib is an oral tyrosine kinase inhibitor (TKI), which silences the protein product of the ALK fusion gene and has recently been approved for the treatment of NSCLC aberrantly expressing ALK.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	97-100
22588779-10	2012	Crizotinib is a dual-specific inhibitor of ALK/Met and inhibits proliferation of neuroblastoma cells harboring R1275Q-mutated ALK or amplified wild-type ALK, but not cells harboring F1174L.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	43-46
22588779-10	2012	Crizotinib is a dual-specific inhibitor of ALK/Met and inhibits proliferation of neuroblastoma cells harboring R1275Q-mutated ALK or amplified wild-type ALK, but not cells harboring F1174L.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	126-129
22588779-10	2012	Crizotinib is a dual-specific inhibitor of ALK/Met and inhibits proliferation of neuroblastoma cells harboring R1275Q-mutated ALK or amplified wild-type ALK, but not cells harboring F1174L.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	126-129
21844131-3	2012	Crizotinib is an oral ATP-competitive selective inhibitor of the ALK and MET tyrosine kinases that inhibits tyrosine phosphorylation of activated ALK at nanomolar concentrations.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	65-68
21844131-3	2012	Crizotinib is an oral ATP-competitive selective inhibitor of the ALK and MET tyrosine kinases that inhibits tyrosine phosphorylation of activated ALK at nanomolar concentrations.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	146-149
21844131-6	2012	CONCLUSION: The ALK receptor tyrosine kinase inhibitor crizotinib may be an effective therapy in ALK mutated NSCLC and is currently being compared to standard chemotherapy for advanced or metastatic NSCLC.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	16-19
21844131-6	2012	CONCLUSION: The ALK receptor tyrosine kinase inhibitor crizotinib may be an effective therapy in ALK mutated NSCLC and is currently being compared to standard chemotherapy for advanced or metastatic NSCLC.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	97-100
22506598-2	2012	The ALK inhibitor crizotinib was approved in August 2011 by the US Food and Drug Administration (FDA) for treating late-stage NSCLCs that are ALK+, with a companion fluorescent in situ hybridization (FISH) test using the Vysis ALK Break Apart FISH Probe Kit.	Crizotinib	18-28	ALK receptor tyrosine kinase	Homo sapiens	4-7
22506598-2	2012	The ALK inhibitor crizotinib was approved in August 2011 by the US Food and Drug Administration (FDA) for treating late-stage NSCLCs that are ALK+, with a companion fluorescent in situ hybridization (FISH) test using the Vysis ALK Break Apart FISH Probe Kit.	Crizotinib	18-28	ALK receptor tyrosine kinase	Homo sapiens	142-145
22506598-2	2012	The ALK inhibitor crizotinib was approved in August 2011 by the US Food and Drug Administration (FDA) for treating late-stage NSCLCs that are ALK+, with a companion fluorescent in situ hybridization (FISH) test using the Vysis ALK Break Apart FISH Probe Kit.	Crizotinib	18-28	ALK receptor tyrosine kinase	Homo sapiens	142-145
22564207-1	2012	Anaplastic lymphoma kinase (ALK) is a promising therapeutic target for the treatment of cancer, supported by considerable favorable preclinical and clinical activities over the past several years and culminating in the recent FDA approval of the ALK inhibitor crizotinib.	Crizotinib	260-270	ALK receptor tyrosine kinase	Rattus norvegicus	0-26
22564207-1	2012	Anaplastic lymphoma kinase (ALK) is a promising therapeutic target for the treatment of cancer, supported by considerable favorable preclinical and clinical activities over the past several years and culminating in the recent FDA approval of the ALK inhibitor crizotinib.	Crizotinib	260-270	ALK receptor tyrosine kinase	Rattus norvegicus	28-31
22564207-1	2012	Anaplastic lymphoma kinase (ALK) is a promising therapeutic target for the treatment of cancer, supported by considerable favorable preclinical and clinical activities over the past several years and culminating in the recent FDA approval of the ALK inhibitor crizotinib.	Crizotinib	260-270	ALK receptor tyrosine kinase	Rattus norvegicus	246-249
22585002-5	2012	Crizotinib, a small-molecule inhibitor of ALK, has transformed the                 landscape for the treatment of NSCLC harbouring ALK translocations and has                 demonstrated activity in preclinical models of ALK-driven neuroblastomas.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	42-45
22585002-5	2012	Crizotinib, a small-molecule inhibitor of ALK, has transformed the                 landscape for the treatment of NSCLC harbouring ALK translocations and has                 demonstrated activity in preclinical models of ALK-driven neuroblastomas.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	131-134
22585002-5	2012	Crizotinib, a small-molecule inhibitor of ALK, has transformed the                 landscape for the treatment of NSCLC harbouring ALK translocations and has                 demonstrated activity in preclinical models of ALK-driven neuroblastomas.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	131-134
22693986-0	2012	Treating ALK-positive lung cancer in the weeks after the FDA approval of crizotinib.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	9-12
22594847-3	2012	Crizotinib is an oral tyrosine kinase inhibitor (TKI), which silences the protein product of the ALK fusion gene and has recently been approved for the treatment of NSCLC aberrantly expressing ALK.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	193-196
22614325-5	2012	One of such compound, crizotinib, is now approved in the United States for the treatment of lung cancer positive for ALK rearrangement.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	117-120
22594847-4	2012	Emerging data suggest that crizotinib may also have activity in other subsets of lung cancer, including tumors demonstrating amplification or mutation of the MET oncogene, or translocation of the ROS1 oncogene.	Crizotinib	27-37	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	196-200
22594847-9	2012	Crizotinib has demonstrated efficacy against ALK-rearranged NSCLC, and has potential for broader application in select subsets of lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	45-48
22525302-9	2012	Crizotinib, an ALK inhibitor is a new therapeutic standard in ALK rearranged tumors.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	15-18
22397764-2	2012	The identification of EML4-anaplastic lymphoma kinase (ALK) as an oncogenic driver in non-small cell lung cancer (NSCLC) early in the clinical development of crizotinib and the observation of promising clinical responses in patients with NSCLC harbouring ALK translocations accelerated its clinical development in ALK-positive NSCLC.	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	22-53
22397764-2	2012	The identification of EML4-anaplastic lymphoma kinase (ALK) as an oncogenic driver in non-small cell lung cancer (NSCLC) early in the clinical development of crizotinib and the observation of promising clinical responses in patients with NSCLC harbouring ALK translocations accelerated its clinical development in ALK-positive NSCLC.	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	55-58
22397764-3	2012	Phase I and II trials of crizotinib in patients with ALK-positive advanced NSCLC reported notably high response rates that tended to be rapid and of prolonged duration.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	53-56
22525302-9	2012	Crizotinib, an ALK inhibitor is a new therapeutic standard in ALK rearranged tumors.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	62-65
22385925-0	2012	ALK inhibitor crizotinib combined with intrathecal methotrexate treatment for non-small cell lung cancer with leptomeningeal carcinomatosis.	Crizotinib	14-24	ALK receptor tyrosine kinase	Homo sapiens	0-3
22536569-1	2012	Crizotinib is a potent small-molecule inhibitor of ALK tyrosine kinase receptor (anaplastic lymphoma kinase; ALK) and hepatocyte growth factor receptor (HGF receptor, proto-oncogene c-Met).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	51-54
25562798-3	2012	More recently the EML4-ALK fusion gene which occurs in 3-5% of NSCLC has been found to predict sensitivity to crizotinib an inhibitor of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase.	Crizotinib	110-120	EMAP like 4	Homo sapiens	18-22
25562798-3	2012	More recently the EML4-ALK fusion gene which occurs in 3-5% of NSCLC has been found to predict sensitivity to crizotinib an inhibitor of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	23-26
25562798-3	2012	More recently the EML4-ALK fusion gene which occurs in 3-5% of NSCLC has been found to predict sensitivity to crizotinib an inhibitor of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	141-167
25562798-3	2012	More recently the EML4-ALK fusion gene which occurs in 3-5% of NSCLC has been found to predict sensitivity to crizotinib an inhibitor of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	169-172
22473102-2	2012	Crizotinib, an orally bioavailable inhibitor of ALK, provides significant benefit for patients with ALK-positive (ALK+) NSCLC in association with characteristic, mostly mild, toxic effects, and this drug has been approved by the FDA for clinical use in this molecularly defined subgroup of lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	48-51
22473102-2	2012	Crizotinib, an orally bioavailable inhibitor of ALK, provides significant benefit for patients with ALK-positive (ALK+) NSCLC in association with characteristic, mostly mild, toxic effects, and this drug has been approved by the FDA for clinical use in this molecularly defined subgroup of lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	100-103
22473102-2	2012	Crizotinib, an orally bioavailable inhibitor of ALK, provides significant benefit for patients with ALK-positive (ALK+) NSCLC in association with characteristic, mostly mild, toxic effects, and this drug has been approved by the FDA for clinical use in this molecularly defined subgroup of lung cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	100-103
22155737-8	2012	Lastly, knockdown of Twist1 sensitizes ALK+ALCL cells to the growth inhibitory effect of PF-2341066 (Crizotinib ), an ALK inhibitor being used in clinical trials.	Crizotinib	101-111	twist family bHLH transcription factor 1	Homo sapiens	21-27
22155737-8	2012	Lastly, knockdown of Twist1 sensitizes ALK+ALCL cells to the growth inhibitory effect of PF-2341066 (Crizotinib ), an ALK inhibitor being used in clinical trials.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	39-42
22155737-8	2012	Lastly, knockdown of Twist1 sensitizes ALK+ALCL cells to the growth inhibitory effect of PF-2341066 (Crizotinib ), an ALK inhibitor being used in clinical trials.	Crizotinib	101-111	ALK receptor tyrosine kinase	Homo sapiens	118-121
22311682-3	2012	Crizotinib is a small molecule inhibitor of ALK kinase that has recently been approved by the FDA for the treatment of patients with ALK-positive NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	44-47
22311682-3	2012	Crizotinib is a small molecule inhibitor of ALK kinase that has recently been approved by the FDA for the treatment of patients with ALK-positive NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	133-136
22536569-1	2012	Crizotinib is a potent small-molecule inhibitor of ALK tyrosine kinase receptor (anaplastic lymphoma kinase; ALK) and hepatocyte growth factor receptor (HGF receptor, proto-oncogene c-Met).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	109-112
22536569-1	2012	Crizotinib is a potent small-molecule inhibitor of ALK tyrosine kinase receptor (anaplastic lymphoma kinase; ALK) and hepatocyte growth factor receptor (HGF receptor, proto-oncogene c-Met).	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	118-151
22536569-3	2012	Crizotinib has demonstrated preclinical and clinical activity against such malignancies through inhibition of ALK, and patients harboring ALK- rearranged NSCLC have demonstrated high response rates and prolonged progression-free survival in phase I and II studies.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	110-113
22536569-4	2012	In August 2011, crizotinib was approved for the treatment of advanced ALK-positive NSCLC.	Crizotinib	16-26	ALK receptor tyrosine kinase	Homo sapiens	70-73
22443113-7	2012	EXPERT OPINION: In a pivotal Phase I clinical trial, crizotinib (PF-02341066), a small-molecule ALK inhibitor, demonstrated impressive antitumor activity in the majority of NSCLC patients with ALK fusions.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	96-99
22443113-7	2012	EXPERT OPINION: In a pivotal Phase I clinical trial, crizotinib (PF-02341066), a small-molecule ALK inhibitor, demonstrated impressive antitumor activity in the majority of NSCLC patients with ALK fusions.	Crizotinib	53-63	ALK receptor tyrosine kinase	Homo sapiens	193-196
22443113-9	2012	If the results from these large international trials confirm the efficacy of crizotinib in the subset of patients, the next few years could see the treatment of advanced NSCLC patients with ALK fusions.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	190-193
22500682-6	2012	With the recent US approval of crizotinib, a multi-targeted ALK/MET kinase inhibitor, for the treatment of ALK-rearranged NSCLC, attention has turned to ROS1-rearranged tumors, especially NSCLC.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	60-63
22500682-6	2012	With the recent US approval of crizotinib, a multi-targeted ALK/MET kinase inhibitor, for the treatment of ALK-rearranged NSCLC, attention has turned to ROS1-rearranged tumors, especially NSCLC.	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	107-110
22500682-6	2012	With the recent US approval of crizotinib, a multi-targeted ALK/MET kinase inhibitor, for the treatment of ALK-rearranged NSCLC, attention has turned to ROS1-rearranged tumors, especially NSCLC.	Crizotinib	31-41	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	153-157
22215748-13	2012	Crizotinib shows in vitro activity and early evidence of clinical activity in ROS1-rearranged NSCLC.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	78-82
22235099-0	2012	Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	56-59
22215748-4	2012	In vitro studies assessed the responsiveness of cells with ROS1 rearrangement to the tyrosine kinase inhibitor crizotinib.	Crizotinib	111-121	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	59-63
22215748-5	2012	The clinical response of one patient with ROS1-rearranged NSCLC to crizotinib was investigated as part of an expanded phase I cohort.	Crizotinib	67-77	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	42-46
22215748-10	2012	The HCC78 ROS1-rearranged NSCLC cell line and 293 cells transfected with CD74-ROS1 showed evidence of sensitivity to crizotinib.	Crizotinib	117-127	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	10-14
22215748-10	2012	The HCC78 ROS1-rearranged NSCLC cell line and 293 cells transfected with CD74-ROS1 showed evidence of sensitivity to crizotinib.	Crizotinib	117-127	CD74 molecule	Homo sapiens	73-77
22215748-10	2012	The HCC78 ROS1-rearranged NSCLC cell line and 293 cells transfected with CD74-ROS1 showed evidence of sensitivity to crizotinib.	Crizotinib	117-127	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	78-82
22585997-4	2012	However, invasion and metastasis were reduced by concurrent inhibition of c-Met by PF-04217903 or PF-02341066 (crizotinib).	Crizotinib	111-121	met proto-oncogene	Mus musculus	74-79
22235099-1	2012	PURPOSE: Patients with anaplastic lymphoma kinase (ALK) gene rearrangements often manifest dramatic responses to crizotinib, a small-molecule ALK inhibitor.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	23-49
22235099-1	2012	PURPOSE: Patients with anaplastic lymphoma kinase (ALK) gene rearrangements often manifest dramatic responses to crizotinib, a small-molecule ALK inhibitor.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	51-54
22235099-1	2012	PURPOSE: Patients with anaplastic lymphoma kinase (ALK) gene rearrangements often manifest dramatic responses to crizotinib, a small-molecule ALK inhibitor.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	142-145
22235099-3	2012	This study aimed to define molecular mechanisms of resistance to crizotinib in patients with ALK(+) non-small cell lung cancer (NSCLC).	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	93-96
22235099-7	2012	A novel mutation in the ALK domain, encoding a G1269A amino acid substitution that confers resistance to crizotinib in vitro, was identified in two of these cases.	Crizotinib	105-115	ALK receptor tyrosine kinase	Homo sapiens	24-27
22235099-13	2012	CONCLUSIONS: Crizotinib resistance in ALK(+) NSCLC occurs through somatic kinase domain mutations, ALK gene fusion CNG, and emergence of separate oncogenic drivers.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	38-41
22235099-13	2012	CONCLUSIONS: Crizotinib resistance in ALK(+) NSCLC occurs through somatic kinase domain mutations, ALK gene fusion CNG, and emergence of separate oncogenic drivers.	Crizotinib	13-23	ALK receptor tyrosine kinase	Homo sapiens	99-102
22129595-0	2012	Pharmacokinetic/pharmacodynamic modeling of crizotinib for anaplastic lymphoma kinase inhibition and antitumor efficacy in human tumor xenograft mouse models.	Crizotinib	44-54	ALK receptor tyrosine kinase	Homo sapiens	59-85
22129595-1	2012	Crizotinib [Xalkori; PF02341066; (R)-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine] is an orally available dual inhibitor of anaplastic lymphoma kinase (ALK) and hepatocyte growth factor receptor.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	178-204
22129595-1	2012	Crizotinib [Xalkori; PF02341066; (R)-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine] is an orally available dual inhibitor of anaplastic lymphoma kinase (ALK) and hepatocyte growth factor receptor.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	206-209
22129595-1	2012	Crizotinib [Xalkori; PF02341066; (R)-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine] is an orally available dual inhibitor of anaplastic lymphoma kinase (ALK) and hepatocyte growth factor receptor.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	215-248
22129595-2	2012	The objectives of the present studies were to characterize: 1) the pharmacokinetic/pharmacodynamic relationship of crizotinib plasma concentrations to the inhibition of ALK phosphorylation in tumors, and 2) the relationship of ALK inhibition to antitumor efficacy in human tumor xenograft models.	Crizotinib	115-125	ALK receptor tyrosine kinase	Homo sapiens	169-172
22129595-8	2012	Furthermore, based on the observed clinical pharmacokinetic data coupled with the pharmacodynamic parameters obtained from the present nonclinical xenograft mouse model, >70% ALK inhibition was projected in patients with non-small-cell lung cancer who were administered the clinically recommended dosage of crizotinib, twice-daily doses of 250 mg (500 mg/day).	Crizotinib	310-320	anaplastic lymphoma kinase	Mus musculus	178-181
22129595-9	2012	The result suggests that crizotinib could sufficiently inhibit ALK phosphorylation for significant antitumor efficacy in patients.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	63-66
22323827-1	2012	Mutated anaplastic lymphoma kinase (ALK) drives the development of multiple tumor types, and ALK tyrosine kinase inhibitors such as crizotinib have been validated as targeted therapeutics.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	93-96
22277784-0	2012	Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers.	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	48-51
22334013-0	2012	Acquired resistance to the ALK inhibitor crizotinib in the absence of an ALK mutation.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	27-30
22655263-5	2012	Perhaps unsurprisingly, however, the appearance of clinical acquired resistance to crizotinib was observed early on in clinical testing, with the identification of several ALK secondary point mutations which diminish drug efficacy and which open the way for development of second-generation inhibitors.	Crizotinib	83-93	ALK receptor tyrosine kinase	Homo sapiens	172-175
22655263-6	2012	It is also emerging that acquired resistance to crizotinib may additionally occur through ALK-independent mechanisms, which still need to be elucidated in detail.	Crizotinib	48-58	ALK receptor tyrosine kinase	Homo sapiens	90-93
22277784-3	2012	Herein, we report findings from a series of lung cancer patients (n = 18) with acquired resistance to the ALK TKI crizotinib.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	106-109
22277784-5	2012	Next-generation ALK inhibitors, developed to overcome crizotinib resistance, had differing potencies against specific resistance mutations.	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	16-19
22277784-8	2012	These results highlight the unique features of TKI resistance in ALK-positive NSCLCs and provide the rationale for pursuing combinatorial therapeutics that are tailored to the precise resistance mechanisms identified in patients who relapse on crizotinib treatment.	Crizotinib	244-254	ALK receptor tyrosine kinase	Homo sapiens	65-68
22215903-5	2012	Although vemurafenib for B-Raf-mutated melanoma and crizotinib for non-small cell lung cancers with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements were developed rapidly and offer hope for individualized targeted therapies, the development of agents targeting a number of other pathways has been slower and less successful.	Crizotinib	52-62	EMAP like 4	Homo sapiens	100-148
22585869-3	2012	CLINICAL RELEVANCE: ROS1-positive NSCLC patients may benefit from crizotinib therapy.	Crizotinib	66-76	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	20-24
21854543-12	2012	Recently, crizotinib produced promising results in a subtype of lung cancers with ALK fusion.	Crizotinib	10-20	ALK receptor tyrosine kinase	Homo sapiens	82-85
22316363-1	2012	Crizotinib (Pfizer, CA, USA) is an oral small-molecule RTK inhibitor that targets ALK and MET, and potentially other RTKs.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	82-85
22316363-2	2012	Crizotinib was approved by the US FDA on 26 August 2011 for the treatment of ALK-rearranged non-small-cell lung cancer (NSCLC), as detected by ALK break-apart FISH assay.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	77-80
22316363-2	2012	Crizotinib was approved by the US FDA on 26 August 2011 for the treatment of ALK-rearranged non-small-cell lung cancer (NSCLC), as detected by ALK break-apart FISH assay.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	143-146
22474449-8	2012	The recent introduction of the small molecule ALK inhibitor, crizotinib, may provide a potential new therapeutic option for patients with this disease.	Crizotinib	61-71	ALK receptor tyrosine kinase	Homo sapiens	46-49
22215903-5	2012	Although vemurafenib for B-Raf-mutated melanoma and crizotinib for non-small cell lung cancers with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements were developed rapidly and offer hope for individualized targeted therapies, the development of agents targeting a number of other pathways has been slower and less successful.	Crizotinib	52-62	EMAP like 4	Homo sapiens	150-154
23301645-6	2012	Targeted inhibition of constitutively activated ALK kinase mediated by crizotinib in patients positive for ALK gene rearrangements resulted in remarkable treatment response (57%) with minimal toxicity.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	48-51
23788933-4	2012	Crizotinib is an oral inhibitor of ALK kinase activity, approved for the treatment of NSCLC patients with ALK gene rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	35-38
23788933-4	2012	Crizotinib is an oral inhibitor of ALK kinase activity, approved for the treatment of NSCLC patients with ALK gene rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	106-109
23788933-6	2012	The present paper gives an overview of literature reports on the role of crizotinib in the treatment of NSCLC patients harbouring a molecular defect in the ALK gene.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	156-159
23301645-6	2012	Targeted inhibition of constitutively activated ALK kinase mediated by crizotinib in patients positive for ALK gene rearrangements resulted in remarkable treatment response (57%) with minimal toxicity.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	107-110
21948233-5	2011	RESULTS: Here, we show that the resistance mutation, L1196M, as well as other crizotinib resistance mutations (F1174L and G1269S), are highly sensitive to the structurally unrelated ALK inhibitor TAE684.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	182-185
22286583-4	2012	At the moment, established personalized treatment approaches include treatment of patients with NSCLC and activating epidermal growth factor receptor (EGFR) mutations with the EGFR-directed tyrosine kinase inhibitors gefitinib or erlotinib, and treatment of NSCLC patients with genetic aberrations in the anaplastic lymphoma kinase (ALK) oncogene with the mesenchymal-epithelial transition factor (MET)/ALK inhibitor crizotinib.	Crizotinib	417-427	epidermal growth factor receptor	Homo sapiens	151-155
22286583-4	2012	At the moment, established personalized treatment approaches include treatment of patients with NSCLC and activating epidermal growth factor receptor (EGFR) mutations with the EGFR-directed tyrosine kinase inhibitors gefitinib or erlotinib, and treatment of NSCLC patients with genetic aberrations in the anaplastic lymphoma kinase (ALK) oncogene with the mesenchymal-epithelial transition factor (MET)/ALK inhibitor crizotinib.	Crizotinib	417-427	epidermal growth factor receptor	Homo sapiens	176-180
23226067-7	2012	More recently, the presence of a fusion gene, echinoderm microtubule-associated protein-like 4 - anaplastic lymphoma kinase (EML4-ALK), was identified as the driver mutation in yet another subgroup of patients, and subsequent studies have led to approval of crizotinib in this group of patients.	Crizotinib	258-268	EMAP like 4	Homo sapiens	125-129
23226067-7	2012	More recently, the presence of a fusion gene, echinoderm microtubule-associated protein-like 4 - anaplastic lymphoma kinase (EML4-ALK), was identified as the driver mutation in yet another subgroup of patients, and subsequent studies have led to approval of crizotinib in this group of patients.	Crizotinib	258-268	ALK receptor tyrosine kinase	Homo sapiens	130-133
22085382-3	2011	This has also paved the way for the integration of molecular analyses into early phase clinical trials, as demonstrated by the clinical development of crizotinib, effective in lung cancer harbouring Alk rearrangements.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	199-202
22989574-0	2012	Crizotinib for the treatment of ALK-rearranged non-small cell lung cancer: a success story to usher in the second decade of molecular targeted therapy in oncology.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	32-35
22989574-1	2012	Crizotinib, an ALK/MET/ROS1 inhibitor, was approved by the U.S. Food and Drug Administration for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) in August 2011, merely 4 years after the first publication of ALK-rearranged NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	15-18
22989574-1	2012	Crizotinib, an ALK/MET/ROS1 inhibitor, was approved by the U.S. Food and Drug Administration for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) in August 2011, merely 4 years after the first publication of ALK-rearranged NSCLC.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	23-27
22989574-1	2012	Crizotinib, an ALK/MET/ROS1 inhibitor, was approved by the U.S. Food and Drug Administration for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) in August 2011, merely 4 years after the first publication of ALK-rearranged NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	114-140
22989574-1	2012	Crizotinib, an ALK/MET/ROS1 inhibitor, was approved by the U.S. Food and Drug Administration for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) in August 2011, merely 4 years after the first publication of ALK-rearranged NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	142-145
22989574-1	2012	Crizotinib, an ALK/MET/ROS1 inhibitor, was approved by the U.S. Food and Drug Administration for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) in August 2011, merely 4 years after the first publication of ALK-rearranged NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	142-145
22989574-3	2012	Crizotinib continued to be developed as an ALK and MET inhibitor in other tumor types driven by alteration in ALK and MET.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	43-46
22989574-3	2012	Crizotinib continued to be developed as an ALK and MET inhibitor in other tumor types driven by alteration in ALK and MET.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	110-113
22989574-4	2012	Crizotinib has recently been shown to be an effective ROS1 inhibitor in ROS1-rearranged NSCLC, with potential future clinical applications in ROS1-rearranged tumors.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	54-58
22989574-4	2012	Crizotinib has recently been shown to be an effective ROS1 inhibitor in ROS1-rearranged NSCLC, with potential future clinical applications in ROS1-rearranged tumors.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	72-76
22989574-4	2012	Crizotinib has recently been shown to be an effective ROS1 inhibitor in ROS1-rearranged NSCLC, with potential future clinical applications in ROS1-rearranged tumors.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	72-76
22989574-6	2012	We review the past and future clinical development of crizotinib for ALK-rearranged NSCLC and the diagnostic assays to detect ALK-rearranged NSCLC.	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	69-72
21838707-0	2011	Activating ALK mutations found in neuroblastoma are inhibited by Crizotinib and NVP-TAE684.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	11-14
22072639-3	2011	Identification of ALK as an oncogenic driver in neuroblastoma suggests that crizotinib (PF-02341066), a dual-specific inhibitor of the ALK and Met tyrosine kinases, will be useful in treating this malignancy.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	18-21
22034911-0	2011	Crizotinib-resistant mutants of EML4-ALK identified through an accelerated mutagenesis screen.	Crizotinib	0-10	EMAP like 4	Homo sapiens	32-36
22034911-0	2011	Crizotinib-resistant mutants of EML4-ALK identified through an accelerated mutagenesis screen.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	37-40
22034911-2	2011	Crizotinib, a dual MET/ALK inhibitor, has demonstrated promising clinical activity in patients with non-small-cell lung cancer and inflammatory myofibroblastic tumors harboring ALK translocations.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	23-26
22034911-2	2011	Crizotinib, a dual MET/ALK inhibitor, has demonstrated promising clinical activity in patients with non-small-cell lung cancer and inflammatory myofibroblastic tumors harboring ALK translocations.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	177-180
22034911-4	2011	Here, this approach was used to discover an extensive set of ALK mutations that can confer resistance to crizotinib.	Crizotinib	105-115	ALK receptor tyrosine kinase	Homo sapiens	61-64
22034911-7	2011	In separate studies, we demonstrated that crizotinib has relatively modest potency in ALK-positive non-small-cell lung cancer cell lines.	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	86-89
22034911-8	2011	A more potent ALK inhibitor, TAE684, maintained substantial activity against mutations that conferred resistance to crizotinib.	Crizotinib	116-126	ALK receptor tyrosine kinase	Homo sapiens	14-17
22034911-9	2011	Our study identifies multiple novel mutations in ALK that may confer clinical resistance to crizotinib, suggests that crizotinib"s narrow selectivity window may underlie its susceptibility to such resistance and demonstrates that a more potent ALK inhibitor may be effective at overcoming resistance.	Crizotinib	92-102	ALK receptor tyrosine kinase	Homo sapiens	49-52
22034911-9	2011	Our study identifies multiple novel mutations in ALK that may confer clinical resistance to crizotinib, suggests that crizotinib"s narrow selectivity window may underlie its susceptibility to such resistance and demonstrates that a more potent ALK inhibitor may be effective at overcoming resistance.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	49-52
22034911-9	2011	Our study identifies multiple novel mutations in ALK that may confer clinical resistance to crizotinib, suggests that crizotinib"s narrow selectivity window may underlie its susceptibility to such resistance and demonstrates that a more potent ALK inhibitor may be effective at overcoming resistance.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	244-247
22157554-1	2011	Crizotinib was recently approved by the US FDA for the treatment of advanced non-small cell lung cancer (NSCLC) harboring the ALK (anaplastic lymphoma kinase) gene rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	126-129
22088989-1	2011	Crizotinib, a dual MET/ALK inhibitor, is now in advanced clinical development for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	23-26
22088989-1	2011	Crizotinib, a dual MET/ALK inhibitor, is now in advanced clinical development for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	99-125
22088989-1	2011	Crizotinib, a dual MET/ALK inhibitor, is now in advanced clinical development for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	127-130
22072639-7	2011	Biochemical analyses revealed that this reduced susceptibility of F1174L-mutated ALK to crizotinib inhibition resulted from an increased adenosine triphosphate-binding affinity (as also seen in acquired resistance to epidermal growth factor receptor inhibitors).	Crizotinib	88-98	ALK receptor tyrosine kinase	Homo sapiens	81-84
22010214-3	2011	The ALK tyrosine kinase inhibitor crizotinib has demonstrated clinical efficacy in ALK-rearranged NSCLC patients and was recently approved by the U.S. Food and Drug Administration.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	4-7
22010214-3	2011	The ALK tyrosine kinase inhibitor crizotinib has demonstrated clinical efficacy in ALK-rearranged NSCLC patients and was recently approved by the U.S. Food and Drug Administration.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	83-86
22010214-4	2011	Crizotinib is currently under additional phase III clinical development as both initial and second-line therapy for advanced ALK-rearranged NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	125-128
22072639-3	2011	Identification of ALK as an oncogenic driver in neuroblastoma suggests that crizotinib (PF-02341066), a dual-specific inhibitor of the ALK and Met tyrosine kinases, will be useful in treating this malignancy.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	135-138
22072639-4	2011	Here, we assessed the ability of crizotinib to inhibit proliferation of neuroblastoma cell lines and xenografts expressing mutated or wild-type ALK.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	144-147
22072639-5	2011	Crizotinib inhibited proliferation of cell lines expressing either R1275Q-mutated ALK or amplified wild-type ALK.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	82-85
22072639-5	2011	Crizotinib inhibited proliferation of cell lines expressing either R1275Q-mutated ALK or amplified wild-type ALK.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	109-112
22072639-6	2011	In contrast, cell lines harboring F1174L-mutated ALK were relatively resistant to crizotinib.	Crizotinib	82-92	ALK receptor tyrosine kinase	Homo sapiens	49-52
22084642-4	2011	Cells with abnormal ALK signaling are sensitive to ALK inhibitors such as crizotinib.	Crizotinib	74-84	ALK receptor tyrosine kinase	Homo sapiens	20-23
22082640-1	2011	The discovery of anaplastic lymphoma kinase (ALK) rearrangements in a subset of patients with nonsmall- cell lung cancer (NSCLC) and its potential blockage by specific inhibitors such as crizotinib has been one of the latest advances in the treatment of this disease.	Crizotinib	187-197	ALK receptor tyrosine kinase	Homo sapiens	17-43
22082640-1	2011	The discovery of anaplastic lymphoma kinase (ALK) rearrangements in a subset of patients with nonsmall- cell lung cancer (NSCLC) and its potential blockage by specific inhibitors such as crizotinib has been one of the latest advances in the treatment of this disease.	Crizotinib	187-197	ALK receptor tyrosine kinase	Homo sapiens	45-48
22050016-6	2011	Recently, Phase I-II trial results of crizotinib, a potent dual c-MET and ALK inhibitor, demonstrated its dramatic efficacy in ALK-positive patients with advanced NSCLC.	Crizotinib	38-48	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	64-69
22050016-6	2011	Recently, Phase I-II trial results of crizotinib, a potent dual c-MET and ALK inhibitor, demonstrated its dramatic efficacy in ALK-positive patients with advanced NSCLC.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	74-77
22050016-6	2011	Recently, Phase I-II trial results of crizotinib, a potent dual c-MET and ALK inhibitor, demonstrated its dramatic efficacy in ALK-positive patients with advanced NSCLC.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	127-130
22084642-4	2011	Cells with abnormal ALK signaling are sensitive to ALK inhibitors such as crizotinib.	Crizotinib	74-84	ALK receptor tyrosine kinase	Homo sapiens	51-54
22084642-5	2011	This review will highlight the discovery of the fusion between echinoderm microtubule-associated protein-like 4 (EML4) and ALK as an oncogenic driver, recognition of other ALK gene rearrangements in NSCLC, and the confirmation that crizotinib is an effective treatment for patients with ALK-positive NSCLC.	Crizotinib	232-242	EMAP like 4	Homo sapiens	63-111
21716144-4	2011	RESULTS: Inhibition of MET signaling by crizotinib or by RNA interference-mediated MET depletion resulted in the induction of apoptosis accompanied by inhibition of AKT and extracellular signal-regulated kinase phosphorylation in lung cancer cells with MET amplification but not in cells with a MET mutation or in those without amplification or mutation of MET.	Crizotinib	40-50	AKT serine/threonine kinase 1	Homo sapiens	165-168
22084642-6	2011	Work is underway to further define the role for crizotinib in the treatment of ALK-positive lung cancer and other cancers and to investigate the molecular mechanisms for resistance to ALK inhibition with crizotinib.	Crizotinib	48-58	ALK receptor tyrosine kinase	Homo sapiens	79-82
21587085-1	2011	INTRODUCTION: Accurate determination of ALK rearrangement is important in lung cancer patients, especially in determining their eligibility for crizotinib therapy.	Crizotinib	144-154	ALK receptor tyrosine kinase	Homo sapiens	40-43
21945349-5	2011	Indeed, F1174L has shown more potent transforming activity in vivo than the second most common activating mutation, R1275Q, and is responsible for innate and acquired resistance to crizotinib, a clinically relevant ALK inhibitor that will soon be commercially available.	Crizotinib	181-191	ALK receptor tyrosine kinase	Homo sapiens	215-218
21791641-1	2011	Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI), including crizotinib, are effective treatments in preclinical models and in cancer patients with ALK-translocated cancers.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	0-26
21791641-1	2011	Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI), including crizotinib, are effective treatments in preclinical models and in cancer patients with ALK-translocated cancers.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	28-31
21791641-1	2011	Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI), including crizotinib, are effective treatments in preclinical models and in cancer patients with ALK-translocated cancers.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	164-167
21791641-3	2011	Here we report two mechanisms of ALK TKI resistance identified from a crizotinib-treated non-small cell lung cancer (NSCLC) patient and in a cell line generated from the resistant tumor (DFCI076) as well as from studying a resistant version of the ALK TKI (TAE684)-sensitive H3122 cell line.	Crizotinib	70-80	ALK receptor tyrosine kinase	Homo sapiens	33-36
21791641-4	2011	The crizotinib-resistant DFCI076 cell line harbored a unique L1152R ALK secondary mutation and was also resistant to the structurally unrelated ALK TKI TAE684.	Crizotinib	4-14	ALK receptor tyrosine kinase	Homo sapiens	68-71
21791641-4	2011	The crizotinib-resistant DFCI076 cell line harbored a unique L1152R ALK secondary mutation and was also resistant to the structurally unrelated ALK TKI TAE684.	Crizotinib	4-14	ALK receptor tyrosine kinase	Homo sapiens	144-147
21764800-4	2011	Crizotinib (PF-2341066) is a novel adenosine triphosphate-competitive c-MET kinase inhibitor with antitumor activity in a range of tumor models.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	70-75
21764800-4	2011	Crizotinib (PF-2341066) is a novel adenosine triphosphate-competitive c-MET kinase inhibitor with antitumor activity in a range of tumor models.	Crizotinib	12-22	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	70-75
21764800-5	2011	The aim of this study was to investigate the utility of PET of glucose metabolism and cell proliferation to monitor tumor response to crizotinib in 2 cell lines with aberrant c-MET signaling.	Crizotinib	134-144	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	175-180
21933749-0	2011	Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis.	Crizotinib	10-20	ALK receptor tyrosine kinase	Homo sapiens	105-108
21933749-2	2011	In a recent phase 1 clinical trial, the ALK tyrosine-kinase inhibitor (TKI) crizotinib showed marked antitumour activity in patients with advanced, ALK-positive NSCLC.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	40-43
21933749-2	2011	In a recent phase 1 clinical trial, the ALK tyrosine-kinase inhibitor (TKI) crizotinib showed marked antitumour activity in patients with advanced, ALK-positive NSCLC.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	148-151
21933749-7	2011	FINDINGS: Among 82 ALK-positive patients who were given crizotinib, median overall survival from initiation of crizotinib has not been reached (95% CI 17 months to not reached); 1-year overall survival was 74% (95% CI 63-82), and 2-year overall survival was 54% (40-66).	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	19-22
21933749-11	2011	INTERPRETATION: In patients with advanced, ALK-positive NSCLC, crizotinib therapy is associated with improved survival compared with that of crizotinib-naive controls.	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	43-46
21812414-0	2011	Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK).	Crizotinib	31-41	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	140-145
21812414-0	2011	Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK).	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	158-184
21812414-0	2011	Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK).	Crizotinib	31-41	ALK receptor tyrosine kinase	Homo sapiens	186-189
21812414-0	2011	Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK).	Crizotinib	43-54	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	140-145
21812414-0	2011	Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK).	Crizotinib	43-54	ALK receptor tyrosine kinase	Homo sapiens	158-184
21812414-0	2011	Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK).	Crizotinib	43-54	ALK receptor tyrosine kinase	Homo sapiens	186-189
21812414-5	2011	Further optimization of the lead series generated the clinical candidate crizotinib (PF-02341066), which demonstrated potent in vitro and in vivo c-MET kinase and ALK inhibition, effective tumor growth inhibition, and good pharmaceutical properties.	Crizotinib	73-83	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	146-151
21812414-5	2011	Further optimization of the lead series generated the clinical candidate crizotinib (PF-02341066), which demonstrated potent in vitro and in vivo c-MET kinase and ALK inhibition, effective tumor growth inhibition, and good pharmaceutical properties.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	163-166
21423210-6	2011	Lateral signaling is blocked by two selective c-Met tyrosine kinase inhibitors (TKIs), PF2341066 and SU11274, or with gefitinib, an EGFR TKI, suggesting kinase activity of both receptors is required for this effect.	Crizotinib	87-96	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	46-51
21767331-0	2011	Favorable response to crizotinib in three patients with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion-type oncogene-positive non-small cell lung cancer.	Crizotinib	22-32	EMAP like 4	Homo sapiens	56-104
21767331-3	2011	A clinical trial of crizotinib (PF-02341066) sponsored by Pfizer has proven this oncogene addiction in humans by demonstrating a high response rate to inhibition of ALK kinase activity.	Crizotinib	20-30	ALK receptor tyrosine kinase	Homo sapiens	165-168
21823889-1	2011	Crizotinib is an oral small-molecule inhibitor of ALK and c-Met tyrosine kinases that is being developed by Pfizer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	50-53
21823889-1	2011	Crizotinib is an oral small-molecule inhibitor of ALK and c-Met tyrosine kinases that is being developed by Pfizer.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	58-63
21823889-3	2011	Most of the available clinical data with crizotinib are in patients with tumors that have an activated ALK, and the drug has shown very promising clinical benefit in these patients.	Crizotinib	41-51	ALK receptor tyrosine kinase	Homo sapiens	103-106
21764800-8	2011	RESULTS: Treatment of c-MET-amplified GTL-16 xenografts with 50 mg/kg crizotinib caused tumor regression that was associated with a slow reduction in (18)F-FDG uptake (P < 0.05, day 13) and reduced expression of the glucose transporter 1, GLUT-1.	Crizotinib	70-80	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	22-27
21764800-8	2011	RESULTS: Treatment of c-MET-amplified GTL-16 xenografts with 50 mg/kg crizotinib caused tumor regression that was associated with a slow reduction in (18)F-FDG uptake (P < 0.05, day 13) and reduced expression of the glucose transporter 1, GLUT-1.	Crizotinib	70-80	solute carrier family 2 member 1	Homo sapiens	242-248
21764800-10	2011	These findings were confirmed in vitro, where treatment of U87MG cells with 1 muM crizotinib had no demonstrable effect on glucose uptake.	Crizotinib	82-92	latexin	Homo sapiens	78-81
21888258-6	2011	A definitive study randomizing patients with ALK-mutant lung cancer to crizotinib (also known as PF-02341066 or 1066) versus standard therapy has recently completed enrollment.Taken together, these data describe a trajectory of research progress from basic discovery science to real-world implementation that should serve as a model for future integration of preclinical and clinical therapeutic research.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	45-48
21622718-5	2011	RESULTS: Combining the c-Met inhibitor PF2341066 with the EGFR inhibitor gefitinib abrogated HNSCC cell proliferation, invasion, and wound healing significantly more than inhibition of each pathway alone in HNSCC cell lines.	Crizotinib	39-48	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	23-28
21777762-6	2011	So, the EML4 - ALK translocation is accessible to a treatment by crizotinib, with response rate around 60-70%.	Crizotinib	65-75	EMAP like 4	Homo sapiens	8-12
21777762-6	2011	So, the EML4 - ALK translocation is accessible to a treatment by crizotinib, with response rate around 60-70%.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	15-18
21777766-5	2011	Recently, the ALK-AML4 translocation has been found in approximately 5% of NSCLC, accessible to a specified targeted therapy (crizotinib) with response rate around 60%.	Crizotinib	126-136	ALK receptor tyrosine kinase	Homo sapiens	14-17
21904575-7	2011	Crizotinib (PF02341066), an ALK TKI, has shown impressive activity against ALK translocated NSCLC in an expanded cohort of a phase I trial (NCT00585195).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	28-31
21430068-1	2011	PURPOSE: The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been used in patients with lung cancer or inflammatory myofibroblastic tumor (IMT), both types harboring ALK fusions.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	13-39
21430068-1	2011	PURPOSE: The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been used in patients with lung cancer or inflammatory myofibroblastic tumor (IMT), both types harboring ALK fusions.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	41-44
21430068-1	2011	PURPOSE: The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been used in patients with lung cancer or inflammatory myofibroblastic tumor (IMT), both types harboring ALK fusions.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	176-179
21502504-0	2011	Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK.	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	123-126
21502504-3	2011	In a pivotal phase 1 clinical trial, the ALK tyrosine kinase inhibitor (TKI) crizotinib (PF-02341066) demonstrated impressive antitumor activity in the majority of patients with NSCLC harboring ALK fusions.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	41-44
21502504-3	2011	In a pivotal phase 1 clinical trial, the ALK tyrosine kinase inhibitor (TKI) crizotinib (PF-02341066) demonstrated impressive antitumor activity in the majority of patients with NSCLC harboring ALK fusions.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	194-197
21502504-6	2011	We found that cells resistant to intermediate doses of crizotinib developed amplification of the EML4-ALK gene.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	102-105
21502504-11	2011	Thus, we have developed a model of acquired resistance to ALK inhibitors and have shown that second-generation ALK TKIs or Hsp90 inhibitors are effective in treating crizotinib-resistant tumors harboring secondary gatekeeper mutations.	Crizotinib	166-176	ALK receptor tyrosine kinase	Homo sapiens	58-61
21502504-11	2011	Thus, we have developed a model of acquired resistance to ALK inhibitors and have shown that second-generation ALK TKIs or Hsp90 inhibitors are effective in treating crizotinib-resistant tumors harboring secondary gatekeeper mutations.	Crizotinib	166-176	ALK receptor tyrosine kinase	Homo sapiens	111-114
21623265-0	2011	Activity of crizotinib (PF02341066), a dual mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	88-114
21623265-0	2011	Activity of crizotinib (PF02341066), a dual mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	116-119
21623265-1	2011	Crizotinib is a dual MET and ALK inhibitor.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	29-32
21623265-2	2011	Currently, clinical development of crizotinib is focused primarily on ALK rearranged non-small cell lung cancer (NSCLC).	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	70-73
21623265-3	2011	Here we report an NSCLC patient with de novo MET amplification but no ALK rearrangement who achieved a rapid and durable response to crizotinib indicating is also a bona fide MET inhibitor.	Crizotinib	133-143	ALK receptor tyrosine kinase	Homo sapiens	70-73
21515061-3	2011	Above all, crizotinib (PF-02341066) has been under clinical trial, and its therapeutic efficacy of inhibiting ALK in NSCLC has been reported.	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	110-113
21904575-7	2011	Crizotinib (PF02341066), an ALK TKI, has shown impressive activity against ALK translocated NSCLC in an expanded cohort of a phase I trial (NCT00585195).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	75-78
21208134-5	2011	AREAS COVERED: This paper discusses the clinical and therapeutic importance of ALK mutations in NSCLC and the early clinical results of a Phase I study assessing crizotinib in patients with ALK mutations.	Crizotinib	162-172	ALK receptor tyrosine kinase	Homo sapiens	190-193
21504625-6	2011	Early-phase clinical studies with Crizotinib, an ALK inhibitor, in NSCLC harboring EML4-ALK have demonstrated promising activity with high response rate and prolonged progression-free survival.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	49-52
21504625-6	2011	Early-phase clinical studies with Crizotinib, an ALK inhibitor, in NSCLC harboring EML4-ALK have demonstrated promising activity with high response rate and prolonged progression-free survival.	Crizotinib	34-44	EMAP like 4	Homo sapiens	83-87
21504625-6	2011	Early-phase clinical studies with Crizotinib, an ALK inhibitor, in NSCLC harboring EML4-ALK have demonstrated promising activity with high response rate and prolonged progression-free survival.	Crizotinib	34-44	ALK receptor tyrosine kinase	Homo sapiens	88-91
21288922-4	2011	The aberrant activation of ALK signaling leads to "oncogene addiction" and marked sensitivity to ALK inhibitors such as crizotinib (PF-02341066).	Crizotinib	120-130	ALK receptor tyrosine kinase	Homo sapiens	27-30
21288922-4	2011	The aberrant activation of ALK signaling leads to "oncogene addiction" and marked sensitivity to ALK inhibitors such as crizotinib (PF-02341066).	Crizotinib	120-130	ALK receptor tyrosine kinase	Homo sapiens	97-100
21288922-4	2011	The aberrant activation of ALK signaling leads to "oncogene addiction" and marked sensitivity to ALK inhibitors such as crizotinib (PF-02341066).	Crizotinib	132-143	ALK receptor tyrosine kinase	Homo sapiens	27-30
21288922-4	2011	The aberrant activation of ALK signaling leads to "oncogene addiction" and marked sensitivity to ALK inhibitors such as crizotinib (PF-02341066).	Crizotinib	132-143	ALK receptor tyrosine kinase	Homo sapiens	97-100
21475126-3	2011	A small molecule ALK inhibitor, crizotinib, may now be on the verge of approval by the US Food and Drug Administration for the treatment of ALK-rearranged lung cancer.	Crizotinib	32-42	ALK receptor tyrosine kinase	Homo sapiens	17-20
21475126-3	2011	A small molecule ALK inhibitor, crizotinib, may now be on the verge of approval by the US Food and Drug Administration for the treatment of ALK-rearranged lung cancer.	Crizotinib	32-42	ALK receptor tyrosine kinase	Homo sapiens	140-143
21208134-7	2011	Further clinical studies are needed in order to assess if crizotinib, an ALK inhibitor, is able to increase the efficacy of the conventional chemotherapy in this disease subset.	Crizotinib	58-68	ALK receptor tyrosine kinase	Homo sapiens	73-76
26412935-0	2011	Crizotinib (PF02341066) as a ALK /MET inhibitor- Special Emphasis as a Therapeutic Drug Against Lung Cancer.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	29-32
26412935-4	2011	In a phase I trial, EML4-ALK patients were selected to determine the response to a potent small molecule tyrosine kinase inhibitor crizotinib (previously identified as PF02341066).	Crizotinib	131-141	EMAP like 4	Homo sapiens	20-24
26412935-4	2011	In a phase I trial, EML4-ALK patients were selected to determine the response to a potent small molecule tyrosine kinase inhibitor crizotinib (previously identified as PF02341066).	Crizotinib	131-141	ALK receptor tyrosine kinase	Homo sapiens	25-28
21030459-1	2010	The ALK kinase inhibitor crizotinib (PF-02341066) is clinically effective in patients with ALK-translocated cancers, but its efficacy will ultimately be limited by acquired drug resistance.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	4-7
21428883-4	2011	In particular, in metastatic adenocarcinoma with an EML4-ALK fusion oncogene, crizotinib (a selective, ATP-competitive, small molecule, orally bioavailable inhibitor of the ALK and MET/HGF receptor tyrosine kinases), led to a response rate of 64%, which is similar to the results achieved in chronic myeloid leukemia and GIST with imatinib.	Crizotinib	78-88	EMAP like 4	Homo sapiens	52-56
21428883-4	2011	In particular, in metastatic adenocarcinoma with an EML4-ALK fusion oncogene, crizotinib (a selective, ATP-competitive, small molecule, orally bioavailable inhibitor of the ALK and MET/HGF receptor tyrosine kinases), led to a response rate of 64%, which is similar to the results achieved in chronic myeloid leukemia and GIST with imatinib.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	57-60
21428883-4	2011	In particular, in metastatic adenocarcinoma with an EML4-ALK fusion oncogene, crizotinib (a selective, ATP-competitive, small molecule, orally bioavailable inhibitor of the ALK and MET/HGF receptor tyrosine kinases), led to a response rate of 64%, which is similar to the results achieved in chronic myeloid leukemia and GIST with imatinib.	Crizotinib	78-88	ALK receptor tyrosine kinase	Homo sapiens	173-176
21428883-4	2011	In particular, in metastatic adenocarcinoma with an EML4-ALK fusion oncogene, crizotinib (a selective, ATP-competitive, small molecule, orally bioavailable inhibitor of the ALK and MET/HGF receptor tyrosine kinases), led to a response rate of 64%, which is similar to the results achieved in chronic myeloid leukemia and GIST with imatinib.	Crizotinib	78-88	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	185-197
22162641-0	2011	Crizotinib: a novel and first-in-class multitargeted tyrosine kinase inhibitor for the treatment of anaplastic lymphoma kinase rearranged non-small cell lung cancer and beyond.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	100-126
22162641-4	2011	Crizotinib, a mesenchymal-epithelial transition (MET)/ALK multi-targeted receptor tyrosine kinase inhibitor went into early Phase I clinical development in 2007.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	54-57
22162641-5	2011	Using the knowledge that NSCLC patients with activating EGFR mutations benefited from EGFR tyrosine kinase inhibitors, crizotinib was rapidly and successfully developed as an inhibitor in ALK-rearranged NSCLC, based on a break apart fluorescence in situ hybridization assay, developed by two of the crizotinib Phase I sites.	Crizotinib	119-129	epidermal growth factor receptor	Homo sapiens	56-60
22162641-5	2011	Using the knowledge that NSCLC patients with activating EGFR mutations benefited from EGFR tyrosine kinase inhibitors, crizotinib was rapidly and successfully developed as an inhibitor in ALK-rearranged NSCLC, based on a break apart fluorescence in situ hybridization assay, developed by two of the crizotinib Phase I sites.	Crizotinib	119-129	epidermal growth factor receptor	Homo sapiens	86-90
22162641-5	2011	Using the knowledge that NSCLC patients with activating EGFR mutations benefited from EGFR tyrosine kinase inhibitors, crizotinib was rapidly and successfully developed as an inhibitor in ALK-rearranged NSCLC, based on a break apart fluorescence in situ hybridization assay, developed by two of the crizotinib Phase I sites.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	188-191
22162641-6	2011	It cumulated in the conditional approval of crizotinib by the US Food and Drug Administration on August 26, 2011 for the treatment of ALK-rearranged NSCLC.	Crizotinib	44-54	ALK receptor tyrosine kinase	Homo sapiens	134-137
22162641-10	2011	It took an unprecedented four years from the discovery of ALK rearrangement in NSCLC to the approval of crizotinib, the first ever ALK inhibitor, for the treatment of ALK-rearranged NSCLC.	Crizotinib	104-114	ALK receptor tyrosine kinase	Homo sapiens	131-134
22162641-10	2011	It took an unprecedented four years from the discovery of ALK rearrangement in NSCLC to the approval of crizotinib, the first ever ALK inhibitor, for the treatment of ALK-rearranged NSCLC.	Crizotinib	104-114	ALK receptor tyrosine kinase	Homo sapiens	131-134
21785682-6	2011	Anaplastic lymphoma kinase (ALK) fusion protein detection and molecular histology classification are promising candidate predictors for clinical benefit from crizotinib and pemetrexed, respectively.	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	0-26
21785682-6	2011	Anaplastic lymphoma kinase (ALK) fusion protein detection and molecular histology classification are promising candidate predictors for clinical benefit from crizotinib and pemetrexed, respectively.	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	28-31
22443647-4	2011	The monoclonal antibody to EGFR, cetuximab, improves survival in patients with metastatic NSCLC, and the inhibitor of the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion protein, crizotinib, has resulted in an unprecedented overall survival advantage in patients harboring the EML4-ALK translocation.	Crizotinib	225-235	epidermal growth factor receptor	Homo sapiens	27-31
21030459-1	2010	The ALK kinase inhibitor crizotinib (PF-02341066) is clinically effective in patients with ALK-translocated cancers, but its efficacy will ultimately be limited by acquired drug resistance.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	91-94
21030459-1	2010	The ALK kinase inhibitor crizotinib (PF-02341066) is clinically effective in patients with ALK-translocated cancers, but its efficacy will ultimately be limited by acquired drug resistance.	Crizotinib	37-48	ALK receptor tyrosine kinase	Homo sapiens	4-7
21030459-1	2010	The ALK kinase inhibitor crizotinib (PF-02341066) is clinically effective in patients with ALK-translocated cancers, but its efficacy will ultimately be limited by acquired drug resistance.	Crizotinib	37-48	ALK receptor tyrosine kinase	Homo sapiens	91-94
21030459-2	2010	Here we report the identification of a secondary mutation in ALK, F1174L, as one cause of crizotinib resistance in a patient with an inflammatory myofibroblastic tumor (IMT) harboring a RANBP2-ALK translocation who progressed while on crizotinib therapy.	Crizotinib	90-100	ALK receptor tyrosine kinase	Homo sapiens	61-64
21030459-2	2010	Here we report the identification of a secondary mutation in ALK, F1174L, as one cause of crizotinib resistance in a patient with an inflammatory myofibroblastic tumor (IMT) harboring a RANBP2-ALK translocation who progressed while on crizotinib therapy.	Crizotinib	90-100	RAN binding protein 2	Homo sapiens	186-192
21030459-2	2010	Here we report the identification of a secondary mutation in ALK, F1174L, as one cause of crizotinib resistance in a patient with an inflammatory myofibroblastic tumor (IMT) harboring a RANBP2-ALK translocation who progressed while on crizotinib therapy.	Crizotinib	90-100	ALK receptor tyrosine kinase	Homo sapiens	193-196
21030459-2	2010	Here we report the identification of a secondary mutation in ALK, F1174L, as one cause of crizotinib resistance in a patient with an inflammatory myofibroblastic tumor (IMT) harboring a RANBP2-ALK translocation who progressed while on crizotinib therapy.	Crizotinib	235-245	ALK receptor tyrosine kinase	Homo sapiens	61-64
21030459-4	2010	Furthermore, the F1174L mutation inhibits crizotinib-mediated downregulation of ALK signaling and blocks apoptosis in RANBP2-ALK Ba/F3 cells.	Crizotinib	42-52	anaplastic lymphoma kinase	Mus musculus	80-83
21030459-4	2010	Furthermore, the F1174L mutation inhibits crizotinib-mediated downregulation of ALK signaling and blocks apoptosis in RANBP2-ALK Ba/F3 cells.	Crizotinib	42-52	RAN binding protein 2	Mus musculus	118-124
21030459-4	2010	Furthermore, the F1174L mutation inhibits crizotinib-mediated downregulation of ALK signaling and blocks apoptosis in RANBP2-ALK Ba/F3 cells.	Crizotinib	42-52	anaplastic lymphoma kinase	Mus musculus	125-128
21154129-0	2010	Crizotinib, a small-molecule dual inhibitor of the c-Met and ALK receptor tyrosine kinases.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	51-56
21220230-5	2010	The identification of the gene of fusion EML4-ALK in lung adenocarcinoma, and its inhibition by the crizotinib, constitute a considerable progress for 5% of patients with this disease.	Crizotinib	100-110	EMAP like 4	Homo sapiens	41-45
21220230-5	2010	The identification of the gene of fusion EML4-ALK in lung adenocarcinoma, and its inhibition by the crizotinib, constitute a considerable progress for 5% of patients with this disease.	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	46-49
21156280-3	2010	Now, crizotinib, an oral ALK inhibitor, is demonstrated to provide dramatic clinical benefit with little toxicity in patients having such advanced NSCLC, and a mechanism of clinical resistance to crizotinib is identified.	Crizotinib	5-15	ALK receptor tyrosine kinase	Homo sapiens	25-28
21154129-0	2010	Crizotinib, a small-molecule dual inhibitor of the c-Met and ALK receptor tyrosine kinases.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	61-64
21154129-1	2010	Crizotinib (PF-02341066), under development by Pfizer, is an orally bioavailable, ATP-competitive, small-molecule inhibitor of the receptor tyrosine kinases (RTKs) c-Met (also known as hepatocyte growth factor receptor) and anaplastic lymphoma kinase (ALK), for the potential treatment of cancers dependent on these oncogenic kinases for growth and survival.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	164-169
21154129-1	2010	Crizotinib (PF-02341066), under development by Pfizer, is an orally bioavailable, ATP-competitive, small-molecule inhibitor of the receptor tyrosine kinases (RTKs) c-Met (also known as hepatocyte growth factor receptor) and anaplastic lymphoma kinase (ALK), for the potential treatment of cancers dependent on these oncogenic kinases for growth and survival.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	185-218
21154129-1	2010	Crizotinib (PF-02341066), under development by Pfizer, is an orally bioavailable, ATP-competitive, small-molecule inhibitor of the receptor tyrosine kinases (RTKs) c-Met (also known as hepatocyte growth factor receptor) and anaplastic lymphoma kinase (ALK), for the potential treatment of cancers dependent on these oncogenic kinases for growth and survival.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	224-250
21154129-1	2010	Crizotinib (PF-02341066), under development by Pfizer, is an orally bioavailable, ATP-competitive, small-molecule inhibitor of the receptor tyrosine kinases (RTKs) c-Met (also known as hepatocyte growth factor receptor) and anaplastic lymphoma kinase (ALK), for the potential treatment of cancers dependent on these oncogenic kinases for growth and survival.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	252-255
21154129-1	2010	Crizotinib (PF-02341066), under development by Pfizer, is an orally bioavailable, ATP-competitive, small-molecule inhibitor of the receptor tyrosine kinases (RTKs) c-Met (also known as hepatocyte growth factor receptor) and anaplastic lymphoma kinase (ALK), for the potential treatment of cancers dependent on these oncogenic kinases for growth and survival.	Crizotinib	12-23	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	164-169
21154129-1	2010	Crizotinib (PF-02341066), under development by Pfizer, is an orally bioavailable, ATP-competitive, small-molecule inhibitor of the receptor tyrosine kinases (RTKs) c-Met (also known as hepatocyte growth factor receptor) and anaplastic lymphoma kinase (ALK), for the potential treatment of cancers dependent on these oncogenic kinases for growth and survival.	Crizotinib	12-23	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	185-218
21154129-1	2010	Crizotinib (PF-02341066), under development by Pfizer, is an orally bioavailable, ATP-competitive, small-molecule inhibitor of the receptor tyrosine kinases (RTKs) c-Met (also known as hepatocyte growth factor receptor) and anaplastic lymphoma kinase (ALK), for the potential treatment of cancers dependent on these oncogenic kinases for growth and survival.	Crizotinib	12-23	ALK receptor tyrosine kinase	Homo sapiens	224-250
21154129-1	2010	Crizotinib (PF-02341066), under development by Pfizer, is an orally bioavailable, ATP-competitive, small-molecule inhibitor of the receptor tyrosine kinases (RTKs) c-Met (also known as hepatocyte growth factor receptor) and anaplastic lymphoma kinase (ALK), for the potential treatment of cancers dependent on these oncogenic kinases for growth and survival.	Crizotinib	12-23	ALK receptor tyrosine kinase	Homo sapiens	252-255
21154129-2	2010	Since the first published characterizations of crizotinib only a few years ago, the drug has been extensively validated as a highly specific inhibitor of c-Met and ALK among > 120 different RTKs surveyed.	Crizotinib	47-57	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	154-159
21154129-2	2010	Since the first published characterizations of crizotinib only a few years ago, the drug has been extensively validated as a highly specific inhibitor of c-Met and ALK among > 120 different RTKs surveyed.	Crizotinib	47-57	ALK receptor tyrosine kinase	Homo sapiens	164-167
21154129-3	2010	In preclinical tumor xenograft studies, crizotinib inhibited the growth and survival of cell lines dependent upon c-Met or ALK enzymatic activity.	Crizotinib	40-50	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	114-119
21154129-3	2010	In preclinical tumor xenograft studies, crizotinib inhibited the growth and survival of cell lines dependent upon c-Met or ALK enzymatic activity.	Crizotinib	40-50	ALK receptor tyrosine kinase	Homo sapiens	123-126
21154129-4	2010	Crizotinib has been particularly effective against anaplastic large cell lymphoma and non-small cell lung cancer (NSCLC) cell lines that harbor ALK translocations resulting in expression of oncogenic ALK fusion proteins.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	144-147
21154129-4	2010	Crizotinib has been particularly effective against anaplastic large cell lymphoma and non-small cell lung cancer (NSCLC) cell lines that harbor ALK translocations resulting in expression of oncogenic ALK fusion proteins.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	200-203
21154129-5	2010	During early-stage clinical testing, crizotinib was well tolerated and produced dramatic antitumor activity in patients with ALK-rearranged NSCLC.	Crizotinib	37-47	ALK receptor tyrosine kinase	Homo sapiens	125-128
21154129-7	2010	Thus, in the future, crizotinib is expected to become a highly used therapeutic for the treatment of ALK-rearranged tumors.	Crizotinib	21-31	ALK receptor tyrosine kinase	Homo sapiens	101-104
20446906-1	2010	PF-02341066 is a selective c-Met/Alk tyrosine kinase inhibitor currently in clinical development as an anticancer agent.	Crizotinib	0-11	MET proto-oncogene, receptor tyrosine kinase	Rattus norvegicus	27-32
21047279-6	2010	The results obtained with crizotinib in patients with ALK gene rearrangement are a good example of the speed with which biological discoveries can be translated to clinical testing.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	54-57
20676809-1	2010	The anaplastic lymphoma kinase (ALK) inhibitor crizotinib will become an integral addition to the treatment of patients with non-small cell lung cancer (NSCLC) harboring genetic ALK translocations.	Crizotinib	47-57	ALK receptor tyrosine kinase	Homo sapiens	4-30
20676809-1	2010	The anaplastic lymphoma kinase (ALK) inhibitor crizotinib will become an integral addition to the treatment of patients with non-small cell lung cancer (NSCLC) harboring genetic ALK translocations.	Crizotinib	47-57	ALK receptor tyrosine kinase	Homo sapiens	32-35
20676809-1	2010	The anaplastic lymphoma kinase (ALK) inhibitor crizotinib will become an integral addition to the treatment of patients with non-small cell lung cancer (NSCLC) harboring genetic ALK translocations.	Crizotinib	47-57	ALK receptor tyrosine kinase	Homo sapiens	178-181
21102269-0	2010	Rapid and dramatic radiographic and clinical response to an ALK inhibitor (crizotinib, PF02341066) in an ALK translocation-positive patient with non-small cell lung cancer.	Crizotinib	75-85	ALK receptor tyrosine kinase	Homo sapiens	60-63
21102269-0	2010	Rapid and dramatic radiographic and clinical response to an ALK inhibitor (crizotinib, PF02341066) in an ALK translocation-positive patient with non-small cell lung cancer.	Crizotinib	75-85	ALK receptor tyrosine kinase	Homo sapiens	105-108
21119722-0	2010	Trial watch: success for crizotinib in ALK-driven cancer.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	39-42
20979469-2	2010	We explored the therapeutic efficacy of inhibiting ALK in such tumors in an early-phase clinical trial of crizotinib (PF-02341066), an orally available small-molecule inhibitor of the ALK tyrosine kinase.	Crizotinib	106-116	ALK receptor tyrosine kinase	Homo sapiens	184-187
20979472-0	2010	Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	14-17
20979472-3	2010	We report a sustained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) in a patient with ALK-translocated IMT, as compared with no observed activity in another patient without the ALK translocation.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	46-49
20979472-3	2010	We report a sustained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) in a patient with ALK-translocated IMT, as compared with no observed activity in another patient without the ALK translocation.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	111-114
20979472-3	2010	We report a sustained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) in a patient with ALK-translocated IMT, as compared with no observed activity in another patient without the ALK translocation.	Crizotinib	60-70	ALK receptor tyrosine kinase	Homo sapiens	111-114
20979472-3	2010	We report a sustained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) in a patient with ALK-translocated IMT, as compared with no observed activity in another patient without the ALK translocation.	Crizotinib	72-83	ALK receptor tyrosine kinase	Homo sapiens	46-49
20979472-3	2010	We report a sustained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) in a patient with ALK-translocated IMT, as compared with no observed activity in another patient without the ALK translocation.	Crizotinib	72-83	ALK receptor tyrosine kinase	Homo sapiens	111-114
20979472-3	2010	We report a sustained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) in a patient with ALK-translocated IMT, as compared with no observed activity in another patient without the ALK translocation.	Crizotinib	72-83	ALK receptor tyrosine kinase	Homo sapiens	111-114
20446906-1	2010	PF-02341066 is a selective c-Met/Alk tyrosine kinase inhibitor currently in clinical development as an anticancer agent.	Crizotinib	0-11	ALK receptor tyrosine kinase	Rattus norvegicus	33-36
18089725-0	2007	Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma.	Crizotinib	36-46	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	100-105
33588113-2	2021	METHODS: In a multicenter phase 2 trial, ALK-positive NSCLC patients who progressed on crizotinib were treated with ensartinib.	Crizotinib	87-97	ALK receptor tyrosine kinase	Homo sapiens	41-44
33776691-1	2021	We report a patient with stage IV anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (primary lung signet ring cell adenocarcinoma) who received serial crizotinib, chemotherapy, and lorlatinib over more than 4 years.	Crizotinib	172-182	ALK receptor tyrosine kinase	Homo sapiens	34-60
33761908-1	2021	BACKGROUND: Crizotinib is the approved treatment for advanced non-small cell lung cancers (NSCLCs) of anaplastic lymphoma kinase (ALK) fusion.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	102-128
33761908-1	2021	BACKGROUND: Crizotinib is the approved treatment for advanced non-small cell lung cancers (NSCLCs) of anaplastic lymphoma kinase (ALK) fusion.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	130-133
33761908-10	2021	CONCLUSION: Second-generation ALK inhibitors in crizotinib-treated patients showed a satifactory efficacy.	Crizotinib	48-58	ALK receptor tyrosine kinase	Homo sapiens	30-33
33941195-0	2021	Unclassified mesenchymal sarcoma with NTRK1-KHDRBS1 gene fusion: a case report of long-term tumor-free survival with crizotinib treatment.	Crizotinib	117-127	neurotrophic receptor tyrosine kinase 1	Homo sapiens	38-43
33941195-0	2021	Unclassified mesenchymal sarcoma with NTRK1-KHDRBS1 gene fusion: a case report of long-term tumor-free survival with crizotinib treatment.	Crizotinib	117-127	KH RNA binding domain containing, signal transduction associated 1	Homo sapiens	44-51
33794589-9	2021	Treatment with ALK inhibitors like crizotinib has brought about a paradigm shift in the management of advanced ALK-positive IMT"s with excellent clinical responses which are durable in a majority of cases.	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	15-18
33794589-9	2021	Treatment with ALK inhibitors like crizotinib has brought about a paradigm shift in the management of advanced ALK-positive IMT"s with excellent clinical responses which are durable in a majority of cases.	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	111-114
33816312-0	2021	Case Report: Neoadjuvant and Adjuvant Crizotinib Targeted Therapy in Stage IIIA-N2 ALK-Positive Non-Small-Cell Lung Cancer.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	83-86
33816312-3	2021	Herein, we show that systemic treatment with ALK inhibitor crizotinib before surgery can provide the potential to cure the initially inoperable tumor.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	45-48
33776691-1	2021	We report a patient with stage IV anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (primary lung signet ring cell adenocarcinoma) who received serial crizotinib, chemotherapy, and lorlatinib over more than 4 years.	Crizotinib	172-182	ALK receptor tyrosine kinase	Homo sapiens	62-65
33776691-10	2021	Physicians should be aware that ALK inhibitors, such as lorlatinib and crizotinib, have potentially lethal side effects.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	32-35
27370605-7	2017	A patient with metastatic ROS1-rearranged NSCLC with progression on crizotinib was treated with cabozantinib and experienced a partial response.	Crizotinib	68-78	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	26-30
34845836-1	2022	More than 60% of nonsmall cell lung cancer (NSCLC) patients show a positive response to the first ALK inhibitor, crizotinib, which has been used as the standard treatment for newly diagnosed patients with ALK rearrangement.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	98-101
34626839-0	2022	Deep RNA sequencing revealed fusion junctional heterogeneity may predict crizotinib treatment efficacy in ALK-rearranged non-small cell lung cancer.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	106-109
34626839-3	2022	METHODS: ALK-rearranged NSCLC patients who received crizotinib treatments were recruited.	Crizotinib	52-62	ALK receptor tyrosine kinase	Homo sapiens	9-12
29024938-8	2017	Crizotinib and foretinib decreased TYRO3 and AXL phosphorylation, apoptosis, G2/arrest and reduced colony formation.	Crizotinib	0-10	TYRO3 protein tyrosine kinase	Homo sapiens	35-40
29024938-8	2017	Crizotinib and foretinib decreased TYRO3 and AXL phosphorylation, apoptosis, G2/arrest and reduced colony formation.	Crizotinib	0-10	AXL receptor tyrosine kinase	Homo sapiens	45-48
29024938-13	2017	Crizotinib and foretinib showed effective antitumour activity in LMS through TYRO3 and AXL deactivation indicating that clinical trials using TYRO3 and AXL inhibitors are warranted in advanced LMS.British Journal of Cancer advance online publication 12 October 2017; doi:10.1038/bjc.2017.354 www.bjcancer.com.	Crizotinib	0-10	TYRO3 protein tyrosine kinase	Homo sapiens	77-82
29024938-13	2017	Crizotinib and foretinib showed effective antitumour activity in LMS through TYRO3 and AXL deactivation indicating that clinical trials using TYRO3 and AXL inhibitors are warranted in advanced LMS.British Journal of Cancer advance online publication 12 October 2017; doi:10.1038/bjc.2017.354 www.bjcancer.com.	Crizotinib	0-10	AXL receptor tyrosine kinase	Homo sapiens	87-90
29024938-13	2017	Crizotinib and foretinib showed effective antitumour activity in LMS through TYRO3 and AXL deactivation indicating that clinical trials using TYRO3 and AXL inhibitors are warranted in advanced LMS.British Journal of Cancer advance online publication 12 October 2017; doi:10.1038/bjc.2017.354 www.bjcancer.com.	Crizotinib	0-10	TYRO3 protein tyrosine kinase	Homo sapiens	142-147
29024938-13	2017	Crizotinib and foretinib showed effective antitumour activity in LMS through TYRO3 and AXL deactivation indicating that clinical trials using TYRO3 and AXL inhibitors are warranted in advanced LMS.British Journal of Cancer advance online publication 12 October 2017; doi:10.1038/bjc.2017.354 www.bjcancer.com.	Crizotinib	0-10	AXL receptor tyrosine kinase	Homo sapiens	152-155
34845836-1	2022	More than 60% of nonsmall cell lung cancer (NSCLC) patients show a positive response to the first ALK inhibitor, crizotinib, which has been used as the standard treatment for newly diagnosed patients with ALK rearrangement.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	205-208
34845836-2	2022	However, most patients inevitably develop crizotinib resistance due to acquired secondary mutations in the ALK kinase domain, such as the gatekeeper mutation L1196M and the most refractory mutation, G1202R.	Crizotinib	42-52	anaplastic lymphoma kinase	Mus musculus	107-110
34845836-3	2022	Here, we develop XMU-MP-5 as a new-generation ALK inhibitor to overcome crizotinib resistance mutations, including L1196M and G1202R.	Crizotinib	72-82	anaplastic lymphoma kinase	Mus musculus	46-49
34913728-6	2022	METHODS: This retrospective observational study used US commercial claims for patients aged at least 18 years with lung cancer receiving ALK inhibitors (alectinib, brigatinib, ceritinib, crizotinib) between July 1, 2015, and December 31, 2018.	Crizotinib	187-197	ALK receptor tyrosine kinase	Homo sapiens	137-140
34802880-0	2022	Acquired MET-DSTN Fusion Mediated Resistance to EGFR-TKIs in Lung Adenocarcinoma and Responded to Crizotinib Plus Gefitinib: A Case Report.	Crizotinib	98-108	SAFB like transcription modulator	Homo sapiens	9-12
34802880-0	2022	Acquired MET-DSTN Fusion Mediated Resistance to EGFR-TKIs in Lung Adenocarcinoma and Responded to Crizotinib Plus Gefitinib: A Case Report.	Crizotinib	98-108	destrin, actin depolymerizing factor	Homo sapiens	13-17
34964940-0	2022	Real-World Outcomes Among Crizotinib-Treated Patients with ROS1-Positive Advanced Non-Small-Cell Lung Cancer: A Community Oncology-Based Observational Study.	Crizotinib	26-36	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	59-63
34964940-1	2022	BACKGROUND: Crizotinib was the first oral targeted therapy approved by the US Food and Drug Administration (FDA), on 11 March 2016, for c-ros oncogene 1 (ROS1)-positive advanced non-small-cell lung cancer (NSCLC).	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	136-152
34964940-1	2022	BACKGROUND: Crizotinib was the first oral targeted therapy approved by the US Food and Drug Administration (FDA), on 11 March 2016, for c-ros oncogene 1 (ROS1)-positive advanced non-small-cell lung cancer (NSCLC).	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	154-158
34964940-3	2022	OBJECTIVE: This study aimed to assess real-world clinical outcomes among patients with ROS1-positive advanced NSCLC treated with crizotinib in the US community oncology setting.	Crizotinib	129-139	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	87-91
34964940-8	2022	RESULTS: The study cohort included 38 ROS1-positive patients treated with crizotinib.	Crizotinib	74-84	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	38-42
34670356-3	2021	The first and second generation ALK inhibitors (ALKi), such as crizotinib, ceritinib, alectinib and ensartinib have been approved in China.	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	32-35
34913728-15	2022	In the ALK inhibitor-naive cohort, median time to treatment discontinuation with alectinib and crizotinib was 27.1 and 8.8 months, respectively; patients receiving alectinib were 46% less likely to discontinue than patients receiving crizotinib (adjusted hazard ratio (aHR) (95% CI): 0.54 (0.44-0.65); P < 0.0001).	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	7-10
34551905-1	2021	PURPOSE: The clinical phase II trial EORTC 90101 "CREATE" showed high anti-tumor activity of crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK)/ROS1, in patients with advanced inflammatory myofibroblastic tumor (IMFT).	Crizotinib	93-103	ALK receptor tyrosine kinase	Homo sapiens	121-147
34551905-1	2021	PURPOSE: The clinical phase II trial EORTC 90101 "CREATE" showed high anti-tumor activity of crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK)/ROS1, in patients with advanced inflammatory myofibroblastic tumor (IMFT).	Crizotinib	93-103	ALK receptor tyrosine kinase	Homo sapiens	149-152
34551905-1	2021	PURPOSE: The clinical phase II trial EORTC 90101 "CREATE" showed high anti-tumor activity of crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK)/ROS1, in patients with advanced inflammatory myofibroblastic tumor (IMFT).	Crizotinib	93-103	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	154-158
34551905-7	2021	One ALK-negative patient responding to crizotinib was found to have an ETV6-NTRK fusion in the tumor specimen.	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	4-7
34551905-7	2021	One ALK-negative patient responding to crizotinib was found to have an ETV6-NTRK fusion in the tumor specimen.	Crizotinib	39-49	ETS variant transcription factor 6	Homo sapiens	71-75
34551905-9	2021	Loss of chromosome 19 (25% of cases) and PIK3CA mutations (9% of cases) were associated with shorter progression-free survival in patients receiving crizotinib.	Crizotinib	149-159	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	41-47
34957997-0	2021	Curcumin increases crizotinib sensitivity through the inactivation of autophagy via epigenetic modulation of the miR-142-5p/Ulk1 axis in non-small cell lung cancer.	Crizotinib	19-29	unc-51 like autophagy activating kinase 1	Homo sapiens	124-128
34915469-0	2022	Crizotinib versus Alectinib for the Treatment of ALK-Positive Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	49-52
34915469-1	2022	BACKGROUND: Crizotinib and alectinib are the two most commonly used anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	68-94
34915469-1	2022	BACKGROUND: Crizotinib and alectinib are the two most commonly used anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	96-99
34915469-1	2022	BACKGROUND: Crizotinib and alectinib are the two most commonly used anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	116-119
34915469-9	2022	The crizotinib group reported higher rates of constipation, nausea, diarrhea, vomiting, peripheral edema, dysgeusia, visual impairment and levels of alanine aminotransferase and aspartate aminotransferase as well as greater decreases in appetite and neutrophil count.	Crizotinib	4-14	glutamic--pyruvic transaminase	Homo sapiens	149-173
34907086-4	2022	In addition, lorlatinib and repotrectinib are actively being explored in the setting of treatment naive or crizotinib-resistant ROS1 fusion driven NSCLC.	Crizotinib	107-117	Ros1 proto-oncogene	Mus musculus	128-132
34957368-12	2021	Moreover, RET-CCDC6 fusion and EGFR mutation were detected following crizotinib treatment in two patients, suggesting novel mechanisms of resistance.	Crizotinib	69-79	ret proto-oncogene	Homo sapiens	10-13
34957368-12	2021	Moreover, RET-CCDC6 fusion and EGFR mutation were detected following crizotinib treatment in two patients, suggesting novel mechanisms of resistance.	Crizotinib	69-79	coiled-coil domain containing 6	Homo sapiens	14-19
34957368-12	2021	Moreover, RET-CCDC6 fusion and EGFR mutation were detected following crizotinib treatment in two patients, suggesting novel mechanisms of resistance.	Crizotinib	69-79	epidermal growth factor receptor	Homo sapiens	31-35
34957997-11	2021	Collectively, our findings demonstrate that curcumin sensitizes NSCLC cells to crizotinib by inactivating autophagy through the regulation of miR-142-5p and its target Ulk1.	Crizotinib	79-89	unc-51 like autophagy activating kinase 1	Homo sapiens	168-172
34885165-2	2021	The EORTC 90101 phase II trial evaluated the MET inhibitor crizotinib in CCSA but resulted in only sporadic responses.	Crizotinib	59-69	SAFB like transcription modulator	Homo sapiens	45-48
34875133-14	2022	ROS1 fusions (CEP85L-ROS1 and GOPC-ROS1), identified in 8% of patient cfDNA, might be targeted by crizotinib, entrectinib or larotrectinib.	Crizotinib	98-108	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	0-4
34875133-14	2022	ROS1 fusions (CEP85L-ROS1 and GOPC-ROS1), identified in 8% of patient cfDNA, might be targeted by crizotinib, entrectinib or larotrectinib.	Crizotinib	98-108	centrosomal protein 85 like	Homo sapiens	14-20
34875133-14	2022	ROS1 fusions (CEP85L-ROS1 and GOPC-ROS1), identified in 8% of patient cfDNA, might be targeted by crizotinib, entrectinib or larotrectinib.	Crizotinib	98-108	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	21-25
34875133-14	2022	ROS1 fusions (CEP85L-ROS1 and GOPC-ROS1), identified in 8% of patient cfDNA, might be targeted by crizotinib, entrectinib or larotrectinib.	Crizotinib	98-108	golgi associated PDZ and coiled-coil motif containing	Homo sapiens	30-39
34428672-9	2021	The analysis of sEVs from a patient prior and post ALK-TKI crizotinib treatment reveals significant increases in the expressions of some markers (EGFR and PD-L1).	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	51-54
34428672-9	2021	The analysis of sEVs from a patient prior and post ALK-TKI crizotinib treatment reveals significant increases in the expressions of some markers (EGFR and PD-L1).	Crizotinib	59-69	epidermal growth factor receptor	Homo sapiens	146-150
34428672-9	2021	The analysis of sEVs from a patient prior and post ALK-TKI crizotinib treatment reveals significant increases in the expressions of some markers (EGFR and PD-L1).	Crizotinib	59-69	CD274 molecule	Homo sapiens	155-160
34550531-12	2021	CONCLUSION: Our screen revealed promising combinations with EGFRis, such as the ALK/MET-inhibitor crizotinib, the HDAC-inhibitor panobinostat or the topoisomerase-II-inhibitor doxorubicin, which are part of standard chemotherapy regimens for various bone and soft-tissue sarcomas.	Crizotinib	98-108	ALK receptor tyrosine kinase	Homo sapiens	80-83
34550531-12	2021	CONCLUSION: Our screen revealed promising combinations with EGFRis, such as the ALK/MET-inhibitor crizotinib, the HDAC-inhibitor panobinostat or the topoisomerase-II-inhibitor doxorubicin, which are part of standard chemotherapy regimens for various bone and soft-tissue sarcomas.	Crizotinib	98-108	SAFB like transcription modulator	Homo sapiens	84-87
34580063-9	2021	Senescent astrocytes secreted HGF to activate Met in glioma cells and promote their migration and invasion in vitro, which could be blocked by HGF-neutralizing antibodies or the Met inhibitor crizotinib.	Crizotinib	192-202	hepatocyte growth factor	Mus musculus	30-33
34885165-16	2021	Conclusions: The infrequent activation of MET may explain the lack of response to crizotinib observed in the majority of cases in the clinical trial.	Crizotinib	82-92	SAFB like transcription modulator	Homo sapiens	42-45
34373943-0	2021	Crizotinib: aseptic abscesses in multiple organs during treatment of EML4-ALK-positive NSCLC.	Crizotinib	0-10	EMAP like 4	Homo sapiens	69-73
34373943-0	2021	Crizotinib: aseptic abscesses in multiple organs during treatment of EML4-ALK-positive NSCLC.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	74-77
34373943-1	2021	PURPOSE: We report a novel side effect of Crizotinib, an oral ALK inhibitor used in the treatment of non-small cell lung cancer (NSCLC) with activating rearrangement of EML4-ALK.	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	62-65
34373943-1	2021	PURPOSE: We report a novel side effect of Crizotinib, an oral ALK inhibitor used in the treatment of non-small cell lung cancer (NSCLC) with activating rearrangement of EML4-ALK.	Crizotinib	42-52	EMAP like 4	Homo sapiens	169-173
34373943-1	2021	PURPOSE: We report a novel side effect of Crizotinib, an oral ALK inhibitor used in the treatment of non-small cell lung cancer (NSCLC) with activating rearrangement of EML4-ALK.	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	174-177
34516041-0	2021	BRAF V600E Mediates Crizotinib Resistance and Responds to Dabrafenib and Trametinib in a ROS1-rearranged NSCLC: a Case Report.	Crizotinib	20-30	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	0-4
34761497-5	2021	Combining the PARP inhibitor olaparib with the MET inhibitor crizotinib synergistically inhibited CRPC cell growth both in vivo and in vitro.	Crizotinib	61-71	poly(ADP-ribose) polymerase 1	Homo sapiens	14-18
34761497-5	2021	Combining the PARP inhibitor olaparib with the MET inhibitor crizotinib synergistically inhibited CRPC cell growth both in vivo and in vitro.	Crizotinib	61-71	SAFB like transcription modulator	Homo sapiens	47-50
34761497-6	2021	Further analysis of the underlying molecular mechanism underlying the MET suppression-induced drug sensitivity revealed that olaparib and crizotinib could together downregulate the ATM/ATR signaling pathway, inducing apoptosis by inhibiting the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, enhancing the olaparib-induced antitumour effect in DU145 and PC3 cells.	Crizotinib	138-148	SAFB like transcription modulator	Homo sapiens	70-73
34761497-6	2021	Further analysis of the underlying molecular mechanism underlying the MET suppression-induced drug sensitivity revealed that olaparib and crizotinib could together downregulate the ATM/ATR signaling pathway, inducing apoptosis by inhibiting the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, enhancing the olaparib-induced antitumour effect in DU145 and PC3 cells.	Crizotinib	138-148	ATM serine/threonine kinase	Homo sapiens	181-184
34761497-6	2021	Further analysis of the underlying molecular mechanism underlying the MET suppression-induced drug sensitivity revealed that olaparib and crizotinib could together downregulate the ATM/ATR signaling pathway, inducing apoptosis by inhibiting the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, enhancing the olaparib-induced antitumour effect in DU145 and PC3 cells.	Crizotinib	138-148	ATR serine/threonine kinase	Homo sapiens	185-188
34761497-6	2021	Further analysis of the underlying molecular mechanism underlying the MET suppression-induced drug sensitivity revealed that olaparib and crizotinib could together downregulate the ATM/ATR signaling pathway, inducing apoptosis by inhibiting the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, enhancing the olaparib-induced antitumour effect in DU145 and PC3 cells.	Crizotinib	138-148	protein tyrosine kinase 2 beta	Homo sapiens	271-287
34761497-6	2021	Further analysis of the underlying molecular mechanism underlying the MET suppression-induced drug sensitivity revealed that olaparib and crizotinib could together downregulate the ATM/ATR signaling pathway, inducing apoptosis by inhibiting the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, enhancing the olaparib-induced antitumour effect in DU145 and PC3 cells.	Crizotinib	138-148	AKT serine/threonine kinase 1	Homo sapiens	294-297
34117602-9	2021	CONCLUSION: The study highlighted and confirmed that treatment with crizotinib led to clinical improvement in PFS among patients with advanced NSCLC with ALK fusion, as previously reported.	Crizotinib	68-78	ALK receptor tyrosine kinase	Homo sapiens	154-157
34516041-1	2021	Crizotinib, a multi-targeted MET/ALK/ROS1 tyrosine kinase inhibitor, has been approved for the treatment of ROS1 fusion-positive NSCLCs.	Crizotinib	0-10	SAFB like transcription modulator	Homo sapiens	29-32
34516041-1	2021	Crizotinib, a multi-targeted MET/ALK/ROS1 tyrosine kinase inhibitor, has been approved for the treatment of ROS1 fusion-positive NSCLCs.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	33-36
34516041-1	2021	Crizotinib, a multi-targeted MET/ALK/ROS1 tyrosine kinase inhibitor, has been approved for the treatment of ROS1 fusion-positive NSCLCs.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	37-41
34516041-1	2021	Crizotinib, a multi-targeted MET/ALK/ROS1 tyrosine kinase inhibitor, has been approved for the treatment of ROS1 fusion-positive NSCLCs.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	108-112
34516041-3	2021	Patients with ROS1-rearranged NSCLC who develop crizotinib resistance, especially those acquiring "off-target" resistance mutations, still lack effective therapeutic options for post-crizotinib treatment.	Crizotinib	48-58	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	14-18
34516041-4	2021	Herein, we reported a stage IVb lung adenocarcinoma patient harboring ROS1 fusion, who acquired a BRAF V600E and lost the ROS1 fusion after progression on crizotinib.	Crizotinib	155-165	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	70-74
34516041-4	2021	Herein, we reported a stage IVb lung adenocarcinoma patient harboring ROS1 fusion, who acquired a BRAF V600E and lost the ROS1 fusion after progression on crizotinib.	Crizotinib	155-165	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	122-126
34516041-7	2021	Our study revealed that BRAF V600E can confer the crizotinib resistance in ROS1 fusion-positive NSCLC and presented the first case showing that the treatment with dabrafenib and trametinib can serve as an effective option for later-line treatment for this molecular-defined subgroup.	Crizotinib	50-60	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	24-28
34516041-7	2021	Our study revealed that BRAF V600E can confer the crizotinib resistance in ROS1 fusion-positive NSCLC and presented the first case showing that the treatment with dabrafenib and trametinib can serve as an effective option for later-line treatment for this molecular-defined subgroup.	Crizotinib	50-60	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	75-79
34516041-8	2021	KEY POINTS: Patients with ROS1-rearranged NSCLC who acquire "off-target" resistance mutations to crizotinib, still lack effective therapeutic options for post-crizotinib treatment.	Crizotinib	97-107	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	26-30
34516041-9	2021	This report describes a case of ROS1-rearranged NSCLC who acquired a BRAF V600E and lost the ROS1 fusion after crizotinib failure.	Crizotinib	111-121	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	32-36
34516041-9	2021	This report describes a case of ROS1-rearranged NSCLC who acquired a BRAF V600E and lost the ROS1 fusion after crizotinib failure.	Crizotinib	111-121	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	93-97
34423676-1	2021	Crizotinib is highly efficacious and more tolerable than chemotherapy for ALK+ non-small-cell lung cancer (NSCLC), but its progression-free survival benefit and intracranial efficacy have limitations.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	74-77
34729938-0	2021	Hexokinases II-mediated glycolysis governs susceptibility to crizotinib in ALK-positive non-small cell lung cancer.	Crizotinib	61-71	ALK receptor tyrosine kinase	Homo sapiens	75-78
34729938-1	2021	BACKGROUND: Activation of ALK leads to a high level of aerobic glycolysis related to crizotinib insensitivity in anaplastic lymphoma kinase-positive non-small cell lung cancer (ALK+ NSCLC).	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	26-29
34729938-2	2021	The strategy and mechanism of glycolysis inhibition in sensitizing ALK+ NSCLC cells to crizotinib requires further investigation.	Crizotinib	87-97	ALK receptor tyrosine kinase	Homo sapiens	67-70
34729938-6	2021	Long-term exposure to crizotinib could decrease the sensitivity of ALK+ NSCLC cells to crizotinib via increasing the levels of glycolysis related to hexokinases II (HK2).	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	67-70
34729938-6	2021	Long-term exposure to crizotinib could decrease the sensitivity of ALK+ NSCLC cells to crizotinib via increasing the levels of glycolysis related to hexokinases II (HK2).	Crizotinib	22-32	hexokinase 2	Homo sapiens	165-168
34729938-6	2021	Long-term exposure to crizotinib could decrease the sensitivity of ALK+ NSCLC cells to crizotinib via increasing the levels of glycolysis related to hexokinases II (HK2).	Crizotinib	87-97	ALK receptor tyrosine kinase	Homo sapiens	67-70
34729938-6	2021	Long-term exposure to crizotinib could decrease the sensitivity of ALK+ NSCLC cells to crizotinib via increasing the levels of glycolysis related to hexokinases II (HK2).	Crizotinib	87-97	hexokinase 2	Homo sapiens	165-168
34729938-7	2021	Crizotinib in combination with glycolysis inhibitor 2-deoxy-D-glucose (2DG) synergistically inhibited proliferation, glycolysis, colony formation and invasion ability of ALK+ NSCLC cells.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	170-173
34729938-8	2021	2DG sensitization crizotinib might be associated with the inhibition of HK2-mediated glycolysis and P-ALK/AKT/mTOR signaling pathway in H3122 and H2228 cells.	Crizotinib	18-28	hexokinase 2	Homo sapiens	72-75
34729938-8	2021	2DG sensitization crizotinib might be associated with the inhibition of HK2-mediated glycolysis and P-ALK/AKT/mTOR signaling pathway in H3122 and H2228 cells.	Crizotinib	18-28	ALK receptor tyrosine kinase	Homo sapiens	102-105
34729938-8	2021	2DG sensitization crizotinib might be associated with the inhibition of HK2-mediated glycolysis and P-ALK/AKT/mTOR signaling pathway in H3122 and H2228 cells.	Crizotinib	18-28	AKT serine/threonine kinase 1	Homo sapiens	106-109
34729938-8	2021	2DG sensitization crizotinib might be associated with the inhibition of HK2-mediated glycolysis and P-ALK/AKT/mTOR signaling pathway in H3122 and H2228 cells.	Crizotinib	18-28	mechanistic target of rapamycin kinase	Homo sapiens	110-114
34729938-9	2021	CONCLUSIONS: These results indicate that HK2-mediated glycolysis plays a crucial role in the increased tolerance of ALK+ NSCLC cells to crizotinib.	Crizotinib	136-146	hexokinase 2	Homo sapiens	41-44
34729938-9	2021	CONCLUSIONS: These results indicate that HK2-mediated glycolysis plays a crucial role in the increased tolerance of ALK+ NSCLC cells to crizotinib.	Crizotinib	136-146	ALK receptor tyrosine kinase	Homo sapiens	116-119
34729938-10	2021	2DG may sensitize ALK+ NSCLC to crizotinib via suppression of HK2-mediated glycolysis and the AKT/mTOR signaling pathway.	Crizotinib	32-42	ALK receptor tyrosine kinase	Homo sapiens	18-21
34729938-10	2021	2DG may sensitize ALK+ NSCLC to crizotinib via suppression of HK2-mediated glycolysis and the AKT/mTOR signaling pathway.	Crizotinib	32-42	hexokinase 2	Homo sapiens	62-65
34729938-10	2021	2DG may sensitize ALK+ NSCLC to crizotinib via suppression of HK2-mediated glycolysis and the AKT/mTOR signaling pathway.	Crizotinib	32-42	AKT serine/threonine kinase 1	Homo sapiens	94-97
34729938-10	2021	2DG may sensitize ALK+ NSCLC to crizotinib via suppression of HK2-mediated glycolysis and the AKT/mTOR signaling pathway.	Crizotinib	32-42	mechanistic target of rapamycin kinase	Homo sapiens	98-102
34956530-1	2021	BACKGROUND: To investigate the clinical efficacy and safety of crizotinib and alectinib in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) treatment and the predictive value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125) for treatment efficacy.	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	91-117
34956530-1	2021	BACKGROUND: To investigate the clinical efficacy and safety of crizotinib and alectinib in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) treatment and the predictive value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125) for treatment efficacy.	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	119-122
34832908-0	2021	Repurposing of the ALK Inhibitor Crizotinib for Acute Leukemia and Multiple Myeloma Cells.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	19-22
34832908-1	2021	Crizotinib was a first generation of ALK tyrosine kinase inhibitor approved for the treatment of ALK-positive non-small-cell lung carcinoma (NSCLC) patients.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	97-100
34832908-7	2021	P-glycoprotein-overexpressing CEM/ADR5000 leukemia cells were cross-resistant to crizotinib.	Crizotinib	81-91	ATP binding cassette subfamily B member 1	Homo sapiens	0-14
34832908-11	2021	The altered gene expression profiles after crizotinib treatment predicted several networks, where TOP2A and genes related to cell cycle were downregulated.	Crizotinib	43-53	DNA topoisomerase II alpha	Homo sapiens	98-103
34482598-3	2021	Crizotinib is a small molecule inhibitor that targets mesenchymal epithelial transition factor (c-MET) and has been successfully studied for its anti-cancer effects in non-small cell lung cancer, pancreatic, gastric, renal, prostate, and breast carcinomas.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	96-101
34418561-6	2021	Among ALK/ROS1 inhibitors, crizotinib had highest odds of conduction disease (ROR 1.75, 99% CI: 1.30-2.36) and QT prolongation (ROR 1.91, 99% CI: 1.22-3.00).	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	6-9
34418561-6	2021	Among ALK/ROS1 inhibitors, crizotinib had highest odds of conduction disease (ROR 1.75, 99% CI: 1.30-2.36) and QT prolongation (ROR 1.91, 99% CI: 1.22-3.00).	Crizotinib	27-37	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	10-14
34418561-6	2021	Among ALK/ROS1 inhibitors, crizotinib had highest odds of conduction disease (ROR 1.75, 99% CI: 1.30-2.36) and QT prolongation (ROR 1.91, 99% CI: 1.22-3.00).	Crizotinib	27-37	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	78-83
34418561-6	2021	Among ALK/ROS1 inhibitors, crizotinib had highest odds of conduction disease (ROR 1.75, 99% CI: 1.30-2.36) and QT prolongation (ROR 1.91, 99% CI: 1.22-3.00).	Crizotinib	27-37	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	128-133
34853656-7	2021	CCL20-dependent proliferation, however, is blocked by the multi-tyrosine kinase inhibitor crizotinib.	Crizotinib	90-100	C-C motif chemokine ligand 20	Homo sapiens	0-5
34582848-0	2021	Stereospecific inhibition of AMPK by (R)-crizotinib induced changes to the morphology and properties of cancer and cancer stem cell-like cells.	Crizotinib	37-51	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	29-33
34582848-1	2021	Crizotinib is used in the clinic for treating patients with ALK- or ROS1-positive non-small-cell lung carcinoma.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	68-72
34582848-7	2021	Along with the morphological changes induced by (R)-crizotinib, the expression levels of CD44 (NCI-H23 and HCT-15), ALDH1 (NCI-H460), nanog (PC-3), and Oct-4A (CSC-like cells), which appear to be specific marker proteins, were greatly changed, suggesting that changes in cellular properties accompanied the morphological changes in the cells.	Crizotinib	48-62	CD44 molecule (Indian blood group)	Homo sapiens	89-93
34582848-7	2021	Along with the morphological changes induced by (R)-crizotinib, the expression levels of CD44 (NCI-H23 and HCT-15), ALDH1 (NCI-H460), nanog (PC-3), and Oct-4A (CSC-like cells), which appear to be specific marker proteins, were greatly changed, suggesting that changes in cellular properties accompanied the morphological changes in the cells.	Crizotinib	48-62	aldehyde dehydrogenase 1 family member A1	Homo sapiens	116-121
34582848-8	2021	The expression levels of Snail, Slug, and E-cadherin were also greatly altered by (R)-crizotinib.	Crizotinib	82-96	snail family transcriptional repressor 1	Homo sapiens	25-30
34582848-8	2021	The expression levels of Snail, Slug, and E-cadherin were also greatly altered by (R)-crizotinib.	Crizotinib	82-96	snail family transcriptional repressor 2	Homo sapiens	32-36
34582848-8	2021	The expression levels of Snail, Slug, and E-cadherin were also greatly altered by (R)-crizotinib.	Crizotinib	82-96	cadherin 1	Homo sapiens	42-52
34582848-9	2021	Among several signal transduction molecules examined, AMPK phosphorylation appeared to be selectively inhibited by (R)-crizotinib.	Crizotinib	115-129	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	54-58
34582848-10	2021	BML-275 (an AMPK inhibitor) and AMPKalpha2 siRNA efficiently induced morphological changes to all types of cells examined, suggesting that (R)-crizotinib might cause losses of characteristics of cancer or CSCs via inhibition of AMPK.	Crizotinib	139-153	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	12-16
34582848-10	2021	BML-275 (an AMPK inhibitor) and AMPKalpha2 siRNA efficiently induced morphological changes to all types of cells examined, suggesting that (R)-crizotinib might cause losses of characteristics of cancer or CSCs via inhibition of AMPK.	Crizotinib	139-153	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	32-42
34582848-10	2021	BML-275 (an AMPK inhibitor) and AMPKalpha2 siRNA efficiently induced morphological changes to all types of cells examined, suggesting that (R)-crizotinib might cause losses of characteristics of cancer or CSCs via inhibition of AMPK.	Crizotinib	139-153	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	228-232
34754197-5	2021	The patient underwent a multidisciplinary treatment scheme that consisted of radiotherapy, ALK inhibitor crizotinib, and surgery, with blood-based genomic profiling for monitoring disease progression.	Crizotinib	105-115	ALK receptor tyrosine kinase	Homo sapiens	91-94
34754197-6	2021	Notably, salvage thoracic surgery was performed after progression on the crizotinib therapy and acquired ALK F1174C mutation was identified, which has been shown to be resistant to crizotinib and possibly sensitive to ceritinib.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	105-108
34754197-6	2021	Notably, salvage thoracic surgery was performed after progression on the crizotinib therapy and acquired ALK F1174C mutation was identified, which has been shown to be resistant to crizotinib and possibly sensitive to ceritinib.	Crizotinib	181-191	ALK receptor tyrosine kinase	Homo sapiens	105-108
34145176-5	2021	Ultimately, next-generation sequencing of the tumor revealed a TFG-ROS-1 translocation, allowing for an off-label targeted therapy with crizotinib.	Crizotinib	136-146	trafficking from ER to golgi regulator	Homo sapiens	63-66
34473194-2	2021	Objective: To compare ensartinib with crizotinib among patients with advanced ALK-positive NSCLC who had not received prior treatment with an ALK inhibitor.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	78-81
34375729-0	2021	Design, synthesis and application of near-infrared fluorescence probe IR-780-Crizotinib in detection of ALK positive tumors.	Crizotinib	77-87	anaplastic lymphoma kinase	Mus musculus	104-107
34994615-0	2021	Overcoming Acquired Resistance Mutation MET D1228N to Crizotinib With Cabozantinib in NSCLC With MET Exon 14 Skipping Mutation.	Crizotinib	54-64	SAFB like transcription modulator	Homo sapiens	40-43
34375729-3	2021	In this study, based on the Crizotinib has a good targeted inhibitory effect on ALK positive tumor cells, the near-infrared targeted fluorescent dye IR-780 was covalently bound with the drug molecule Crizotinib, thus the near-infrared fluorescent probe IR-780-Crizotinib targeting ALK positive tumor cells was synthesized.	Crizotinib	28-38	anaplastic lymphoma kinase	Mus musculus	80-83
34375729-3	2021	In this study, based on the Crizotinib has a good targeted inhibitory effect on ALK positive tumor cells, the near-infrared targeted fluorescent dye IR-780 was covalently bound with the drug molecule Crizotinib, thus the near-infrared fluorescent probe IR-780-Crizotinib targeting ALK positive tumor cells was synthesized.	Crizotinib	28-38	anaplastic lymphoma kinase	Mus musculus	281-284
34375729-3	2021	In this study, based on the Crizotinib has a good targeted inhibitory effect on ALK positive tumor cells, the near-infrared targeted fluorescent dye IR-780 was covalently bound with the drug molecule Crizotinib, thus the near-infrared fluorescent probe IR-780-Crizotinib targeting ALK positive tumor cells was synthesized.	Crizotinib	200-210	anaplastic lymphoma kinase	Mus musculus	80-83
34375729-3	2021	In this study, based on the Crizotinib has a good targeted inhibitory effect on ALK positive tumor cells, the near-infrared targeted fluorescent dye IR-780 was covalently bound with the drug molecule Crizotinib, thus the near-infrared fluorescent probe IR-780-Crizotinib targeting ALK positive tumor cells was synthesized.	Crizotinib	200-210	anaplastic lymphoma kinase	Mus musculus	281-284
34375729-3	2021	In this study, based on the Crizotinib has a good targeted inhibitory effect on ALK positive tumor cells, the near-infrared targeted fluorescent dye IR-780 was covalently bound with the drug molecule Crizotinib, thus the near-infrared fluorescent probe IR-780-Crizotinib targeting ALK positive tumor cells was synthesized.	Crizotinib	260-270	anaplastic lymphoma kinase	Mus musculus	80-83
34375729-3	2021	In this study, based on the Crizotinib has a good targeted inhibitory effect on ALK positive tumor cells, the near-infrared targeted fluorescent dye IR-780 was covalently bound with the drug molecule Crizotinib, thus the near-infrared fluorescent probe IR-780-Crizotinib targeting ALK positive tumor cells was synthesized.	Crizotinib	260-270	anaplastic lymphoma kinase	Mus musculus	281-284
34623764-0	2021	Small cell transformation in crizotinib-resistant ROS1-rearranged non-small cell lung cancer with retention of ROS1 fusion: A case report.	Crizotinib	29-39	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	50-54
34623764-5	2021	Here, we present the case of a 63-year-old man with ROS1-rearranged advanced NSCLC who had disease progression with small cell transformation of the mediastinal lymph node after 8 months of treatment with crizotinib.	Crizotinib	205-215	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	52-56
34778041-0	2021	A Novel c-Mesenchymal-Epithelial Transition Factor Intergenic Fusion Response to Crizotinib in a Chinese Patient With Lung Adenocarcinoma: A Case Report.	Crizotinib	81-91	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	8-50
34715804-0	2021	Cost-effectiveness analysis of first-line treatment with crizotinib in ROS1-rearranged advanced non-small cell lung cancer (NSCLC) in Canada.	Crizotinib	57-67	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	71-75
34715804-2	2021	The objective of this study was to assess the cost-effectiveness of crizotinib compared to standard platinum-doublet chemotherapy for first-line treatment of ROS1+ advanced NSCLC.	Crizotinib	68-78	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	158-162
34715804-10	2021	A scenario analysis assuming efficacy equivalent to the ALK+ NSCLC population showed a slightly more favorable cost-effectiveness profile for crizotinib.	Crizotinib	142-152	ALK receptor tyrosine kinase	Homo sapiens	56-59
34715804-11	2021	CONCLUSIONS: Available data appear to support superior activity of crizotinib compared to chemotherapy in ROS1+ advanced NSCLC.	Crizotinib	67-77	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	106-110
34778041-8	2021	Conclusion: This was the first case of a patient with LADC with MET intergenic fusion who significantly benefited from crizotinib.	Crizotinib	119-129	SAFB like transcription modulator	Homo sapiens	64-67
34778041-9	2021	Even after crizotinib was discontinued for 5 months, the patient continued exhibiting PR, suggesting that MET intergenic fusion may have carcinogenic activity in LADC and was sensitive to crizotinib.	Crizotinib	11-21	SAFB like transcription modulator	Homo sapiens	106-109
34778041-9	2021	Even after crizotinib was discontinued for 5 months, the patient continued exhibiting PR, suggesting that MET intergenic fusion may have carcinogenic activity in LADC and was sensitive to crizotinib.	Crizotinib	188-198	SAFB like transcription modulator	Homo sapiens	106-109
34686712-0	2021	Crizotinib efficacy in advanced non-squamous NSCLC patients with ALK or ROS1 rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	65-68
34686712-0	2021	Crizotinib efficacy in advanced non-squamous NSCLC patients with ALK or ROS1 rearrangement.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	72-76
34686712-5	2021	In patients with ALK and ROS1 genes alteration, the median overall survival was 34 months in crizotinib treated patients and 6 months in patients who received chemotherapy (HR = 0.266, p = 0.0056).	Crizotinib	93-103	ALK receptor tyrosine kinase	Homo sapiens	17-20
34686712-5	2021	In patients with ALK and ROS1 genes alteration, the median overall survival was 34 months in crizotinib treated patients and 6 months in patients who received chemotherapy (HR = 0.266, p = 0.0056).	Crizotinib	93-103	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	25-29
34657149-8	2022	Downstream signaling analysis showed that deletion of PTPN1 or PTPN2 induces resistance to crizotinib by hyperactivating SHP2, the MAPK and JAK/STAT pathways.	Crizotinib	91-101	protein tyrosine phosphatase non-receptor type 1	Homo sapiens	54-59
34712511-3	2021	However, we found that low-dose of ALK inhibitors, crizotinib and ceritinib, may stimulate ICD in anaplastic large cell lymphoma, in which ALK is activated due to a chromosomal translocation, suggesting on target ICD-promoting effects.	Crizotinib	51-61	ALK receptor tyrosine kinase	Homo sapiens	35-38
34687488-8	2022	The most common coexisting gene was TP53 among 11 patients and 2 of 4 patients after crizotinib failure harbored acquired ALK mutations (e.g., L1152V/Q1146K and L1196M).	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	122-125
34687488-10	2022	Although HIP1-ALK-rearranged NSCLC appears to initially respond well to ALK-TKIs, crizotinib resistance may be correlated with the AKAP9-BRAF fusion, ALK compound mutations (L1152V/Q1146K), and the ALK L1196M mutation.	Crizotinib	82-92	ALK receptor tyrosine kinase	Homo sapiens	14-17
34687488-10	2022	Although HIP1-ALK-rearranged NSCLC appears to initially respond well to ALK-TKIs, crizotinib resistance may be correlated with the AKAP9-BRAF fusion, ALK compound mutations (L1152V/Q1146K), and the ALK L1196M mutation.	Crizotinib	82-92	A-kinase anchoring protein 9	Homo sapiens	131-136
34687488-10	2022	Although HIP1-ALK-rearranged NSCLC appears to initially respond well to ALK-TKIs, crizotinib resistance may be correlated with the AKAP9-BRAF fusion, ALK compound mutations (L1152V/Q1146K), and the ALK L1196M mutation.	Crizotinib	82-92	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	137-141
34687488-10	2022	Although HIP1-ALK-rearranged NSCLC appears to initially respond well to ALK-TKIs, crizotinib resistance may be correlated with the AKAP9-BRAF fusion, ALK compound mutations (L1152V/Q1146K), and the ALK L1196M mutation.	Crizotinib	82-92	ALK receptor tyrosine kinase	Homo sapiens	150-153
34687488-10	2022	Although HIP1-ALK-rearranged NSCLC appears to initially respond well to ALK-TKIs, crizotinib resistance may be correlated with the AKAP9-BRAF fusion, ALK compound mutations (L1152V/Q1146K), and the ALK L1196M mutation.	Crizotinib	82-92	ALK receptor tyrosine kinase	Homo sapiens	198-201
34657149-8	2022	Downstream signaling analysis showed that deletion of PTPN1 or PTPN2 induces resistance to crizotinib by hyperactivating SHP2, the MAPK and JAK/STAT pathways.	Crizotinib	91-101	protein tyrosine phosphatase non-receptor type 2	Homo sapiens	63-68
34657149-8	2022	Downstream signaling analysis showed that deletion of PTPN1 or PTPN2 induces resistance to crizotinib by hyperactivating SHP2, the MAPK and JAK/STAT pathways.	Crizotinib	91-101	protein tyrosine phosphatase non-receptor type 11	Homo sapiens	121-125
34657149-8	2022	Downstream signaling analysis showed that deletion of PTPN1 or PTPN2 induces resistance to crizotinib by hyperactivating SHP2, the MAPK and JAK/STAT pathways.	Crizotinib	91-101	signal transducer and activator of transcription 3	Homo sapiens	144-148
34657149-10	2022	Combination of crizotinib with a SHP2 inhibitor synergically inhibited the growth of wild-type or PTPN1/PTPN2 knock-out ALCL, where it reverted TKI resistance.	Crizotinib	15-25	protein tyrosine phosphatase non-receptor type 11	Homo sapiens	33-37
34657149-10	2022	Combination of crizotinib with a SHP2 inhibitor synergically inhibited the growth of wild-type or PTPN1/PTPN2 knock-out ALCL, where it reverted TKI resistance.	Crizotinib	15-25	protein tyrosine phosphatase non-receptor type 1	Homo sapiens	98-103
34657149-10	2022	Combination of crizotinib with a SHP2 inhibitor synergically inhibited the growth of wild-type or PTPN1/PTPN2 knock-out ALCL, where it reverted TKI resistance.	Crizotinib	15-25	protein tyrosine phosphatase non-receptor type 2	Homo sapiens	104-109
34392186-1	2021	INTRODUCTION: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib are approved for advanced non-small-cell lung cancer (NSCLC) with ALK rearrangement.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	14-40
34365406-9	2021	Crizotinib, a MET inhibitor, restored sensitivity to sotorasib by eliminating RAS-MEK-ERK as well as AKT signaling.	Crizotinib	0-10	SAFB like transcription modulator	Homo sapiens	14-17
34365406-9	2021	Crizotinib, a MET inhibitor, restored sensitivity to sotorasib by eliminating RAS-MEK-ERK as well as AKT signaling.	Crizotinib	0-10	mitogen-activated protein kinase kinase 7	Homo sapiens	82-85
34365406-9	2021	Crizotinib, a MET inhibitor, restored sensitivity to sotorasib by eliminating RAS-MEK-ERK as well as AKT signaling.	Crizotinib	0-10	mitogen-activated protein kinase 1	Homo sapiens	86-89
34365406-9	2021	Crizotinib, a MET inhibitor, restored sensitivity to sotorasib by eliminating RAS-MEK-ERK as well as AKT signaling.	Crizotinib	0-10	AKT serine/threonine kinase 1	Homo sapiens	101-104
34722239-3	2021	Crizotinib is an effective ALK inhibitor.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	27-30
34722239-4	2021	In this review paper, we summarized findings from the literature regarding the use of crizotinib for the treatment of sarcoma and sarcomatoid malignancies harboring ALK fusions with definitive partners (with the given gene(s) name) from the years 2010 to 2021.One hundred and four articles were retrieved and after exclusion, 28 studies containing 33 patients were finally selected.	Crizotinib	86-96	ALK receptor tyrosine kinase	Homo sapiens	165-168
34464935-7	2021	3) Novel ERC1-ALK unaligned fusion, a low grade infiltrative deep soft tissue hand sarcoma with prominent-vascularity, myopericytoid/lipofibromatosis-like ovoid cells, and collagenized stroma, was successfully treated with ALK-inhibitor (Crizotinib), avoiding amputation.	Crizotinib	238-248	ALK receptor tyrosine kinase	Homo sapiens	223-226
34766064-5	2021	There was treatment resistance to several lines of conventional local and systemic treatments for peritoneal mesothelioma and biologically targeted MET inhibition with crizotinib.	Crizotinib	168-178	SAFB like transcription modulator	Homo sapiens	148-151
34638496-7	2021	Furthermore, CD74 engagement enhances the cytotoxic effects of conventional chemotherapeutics in ALCL cell lines, as well as the action of the ALK-inhibitor crizotinib in ALK+ ALCL or of CD95 death-receptor signaling in ALK- ALCL.	Crizotinib	157-167	CD74 molecule	Homo sapiens	13-17
34638496-7	2021	Furthermore, CD74 engagement enhances the cytotoxic effects of conventional chemotherapeutics in ALCL cell lines, as well as the action of the ALK-inhibitor crizotinib in ALK+ ALCL or of CD95 death-receptor signaling in ALK- ALCL.	Crizotinib	157-167	ALK receptor tyrosine kinase	Homo sapiens	143-146
34638496-7	2021	Furthermore, CD74 engagement enhances the cytotoxic effects of conventional chemotherapeutics in ALCL cell lines, as well as the action of the ALK-inhibitor crizotinib in ALK+ ALCL or of CD95 death-receptor signaling in ALK- ALCL.	Crizotinib	157-167	ALK receptor tyrosine kinase	Homo sapiens	171-174
34631105-2	2021	Crizotinib is the first tyrosine kinase inhibitor (TKI) against ROS1-rearranged NSCLC.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	64-68
34631105-6	2021	We report an 85-year-old female patient with ROS1-rearranged NSCLC, who developed drug-induced interstitial lung disease (DI-ILD) 2 months after crizotinib treatment, and was treated with prednisolone followed by entrectinib.	Crizotinib	145-155	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	45-49
34392186-12	2021	Compound ALK mutations, which may confer lorlatinib resistance, may occur in crizotinib, ceritinib, and alectinib-resistant lung cancers.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	9-12
34392187-1	2021	PURPOSE: European Organisation for Research and Treatment of Cancer (EORTC) 90101 (CREATE) was a prospective, multicentric, non-randomised, open-label phase II basket trial to assess the efficacy and safety of crizotinib in patients with different types of cancers, including advanced inflammatory myofibroblastic tumour (IMT) with or without anaplastic lymphoma kinase (ALK) rearrangements.	Crizotinib	210-220	ALK receptor tyrosine kinase	Homo sapiens	371-374
34392187-12	2021	CONCLUSION: These updated results confirm previous findings that crizotinib is effective, with durable responses, in patients with locally advanced or metastatic ALK-positive IMT.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	162-165
34392186-1	2021	INTRODUCTION: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib are approved for advanced non-small-cell lung cancer (NSCLC) with ALK rearrangement.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	42-45
34225542-2	2021	Phase III clinical trials have established its superiority to crizotinib in the first-line ALK inhibitor-naive setting.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	91-94
34392186-1	2021	INTRODUCTION: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib are approved for advanced non-small-cell lung cancer (NSCLC) with ALK rearrangement.	Crizotinib	81-91	ALK receptor tyrosine kinase	Homo sapiens	208-211
34392186-6	2021	Five (16%) ALK mutations (L1196M x2, I1171T, D1203N, G1269A/F1174L) and 3 possible bypass mutations (NRAS G12V, EGFR R108K, PIK3CA E545K) were found in 32 crizotinib-resistant cancers.	Crizotinib	155-165	ALK receptor tyrosine kinase	Homo sapiens	11-14
34392186-6	2021	Five (16%) ALK mutations (L1196M x2, I1171T, D1203N, G1269A/F1174L) and 3 possible bypass mutations (NRAS G12V, EGFR R108K, PIK3CA E545K) were found in 32 crizotinib-resistant cancers.	Crizotinib	155-165	NRAS proto-oncogene, GTPase	Homo sapiens	101-105
34392186-6	2021	Five (16%) ALK mutations (L1196M x2, I1171T, D1203N, G1269A/F1174L) and 3 possible bypass mutations (NRAS G12V, EGFR R108K, PIK3CA E545K) were found in 32 crizotinib-resistant cancers.	Crizotinib	155-165	epidermal growth factor receptor	Homo sapiens	112-116
34392186-6	2021	Five (16%) ALK mutations (L1196M x2, I1171T, D1203N, G1269A/F1174L) and 3 possible bypass mutations (NRAS G12V, EGFR R108K, PIK3CA E545K) were found in 32 crizotinib-resistant cancers.	Crizotinib	155-165	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	124-130
34660287-9	2021	Progression-free survival was significantly longer for patients with either concurrent TP53 mutation (n = 17) (6.0 vs. 2.3 vs. 2.9 months, p = 0.009) or EGFR-amp (n = 13) (5.0 vs. 1.2 vs. 2.4 months, p = 0.016) in the EGFR-TKI + crizotinib group than the other two regimen.	Crizotinib	229-239	epidermal growth factor receptor	Homo sapiens	153-157
34559836-13	2021	Indeed through the screening test, we found a novel ALK fusion partner (sperm antigen with calponin homology and coiled-coil domains 1 like gene, SPECC1L) with increased sensitivity to crizotinib in vitro.	Crizotinib	185-195	ALK receptor tyrosine kinase	Homo sapiens	52-55
34339964-3	2021	Here, we present for the first time a drug interaction profile of ALK-TKIs, crizotinib and alectinib, and immunosuppressive agent cyclosporine A in kidney transplant recipients diagnosed with ALK+ lung cancer.	Crizotinib	76-86	ALK receptor tyrosine kinase	Homo sapiens	192-195
34272914-10	2021	A serial assessment identified that ALK L1196M resistance mutation emerged before radiologic progression during crizotinib treatment.	Crizotinib	112-122	ALK receptor tyrosine kinase	Homo sapiens	36-39
34509095-1	2021	Patients with non-small cell lung cancer (NSCLC) harboring ROS proto-oncogene 1 (ROS1) gene rearrangements show dramatic response to the tyrosine kinase inhibitor (TKI) crizotinib.	Crizotinib	169-179	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	81-85
34405544-0	2021	Use of crizotinib as neoadjuvant therapy for non-small cell lung cancers patient with ROS1 rearrangement: A case report.	Crizotinib	7-17	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	86-90
34405544-1	2021	Crizotinib showed significant antitumor effect in patients with advanced ROS1-rearranged non-small cell lung cancers (NSCLC).	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	73-77
34660618-0	2021	Case Report: Two Rare Cases of Complete Metabolic Response to Crizotinib in Patients With Rearranged ROS1 and ALK Metastatic Non-small Lung Cancer.	Crizotinib	62-72	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	101-105
34660618-0	2021	Case Report: Two Rare Cases of Complete Metabolic Response to Crizotinib in Patients With Rearranged ROS1 and ALK Metastatic Non-small Lung Cancer.	Crizotinib	62-72	ALK receptor tyrosine kinase	Homo sapiens	110-113
34660618-1	2021	Crizotinib is a tyrosine kinase inhibitor (TKI) indicated in first-line treatment of rearranged c-ros oncogene 1 (ROS1) and anaplastic lymphoma kinase (ALK) metastatic non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	96-112
34660618-1	2021	Crizotinib is a tyrosine kinase inhibitor (TKI) indicated in first-line treatment of rearranged c-ros oncogene 1 (ROS1) and anaplastic lymphoma kinase (ALK) metastatic non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	114-118
34660618-1	2021	Crizotinib is a tyrosine kinase inhibitor (TKI) indicated in first-line treatment of rearranged c-ros oncogene 1 (ROS1) and anaplastic lymphoma kinase (ALK) metastatic non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	124-150
34660618-1	2021	Crizotinib is a tyrosine kinase inhibitor (TKI) indicated in first-line treatment of rearranged c-ros oncogene 1 (ROS1) and anaplastic lymphoma kinase (ALK) metastatic non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	152-155
34660618-4	2021	We highlighted the 18F-FDG-PET/CT useful approach for therapeutic assessment of TKI in metastatic mutated NSCLC reporting two complete metabolic responses in patients treated with crizotinib for a rearranged ROS1 and a metastatic ALK NSCLC.	Crizotinib	180-190	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	208-212
34630126-0	2021	LINC01001 Promotes Progression of Crizotinib-Resistant NSCLC by Modulating IGF2BP2/MYC Axis.	Crizotinib	34-44	long intergenic non-protein coding RNA 1001	Homo sapiens	0-9
34630126-1	2021	Background: Crizotinib is a microtubule-related protein-4-anaplastic lymphoma kinase (EML4-ALK) multi-target tyrosine kinase inhibitor applied in the treatment of ALK-rearranged NSCLC.	Crizotinib	12-22	EMAP like 4	Homo sapiens	86-90
34630126-1	2021	Background: Crizotinib is a microtubule-related protein-4-anaplastic lymphoma kinase (EML4-ALK) multi-target tyrosine kinase inhibitor applied in the treatment of ALK-rearranged NSCLC.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	91-94
34630126-1	2021	Background: Crizotinib is a microtubule-related protein-4-anaplastic lymphoma kinase (EML4-ALK) multi-target tyrosine kinase inhibitor applied in the treatment of ALK-rearranged NSCLC.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	163-166
34630126-3	2021	Therefore, the purpose of this research is to explore the mechanism by which crizotinib targets NSCLC with ALK-rearrangement, mainly whether it is related to LINC01001 in regulating NSCLC progression via IGF2BP2/MYC axis.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	107-110
34630126-3	2021	Therefore, the purpose of this research is to explore the mechanism by which crizotinib targets NSCLC with ALK-rearrangement, mainly whether it is related to LINC01001 in regulating NSCLC progression via IGF2BP2/MYC axis.	Crizotinib	77-87	long intergenic non-protein coding RNA 1001	Homo sapiens	158-167
34630126-3	2021	Therefore, the purpose of this research is to explore the mechanism by which crizotinib targets NSCLC with ALK-rearrangement, mainly whether it is related to LINC01001 in regulating NSCLC progression via IGF2BP2/MYC axis.	Crizotinib	77-87	insulin like growth factor 2 mRNA binding protein 2	Homo sapiens	204-211
34630126-3	2021	Therefore, the purpose of this research is to explore the mechanism by which crizotinib targets NSCLC with ALK-rearrangement, mainly whether it is related to LINC01001 in regulating NSCLC progression via IGF2BP2/MYC axis.	Crizotinib	77-87	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	212-215
34559836-13	2021	Indeed through the screening test, we found a novel ALK fusion partner (sperm antigen with calponin homology and coiled-coil domains 1 like gene, SPECC1L) with increased sensitivity to crizotinib in vitro.	Crizotinib	185-195	sperm antigen with calponin homology and coiled-coil domains 1 like	Homo sapiens	146-153
34630126-10	2021	Results: Our findings illustrated that LINC01001 is highly expressed in crizotinib-resistant NSCLC cells and associated with poor overall survival of NSCLC patients.	Crizotinib	72-82	long intergenic non-protein coding RNA 1001	Homo sapiens	39-48
34630126-11	2021	Inhibition of LINC01001 depresses crizotinib resistance of NSCLC cells.	Crizotinib	34-44	long intergenic non-protein coding RNA 1001	Homo sapiens	14-23
34516491-0	2021	Combination treatment with trastuzumab and crizotinib in metastatic gastric cancer harboring Her-2 amplification and c-MET amplification: A case report.	Crizotinib	43-53	erb-b2 receptor tyrosine kinase 2	Homo sapiens	93-98
34630126-12	2021	LINC01001 interacts with IGF2BP2, and inhibition of IGF2BP2 depresses crizotinib resistance of NSCLC cells.	Crizotinib	70-80	long intergenic non-protein coding RNA 1001	Homo sapiens	0-9
34630126-12	2021	LINC01001 interacts with IGF2BP2, and inhibition of IGF2BP2 depresses crizotinib resistance of NSCLC cells.	Crizotinib	70-80	insulin like growth factor 2 mRNA binding protein 2	Homo sapiens	52-59
34630126-13	2021	IGF2BP2 interacts with the mRNA of MYC, and LINC01001 overexpression increases crizotinib resistance of NSCLC via MYC.	Crizotinib	79-89	insulin like growth factor 2 mRNA binding protein 2	Homo sapiens	0-7
34630126-13	2021	IGF2BP2 interacts with the mRNA of MYC, and LINC01001 overexpression increases crizotinib resistance of NSCLC via MYC.	Crizotinib	79-89	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	35-38
34630126-13	2021	IGF2BP2 interacts with the mRNA of MYC, and LINC01001 overexpression increases crizotinib resistance of NSCLC via MYC.	Crizotinib	79-89	long intergenic non-protein coding RNA 1001	Homo sapiens	44-53
34630126-13	2021	IGF2BP2 interacts with the mRNA of MYC, and LINC01001 overexpression increases crizotinib resistance of NSCLC via MYC.	Crizotinib	79-89	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	114-117
34630126-14	2021	Conclusion: LINC01001 promotes the progression of crizotinib-resistant NSCLC by modulating the IGF2BP2/MYC axis.	Crizotinib	50-60	long intergenic non-protein coding RNA 1001	Homo sapiens	12-21
34630126-14	2021	Conclusion: LINC01001 promotes the progression of crizotinib-resistant NSCLC by modulating the IGF2BP2/MYC axis.	Crizotinib	50-60	insulin like growth factor 2 mRNA binding protein 2	Homo sapiens	95-102
34630126-14	2021	Conclusion: LINC01001 promotes the progression of crizotinib-resistant NSCLC by modulating the IGF2BP2/MYC axis.	Crizotinib	50-60	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	103-106
34616749-2	2021	Patients with ROS1 fusion have been shown to be highly sensitive to treatment with crizotinib.	Crizotinib	83-93	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	14-18
34616749-9	2021	This case proved that patients with SDC4-ROS1 and ROS1-GK fusions may be sensitive to crizotinib, but short progression-free survival of this case showed that the presence of ROS1-GK rearrangement may affect the efficacy of crizotinib.	Crizotinib	86-96	syndecan 4	Homo sapiens	36-40
34616749-9	2021	This case proved that patients with SDC4-ROS1 and ROS1-GK fusions may be sensitive to crizotinib, but short progression-free survival of this case showed that the presence of ROS1-GK rearrangement may affect the efficacy of crizotinib.	Crizotinib	86-96	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	41-45
34616749-9	2021	This case proved that patients with SDC4-ROS1 and ROS1-GK fusions may be sensitive to crizotinib, but short progression-free survival of this case showed that the presence of ROS1-GK rearrangement may affect the efficacy of crizotinib.	Crizotinib	86-96	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	50-54
34616749-9	2021	This case proved that patients with SDC4-ROS1 and ROS1-GK fusions may be sensitive to crizotinib, but short progression-free survival of this case showed that the presence of ROS1-GK rearrangement may affect the efficacy of crizotinib.	Crizotinib	86-96	glycerol kinase	Homo sapiens	55-57
34616749-9	2021	This case proved that patients with SDC4-ROS1 and ROS1-GK fusions may be sensitive to crizotinib, but short progression-free survival of this case showed that the presence of ROS1-GK rearrangement may affect the efficacy of crizotinib.	Crizotinib	224-234	syndecan 4	Homo sapiens	36-40
34616749-9	2021	This case proved that patients with SDC4-ROS1 and ROS1-GK fusions may be sensitive to crizotinib, but short progression-free survival of this case showed that the presence of ROS1-GK rearrangement may affect the efficacy of crizotinib.	Crizotinib	224-234	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	41-45
34616749-9	2021	This case proved that patients with SDC4-ROS1 and ROS1-GK fusions may be sensitive to crizotinib, but short progression-free survival of this case showed that the presence of ROS1-GK rearrangement may affect the efficacy of crizotinib.	Crizotinib	224-234	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	50-54
34616749-9	2021	This case proved that patients with SDC4-ROS1 and ROS1-GK fusions may be sensitive to crizotinib, but short progression-free survival of this case showed that the presence of ROS1-GK rearrangement may affect the efficacy of crizotinib.	Crizotinib	224-234	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	175-179
34616749-9	2021	This case proved that patients with SDC4-ROS1 and ROS1-GK fusions may be sensitive to crizotinib, but short progression-free survival of this case showed that the presence of ROS1-GK rearrangement may affect the efficacy of crizotinib.	Crizotinib	224-234	glycerol kinase	Homo sapiens	180-182
34552337-0	2021	High Tumor Mutation Burden and DNA Repair Gene Mutations are Associated with Primary Resistance to Crizotinib in ALK-Rearranged Lung Cancer.	Crizotinib	99-109	ALK receptor tyrosine kinase	Homo sapiens	113-116
34552337-6	2021	The effect of the TP53 G245S mutation on crizotinib sensitivity was tested in H3122 cells.	Crizotinib	41-51	tumor protein p53	Homo sapiens	18-22
34552337-11	2021	H3122 cells with TP53 mutant were more sensitive to crizotinib compared with control cells.	Crizotinib	52-62	tumor protein p53	Homo sapiens	17-21
34552337-12	2021	Conclusion: A higher mutation burden and mutations in DNA repair gene, including TP53, were potentially associated with primary resistance to crizotinib in ALK-rearranged NSCLC.	Crizotinib	142-152	tumor protein p53	Homo sapiens	81-85
34552337-12	2021	Conclusion: A higher mutation burden and mutations in DNA repair gene, including TP53, were potentially associated with primary resistance to crizotinib in ALK-rearranged NSCLC.	Crizotinib	142-152	ALK receptor tyrosine kinase	Homo sapiens	156-159
34552337-13	2021	An immune-checkpoint inhibition strategy could be examined, which might overcome primary resistance to crizotinib in ALK-rearranged NSCLC.	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	117-120
34325247-3	2021	Anaplastic lymphoma kinase (ALK) inhibitors, including alectinib (ALC), ceritinib (CER), and crizotinib (CRZ), have been efficiently used in the management of non-small cell lung cancer (NSCLC).	Crizotinib	93-103	ALK receptor tyrosine kinase	Rattus norvegicus	0-26
34325247-3	2021	Anaplastic lymphoma kinase (ALK) inhibitors, including alectinib (ALC), ceritinib (CER), and crizotinib (CRZ), have been efficiently used in the management of non-small cell lung cancer (NSCLC).	Crizotinib	93-103	ALK receptor tyrosine kinase	Rattus norvegicus	28-31
34325247-3	2021	Anaplastic lymphoma kinase (ALK) inhibitors, including alectinib (ALC), ceritinib (CER), and crizotinib (CRZ), have been efficiently used in the management of non-small cell lung cancer (NSCLC).	Crizotinib	105-108	ALK receptor tyrosine kinase	Rattus norvegicus	0-26
34325247-3	2021	Anaplastic lymphoma kinase (ALK) inhibitors, including alectinib (ALC), ceritinib (CER), and crizotinib (CRZ), have been efficiently used in the management of non-small cell lung cancer (NSCLC).	Crizotinib	105-108	ALK receptor tyrosine kinase	Rattus norvegicus	28-31
34685497-0	2021	The Dual Role of Autophagy in Crizotinib-Treated ALK+ ALCL: From the Lymphoma Cells Drug Resistance to Their Demise.	Crizotinib	30-40	ALK receptor tyrosine kinase	Homo sapiens	49-52
34685497-3	2021	Here, we review what is known about autophagy in crizotinib-treated ALK+ ALCL.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	68-71
34530849-1	2021	BACKGROUND: We conducted a study to explore the relationship between pathological cytomorphologic features and the percentage of anaplastic lymphoma kinase (ALK)-positive cells to better predict pulmonary adenocarcinoma prognosis with crizotinib treatment.	Crizotinib	235-245	ALK receptor tyrosine kinase	Homo sapiens	129-155
34530849-1	2021	BACKGROUND: We conducted a study to explore the relationship between pathological cytomorphologic features and the percentage of anaplastic lymphoma kinase (ALK)-positive cells to better predict pulmonary adenocarcinoma prognosis with crizotinib treatment.	Crizotinib	235-245	ALK receptor tyrosine kinase	Homo sapiens	157-160
34530849-12	2021	Signet ring cell cytomorphologic characteristics and the percentage of ALK-positive cells might predict the prognosis of pulmonary adenocarcinoma with crizotinib treatment.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	71-74
34516491-0	2021	Combination treatment with trastuzumab and crizotinib in metastatic gastric cancer harboring Her-2 amplification and c-MET amplification: A case report.	Crizotinib	43-53	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	117-122
34516491-3	2021	Herein, we reported a patient diagnosed with gastric cancer metastasized to multiple bones, along with lymphangitis carcinomatosa in lungs, harboring Her-2 and c-MET amplification with poor PS, positively responded to combinational therapy with trastuzumab and crizotinib.	Crizotinib	261-271	erb-b2 receptor tyrosine kinase 2	Homo sapiens	150-155
34516491-3	2021	Herein, we reported a patient diagnosed with gastric cancer metastasized to multiple bones, along with lymphangitis carcinomatosa in lungs, harboring Her-2 and c-MET amplification with poor PS, positively responded to combinational therapy with trastuzumab and crizotinib.	Crizotinib	261-271	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	160-165
34516491-10	2021	LESSONS: The present case suggested that combinational therapy with trastuzumab and crizotinib might be effective in metastatic gastric cancer patients harboring Her-2 and c-MET amplification, even with a poor PS.	Crizotinib	84-94	erb-b2 receptor tyrosine kinase 2	Homo sapiens	162-167
34516491-10	2021	LESSONS: The present case suggested that combinational therapy with trastuzumab and crizotinib might be effective in metastatic gastric cancer patients harboring Her-2 and c-MET amplification, even with a poor PS.	Crizotinib	84-94	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	172-177
34147645-3	2021	Several clinical trials have demonstrated that ALK-inhibitors (crizotinib, alectinib, brigatinib) show excellent activity also against brain metastases.	Crizotinib	63-73	ALK receptor tyrosine kinase	Homo sapiens	47-50
34511132-0	2021	Clinical and molecular factors that impact the efficacy of first-line crizotinib in ROS1-rearranged non-small-cell lung cancer: a large multicenter retrospective study.	Crizotinib	70-80	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	84-88
34511132-1	2021	BACKGROUND: ROS1-rearranged lung cancers benefit from first-line crizotinib therapy; however, clinical and molecular factors that could affect crizotinib efficacy in ROS1-rearranged lung cancers are not yet well-elucidated.	Crizotinib	65-75	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	12-16
34511132-1	2021	BACKGROUND: ROS1-rearranged lung cancers benefit from first-line crizotinib therapy; however, clinical and molecular factors that could affect crizotinib efficacy in ROS1-rearranged lung cancers are not yet well-elucidated.	Crizotinib	143-153	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	12-16
34511132-1	2021	BACKGROUND: ROS1-rearranged lung cancers benefit from first-line crizotinib therapy; however, clinical and molecular factors that could affect crizotinib efficacy in ROS1-rearranged lung cancers are not yet well-elucidated.	Crizotinib	143-153	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	166-170
34511132-2	2021	Our retrospective study aimed to compare the efficacy of chemotherapy and crizotinib in the first-line treatment of ROS1-rearranged advanced lung cancer and evaluate various clinical and molecular factors that might impact crizotinib efficacy in real-world practice.	Crizotinib	74-84	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	116-120
34511132-6	2021	Patients harboring single CD74-ROS1 (n = 90) had significantly shorter median PFS with crizotinib than those harboring non-CD74 ROS1 fusions (n = 69) (17.0 months vs. 21.0 months; p = 0.008).	Crizotinib	87-97	CD74 molecule	Homo sapiens	26-30
34511132-6	2021	Patients harboring single CD74-ROS1 (n = 90) had significantly shorter median PFS with crizotinib than those harboring non-CD74 ROS1 fusions (n = 69) (17.0 months vs. 21.0 months; p = 0.008).	Crizotinib	87-97	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	31-35
34511132-12	2021	CONCLUSION: Our results demonstrate that baseline brain metastatic status and various molecular factors could contribute to distinct clinical outcomes from first-line crizotinib therapy of patients with ROS1-rearranged lung cancer.	Crizotinib	167-177	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	203-207
34568053-3	2021	We present a 34-year-old young man with ALK rearrangement-positive and KRAS-wild pancreatic cancer who had a remarkable response to crizotinib after resistance to prior chemotherapy and re-response to alectinib after brain metastases developed.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	40-43
34568053-3	2021	We present a 34-year-old young man with ALK rearrangement-positive and KRAS-wild pancreatic cancer who had a remarkable response to crizotinib after resistance to prior chemotherapy and re-response to alectinib after brain metastases developed.	Crizotinib	132-142	KRAS proto-oncogene, GTPase	Homo sapiens	71-75
34503232-3	2021	In these patients, the ALK inhibitor crizotinib achieves high response rates, however 30-40% of them develop further resistance to crizotinib monotherapy, indicating that new therapeutic approaches are needed in this population.	Crizotinib	37-47	ALK receptor tyrosine kinase	Homo sapiens	23-26
34522753-7	2021	Moreover, three patients derived benefit from a second-generation ALK inhibitor after progression of disease or intolerance to the first-generation inhibitor crizotinib.	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	66-69
34124783-5	2021	Among the tested agents, inhibitors of EGFR (BIBX 1382, erlotinib, and afatinib), c-MET (crizotinib), and mTOR (AZD8055) significantly inhibited tumor growth in vivo but did not induce tumor regression.	Crizotinib	89-99	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	82-87
34527107-3	2021	Crizotinib was approved for the first-line therapy of advanced ALK-positive NSCLC patients.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	63-66
34158340-1	2021	Since 2011, with the approval of crizotinib and subsequent approval of four additional targeted therapies, ALK inhibitors have become important treatments for a subset of patients with lung cancer.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	107-110
34124783-6	2021	Co-inhibition of EGFR and c-MET using erlotinib and crizotinib synergistically reduced cell viability in chordoma cell lines but did not result in enhanced in vivo activity.	Crizotinib	52-62	epidermal growth factor receptor	Homo sapiens	17-21
34124783-6	2021	Co-inhibition of EGFR and c-MET using erlotinib and crizotinib synergistically reduced cell viability in chordoma cell lines but did not result in enhanced in vivo activity.	Crizotinib	52-62	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	26-31
34319660-0	2021	A case of lung adenocarcinoma with a novel CD74-ROS1 fusion variant identified by comprehensive genomic profiling that responded to crizotinib and entrectinib.	Crizotinib	132-142	CD74 molecule	Homo sapiens	43-47
34319660-0	2021	A case of lung adenocarcinoma with a novel CD74-ROS1 fusion variant identified by comprehensive genomic profiling that responded to crizotinib and entrectinib.	Crizotinib	132-142	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	48-52
34210658-5	2021	We describe a case of a patient with relapsed, refractory, metastatic ALK F1174L-mutated neuroblastoma who showed no response to the first generation ALK inhibitor crizotinib but had a subsequent complete response to the ALK/ROS1 inhibitor lorlatinib.	Crizotinib	164-174	ALK receptor tyrosine kinase	Homo sapiens	70-73
34484794-6	2021	Our results suggest that crizotinib may provide a promising therapy option for patients with ALK + NSCLC accompanied by alectinib-induced interstitial lung disease.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	93-96
34484794-7	2021	To our knowledge, this is a rare report of successful treatment of ALK + NSCLC with crizotinib after alectinib-induced interstitial lung disease.	Crizotinib	84-94	ALK receptor tyrosine kinase	Homo sapiens	67-70
34490234-9	2021	Additionally, the c-MET inhibitor crizotinib effectively suppressed LC cell proliferation and migration in vitro and in vivo, even with DNM3 depleted.	Crizotinib	34-44	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	18-23
34439291-3	2021	H1993 and H1975 cells were stably transfected with scrambled (shCTRL) or PDK1-targeted (shPDK1) shRNA and then treated with MET inhibitor crizotinib (1 microM), double mutant EGFRL858R/T790M inhibitor WZ4002 (1 microM) or vehicle for 48 h. The effects of PDK1 knockdown on glucose metabolism and apoptosis were evaluated in untreated and TKI-treated cells.	Crizotinib	138-148	SAFB like transcription modulator	Homo sapiens	124-127
34365942-2	2022	Since crizotinib first came out, many ALK inhibitors have come out one after another, but the fatal flaw in each generation of ALK inhibitors is the body"s resistance to drugs.	Crizotinib	6-16	ALK receptor tyrosine kinase	Homo sapiens	127-130
34490099-2	2021	More than 90 different ALK fusion partners have been discovered in NSCLC patients, and ALK tyrosine kinase inhibitors (TKIs) such as crizotinib and alectinib have achieved tumor responses in patients with advanced ALK-positive NSCLC.	Crizotinib	133-143	ALK receptor tyrosine kinase	Homo sapiens	23-26
34490099-2	2021	More than 90 different ALK fusion partners have been discovered in NSCLC patients, and ALK tyrosine kinase inhibitors (TKIs) such as crizotinib and alectinib have achieved tumor responses in patients with advanced ALK-positive NSCLC.	Crizotinib	133-143	ALK receptor tyrosine kinase	Homo sapiens	87-90
34490099-2	2021	More than 90 different ALK fusion partners have been discovered in NSCLC patients, and ALK tyrosine kinase inhibitors (TKIs) such as crizotinib and alectinib have achieved tumor responses in patients with advanced ALK-positive NSCLC.	Crizotinib	133-143	ALK receptor tyrosine kinase	Homo sapiens	214-217
34210658-5	2021	We describe a case of a patient with relapsed, refractory, metastatic ALK F1174L-mutated neuroblastoma who showed no response to the first generation ALK inhibitor crizotinib but had a subsequent complete response to the ALK/ROS1 inhibitor lorlatinib.	Crizotinib	164-174	ALK receptor tyrosine kinase	Homo sapiens	150-153
34098386-5	2021	RESULTS: This study was inspired by the outcome benefit of a parotid cancer patient harbouring ETV6-NTRK3 fusion, who received crizotinib treatment and achieved a 2-year progression-free survival.	Crizotinib	127-137	ETS variant transcription factor 6	Homo sapiens	95-99
34532491-3	2021	MET missense mutations have been demonstrated to mediate resistance to MET-TKIs, such as crizotinib.	Crizotinib	89-99	SAFB like transcription modulator	Homo sapiens	0-3
34532491-3	2021	MET missense mutations have been demonstrated to mediate resistance to MET-TKIs, such as crizotinib.	Crizotinib	89-99	SAFB like transcription modulator	Homo sapiens	71-74
34091214-5	2021	The patient quickly progressed and was found to harbor a MET exon 14 splice site alteration for which she received crizotinib and had a good response.	Crizotinib	115-125	SAFB like transcription modulator	Homo sapiens	57-60
34110462-0	2021	Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR-ABL1 and its resistance and compound mutants BCR-ABL1T315I and BCR-ABL1T315I-E255K.	Crizotinib	0-10	ABL proto-oncogene 1, non-receptor tyrosine kinase	Homo sapiens	19-23
34110462-0	2021	Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR-ABL1 and its resistance and compound mutants BCR-ABL1T315I and BCR-ABL1T315I-E255K.	Crizotinib	0-10	ABL proto-oncogene 1, non-receptor tyrosine kinase	Homo sapiens	116-120
34110462-0	2021	Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR-ABL1 and its resistance and compound mutants BCR-ABL1T315I and BCR-ABL1T315I-E255K.	Crizotinib	0-10	ABL proto-oncogene 1, non-receptor tyrosine kinase	Homo sapiens	183-187
34110462-3	2021	Here we investigated the therapeutic potential of crizotinib, a TKI approved for targeting ALK and ROS1 in non-small cell lung cancer patients, which inhibited also the ABL1 kinase in cell-free systems, for the treatment of advanced and therapy-resistant Ph+ leukemia.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	91-94
34110462-3	2021	Here we investigated the therapeutic potential of crizotinib, a TKI approved for targeting ALK and ROS1 in non-small cell lung cancer patients, which inhibited also the ABL1 kinase in cell-free systems, for the treatment of advanced and therapy-resistant Ph+ leukemia.	Crizotinib	50-60	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	99-103
34110462-3	2021	Here we investigated the therapeutic potential of crizotinib, a TKI approved for targeting ALK and ROS1 in non-small cell lung cancer patients, which inhibited also the ABL1 kinase in cell-free systems, for the treatment of advanced and therapy-resistant Ph+ leukemia.	Crizotinib	50-60	ABL proto-oncogene 1, non-receptor tyrosine kinase	Homo sapiens	169-173
34110462-6	2021	The efficacy of crizotinib was confirmed in vivo in syngeneic mouse models of BCR-ABL1- or BCR-ABL1T315I-driven chronic myeloid leukemia-like disease and in BCR-ABL1-driven acute lymphoblastic leukemia (ALL).	Crizotinib	16-26	c-abl oncogene 1, non-receptor tyrosine kinase	Mus musculus	82-86
34110462-6	2021	The efficacy of crizotinib was confirmed in vivo in syngeneic mouse models of BCR-ABL1- or BCR-ABL1T315I-driven chronic myeloid leukemia-like disease and in BCR-ABL1-driven acute lymphoblastic leukemia (ALL).	Crizotinib	16-26	c-abl oncogene 1, non-receptor tyrosine kinase	Mus musculus	161-165
34098386-5	2021	RESULTS: This study was inspired by the outcome benefit of a parotid cancer patient harbouring ETV6-NTRK3 fusion, who received crizotinib treatment and achieved a 2-year progression-free survival.	Crizotinib	127-137	neurotrophic receptor tyrosine kinase 3	Homo sapiens	100-105
34157012-3	2021	Crizotinib has been effective in ALK and ROS1-positive IMTs but resistance eventually develops.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	33-36
34184417-1	2021	We describe a case of an anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer with development of uterine metastasis after crizotinib and alectinib treatment.	Crizotinib	141-151	ALK receptor tyrosine kinase	Homo sapiens	25-51
34184417-1	2021	We describe a case of an anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer with development of uterine metastasis after crizotinib and alectinib treatment.	Crizotinib	141-151	ALK receptor tyrosine kinase	Homo sapiens	53-56
34272360-4	2021	Multiple lines of evidence plead in favor of specific ICD-inducing effects of crizotinib and ceritinib in ALK-dependent ALCL: (i) they induce ICD stigmata at pharmacologically relevant, low concentrations; (ii) can be mimicked in their ICD-inducing effects by ALK knockdown; (iii) lose their effects in the context of resistance-conferring ALK mutants; (iv) ICD-inducing effects are mimicked by inhibition of the signal transduction pathways operating downstream of ALK.	Crizotinib	78-88	anaplastic lymphoma kinase	Mus musculus	260-263
34272360-4	2021	Multiple lines of evidence plead in favor of specific ICD-inducing effects of crizotinib and ceritinib in ALK-dependent ALCL: (i) they induce ICD stigmata at pharmacologically relevant, low concentrations; (ii) can be mimicked in their ICD-inducing effects by ALK knockdown; (iii) lose their effects in the context of resistance-conferring ALK mutants; (iv) ICD-inducing effects are mimicked by inhibition of the signal transduction pathways operating downstream of ALK.	Crizotinib	78-88	anaplastic lymphoma kinase	Mus musculus	340-343
34272360-4	2021	Multiple lines of evidence plead in favor of specific ICD-inducing effects of crizotinib and ceritinib in ALK-dependent ALCL: (i) they induce ICD stigmata at pharmacologically relevant, low concentrations; (ii) can be mimicked in their ICD-inducing effects by ALK knockdown; (iii) lose their effects in the context of resistance-conferring ALK mutants; (iv) ICD-inducing effects are mimicked by inhibition of the signal transduction pathways operating downstream of ALK.	Crizotinib	78-88	anaplastic lymphoma kinase	Mus musculus	466-469
34076666-14	2021	The repurposing of crizotinib for GOPC-ROS1 Spitz nevi defines a new treatment option for these lesions, particularly in cases for which surgery is relatively contraindicated.	Crizotinib	19-29	golgi associated PDZ and coiled-coil motif containing	Homo sapiens	34-38
34076666-14	2021	The repurposing of crizotinib for GOPC-ROS1 Spitz nevi defines a new treatment option for these lesions, particularly in cases for which surgery is relatively contraindicated.	Crizotinib	19-29	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	39-43
34397683-0	2021	Dramatic response to osimertinib combined with crizotinib in EGFR T790 M mutation only in blood and Met amplification only in tumor tissue expressive non-small cell lung cancer: A case report.	Crizotinib	47-57	epidermal growth factor receptor	Homo sapiens	61-65
34397683-3	2021	PATIENT CONCERNS: A non-smoking 53-year-old male patient with lung adenocarcinoma underwent gefitinib, afatinib, and osimertinib combined with crizotinib treatment and developed different EGFR resistance mutations.	Crizotinib	143-153	epidermal growth factor receptor	Homo sapiens	188-192
34397683-8	2021	LESSONS: Although osimertinib combined with crizotinib therapy showed dramatic tumor shrinkage in both the primary tumor and bone metastasis to an EGFR T790M-mutant NSCLC patient with MET amplification, the progression-free survival (PFS) was only two months.	Crizotinib	44-54	epidermal growth factor receptor	Homo sapiens	147-151
34397683-8	2021	LESSONS: Although osimertinib combined with crizotinib therapy showed dramatic tumor shrinkage in both the primary tumor and bone metastasis to an EGFR T790M-mutant NSCLC patient with MET amplification, the progression-free survival (PFS) was only two months.	Crizotinib	44-54	SAFB like transcription modulator	Homo sapiens	184-187
34322251-0	2021	Response to gefitinib/crizotinib combination in a pulmonary sarcomatoid carcinoma patient harboring concurrent EGFR mutation and MET amplification.	Crizotinib	22-32	epidermal growth factor receptor	Homo sapiens	111-115
34322251-0	2021	Response to gefitinib/crizotinib combination in a pulmonary sarcomatoid carcinoma patient harboring concurrent EGFR mutation and MET amplification.	Crizotinib	22-32	SAFB like transcription modulator	Homo sapiens	129-132
34298655-5	2021	Conversely, as also observed in patients, the crizotinib (anti-MET TKI) and osimertinib combination improved survival and reduced tumor burden in EGFR/MET mice, further validating the model"s value for preclinical studies.	Crizotinib	46-56	SAFB like transcription modulator	Homo sapiens	63-66
34298655-5	2021	Conversely, as also observed in patients, the crizotinib (anti-MET TKI) and osimertinib combination improved survival and reduced tumor burden in EGFR/MET mice, further validating the model"s value for preclinical studies.	Crizotinib	46-56	epidermal growth factor receptor	Homo sapiens	146-150
34298655-5	2021	Conversely, as also observed in patients, the crizotinib (anti-MET TKI) and osimertinib combination improved survival and reduced tumor burden in EGFR/MET mice, further validating the model"s value for preclinical studies.	Crizotinib	46-56	SAFB like transcription modulator	Homo sapiens	151-154
34296007-8	2021	In order to identify the important active sites for the inhibition of the c-Met receptor responsible for the development of cancer cell lines, the crystallized form of the Crizotinib-c-Met complex (PDB code: 2WGJ) is used.	Crizotinib	172-182	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	74-79
34296007-8	2021	In order to identify the important active sites for the inhibition of the c-Met receptor responsible for the development of cancer cell lines, the crystallized form of the Crizotinib-c-Met complex (PDB code: 2WGJ) is used.	Crizotinib	172-182	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	183-188
34230141-7	2021	The inhibition of c-Met by crizotinib reduced ERK activation and Oct4 expression and suppressed CSC properties.	Crizotinib	27-37	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	18-23
34230141-7	2021	The inhibition of c-Met by crizotinib reduced ERK activation and Oct4 expression and suppressed CSC properties.	Crizotinib	27-37	mitogen-activated protein kinase 1	Homo sapiens	46-49
34230141-7	2021	The inhibition of c-Met by crizotinib reduced ERK activation and Oct4 expression and suppressed CSC properties.	Crizotinib	27-37	POU class 5 homeobox 1	Homo sapiens	65-69
34230141-8	2021	CONCLUSION: c-Met and PrPC interact with each other, and targeting c-Met using crizotinib could be a powerful strategy for CRC therapy.	Crizotinib	79-89	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	12-17
34230141-8	2021	CONCLUSION: c-Met and PrPC interact with each other, and targeting c-Met using crizotinib could be a powerful strategy for CRC therapy.	Crizotinib	79-89	prion protein	Homo sapiens	22-26
34230141-8	2021	CONCLUSION: c-Met and PrPC interact with each other, and targeting c-Met using crizotinib could be a powerful strategy for CRC therapy.	Crizotinib	79-89	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	67-72
34157012-3	2021	Crizotinib has been effective in ALK and ROS1-positive IMTs but resistance eventually develops.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	41-45
34234464-0	2021	Durable Response to Crizotinib in a Patient with Pulmonary Adenocarcinoma Harboring MET Intron 14 Mutation: A Case Report.	Crizotinib	20-30	SAFB like transcription modulator	Homo sapiens	84-87
34285770-0	2021	Structural binding site comparisons reveal Crizotinib as a novel LRRK2 inhibitor.	Crizotinib	43-53	leucine rich repeat kinase 2	Homo sapiens	65-70
34262876-1	2021	Background: Brain metastasis is the most common form of tumor recurrence after resistance to crizotinib in patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC).	Crizotinib	93-103	ALK receptor tyrosine kinase	Homo sapiens	121-147
34262876-1	2021	Background: Brain metastasis is the most common form of tumor recurrence after resistance to crizotinib in patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC).	Crizotinib	93-103	ALK receptor tyrosine kinase	Homo sapiens	149-152
34262876-4	2021	Case Presentation: We experienced a patient with ALK-positive NSCLC who developed brain metastasis after crizotinib therapy.	Crizotinib	105-115	ALK receptor tyrosine kinase	Homo sapiens	49-52
34211840-0	2021	Outstanding Response in a Patient With ROS1-Rearranged Inflammatory Myofibroblastic Tumor of Soft Tissues Treated With Crizotinib: Case Report.	Crizotinib	119-129	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	39-43
34211840-0	2021	Outstanding Response in a Patient With ROS1-Rearranged Inflammatory Myofibroblastic Tumor of Soft Tissues Treated With Crizotinib: Case Report.	Crizotinib	119-129	POC1 centriolar protein A	Homo sapiens	93-97
34211840-5	2021	We report the case of a 24-year-old patient with chemotherapy-refractory metastatic IMT harboring ROS1 kinase fusion, who experienced a significant clinical and pathological response to crizotinib.	Crizotinib	186-196	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	98-102
34248545-4	2021	The patient progressed on several lines of therapy, including conventional chemotherapy, pazopanib, and the first-generation ALK inhibitor crizotinib.	Crizotinib	139-149	ALK receptor tyrosine kinase	Homo sapiens	125-128
34235088-0	2021	Peripheral Lung Squamous Carcinoma With ROS1 Rearrangement Sensitive to Crizotinib: A Case Report.	Crizotinib	72-82	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	40-44
34235088-2	2021	In this work, we report a lung squamous cell carcinoma in a patient with peripheral lung cancer radiological manifestation, harboring ROS1 rearrangement, with high sensitivity to crizotinib.	Crizotinib	179-189	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	134-138
34125313-3	2021	RECENT FINDINGS: Four FDA-approved drugs have significant activity against ROS1+ NSCLC: crizotinib, ciritinib, lorlatinib, and entrectinib.	Crizotinib	88-98	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	75-79
34548228-0	2022	A Case Report of Successful Treatment With Crizotinib to Overcome Resistance to Osimertinib in an EGFR Mutated Non-Small-Cell Lung Cancer Patient Harboring an Acquired MET Exon 14 Mutation.	Crizotinib	43-53	epidermal growth factor receptor	Homo sapiens	98-102
34548228-0	2022	A Case Report of Successful Treatment With Crizotinib to Overcome Resistance to Osimertinib in an EGFR Mutated Non-Small-Cell Lung Cancer Patient Harboring an Acquired MET Exon 14 Mutation.	Crizotinib	43-53	SAFB like transcription modulator	Homo sapiens	168-171
34285770-10	2021	While Sunitinib has already been known to inhibit LRRK2, Crizotinib is a novel LRRK2 binder.	Crizotinib	57-67	leucine rich repeat kinase 2	Homo sapiens	79-84
34150615-1	2021	Objective: To systematically evaluate the efficacy and safety of alectinib versus crizotinib in the treatment of anaplastic lymphoma kinase (ALK) positive non-small-cell lung cancer.	Crizotinib	82-92	ALK receptor tyrosine kinase	Homo sapiens	113-139
34168990-3	2021	The patient responded well to the first and second generation of ALK-tyrosine kinase inhibitors (ALK-TKIs) (crizotinib then alectinib), as her imaging findings and clinical symptoms significantly improved.	Crizotinib	108-118	ALK receptor tyrosine kinase	Homo sapiens	65-68
34168990-3	2021	The patient responded well to the first and second generation of ALK-tyrosine kinase inhibitors (ALK-TKIs) (crizotinib then alectinib), as her imaging findings and clinical symptoms significantly improved.	Crizotinib	108-118	ALK receptor tyrosine kinase	Homo sapiens	97-100
34150615-1	2021	Objective: To systematically evaluate the efficacy and safety of alectinib versus crizotinib in the treatment of anaplastic lymphoma kinase (ALK) positive non-small-cell lung cancer.	Crizotinib	82-92	ALK receptor tyrosine kinase	Homo sapiens	141-144
34150615-2	2021	Methods: Studies about the efficacy of alectinib versus crizotinib in the treatment of ALK-positive non-small cell lung cancer were searched in PubMed, Scopus, Embase and the Cocharane Library from inception to February 15, 2020.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	87-90
34589983-0	2021	A Case of Lung Adenocarcinoma Harboring a Rare LOC285000-ALK-NCK2 Gene Fusion Identified by Next-Generation Sequencing With Long-Term Response to Crizotinib.	Crizotinib	146-156	ALK receptor tyrosine kinase	Homo sapiens	57-60
32327503-6	2021	Moreover, inhibition of NOTCH1 with gamma-secretase inhibitors (GSIs) or silencing by shRNA leads to apoptosis; co-treatment in vitro with the ALK inhibitor Crizotinib led to additive/synergistic anti-tumour activity suggesting this may be an appropriate combination therapy for future use in the circumvention of ALK inhibitor resistance.	Crizotinib	157-167	ALK receptor tyrosine kinase	Homo sapiens	143-146
34589977-2	2021	Here, we report, for the first time, a novel, sequentially-evolved EML4-ALK variant 3 G1202R/S1206Y double mutation in cis detected in a patient with ALK-positive NSCLC after disease progression on sequential crizotinib, alectinib, and then lorlatinib.	Crizotinib	209-219	EMAP like 4	Homo sapiens	67-71
34277814-0	2021	Outcomes of switching from crizotinib to alectinib in patients with advanced non-small cell lung cancer with anaplastic lymphoma kinase fusion.	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	109-135
34277814-1	2021	Background: Alectinib and crizotinib have been approved as first-line therapies for advanced non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) gene fusion.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	133-159
34277814-1	2021	Background: Alectinib and crizotinib have been approved as first-line therapies for advanced non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) gene fusion.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	161-164
34094940-0	2021	Crizotinib and Doxorubicin Cooperatively Reduces Drug Resistance by Mitigating MDR1 to Increase Hepatocellular Carcinoma Cells Death.	Crizotinib	0-10	ATP binding cassette subfamily B member 1	Homo sapiens	79-83
34421417-3	2021	The few pediatric reports regarding crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, seem promising.	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	79-82
34421417-4	2021	This case of an 8-year-old male with an ALK-positive anaplastic large cell lymphoma highlights the challenges of treating children with crizotinib.	Crizotinib	136-146	ALK receptor tyrosine kinase	Homo sapiens	40-43
34589977-2	2021	Here, we report, for the first time, a novel, sequentially-evolved EML4-ALK variant 3 G1202R/S1206Y double mutation in cis detected in a patient with ALK-positive NSCLC after disease progression on sequential crizotinib, alectinib, and then lorlatinib.	Crizotinib	209-219	ALK receptor tyrosine kinase	Homo sapiens	72-75
34589977-2	2021	Here, we report, for the first time, a novel, sequentially-evolved EML4-ALK variant 3 G1202R/S1206Y double mutation in cis detected in a patient with ALK-positive NSCLC after disease progression on sequential crizotinib, alectinib, and then lorlatinib.	Crizotinib	209-219	ALK receptor tyrosine kinase	Homo sapiens	150-153
34589983-0	2021	A Case of Lung Adenocarcinoma Harboring a Rare LOC285000-ALK-NCK2 Gene Fusion Identified by Next-Generation Sequencing With Long-Term Response to Crizotinib.	Crizotinib	146-156	NCK adaptor protein 2	Homo sapiens	61-65
34589983-2	2021	We present here a rare LOC285000-ALK-NCK2 gene fusion with response to crizotinib treatment; the patient achieved a progression-free survival of 23 months.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	33-36
34589983-2	2021	We present here a rare LOC285000-ALK-NCK2 gene fusion with response to crizotinib treatment; the patient achieved a progression-free survival of 23 months.	Crizotinib	71-81	NCK adaptor protein 2	Homo sapiens	37-41
35343863-6	2022	Since the approval of crizotinib as multi-targeted ALK/MET/ROS1 kinase inhibitor for ALK-mutated NSCLC therapy, the researchers are focusing on ROS1-mutated tumors, especially NSCLC.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	51-54
35421578-2	2022	Crizotinib, a first generation ALK inhibitor, is widely prescribed for ALK-positive NSCLC in clinic.	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	31-34
35421578-2	2022	Crizotinib, a first generation ALK inhibitor, is widely prescribed for ALK-positive NSCLC in clinic.	Crizotinib	0-10	anaplastic lymphoma kinase	Mus musculus	71-74
35608912-7	2022	Finally, depletion of ALKAL2 in dorsal root ganglia or blocking ALK with clinically available compounds Crizotinib or Lorlatinib, reversed thermal hyperalgesia and mechanical allodynia induced by inflammation or nerve injury, respectively.	Crizotinib	104-114	ALK receptor tyrosine kinase	Homo sapiens	64-67
35118587-15	2022	Crizotinib might be a targeted therapy worthy of exploration in the clinic for metastatic tRCC with PRCC-TFE3 fusion.	Crizotinib	0-10	proline rich mitotic checkpoint control factor	Homo sapiens	100-104
35118587-15	2022	Crizotinib might be a targeted therapy worthy of exploration in the clinic for metastatic tRCC with PRCC-TFE3 fusion.	Crizotinib	0-10	transcription factor binding to IGHM enhancer 3	Homo sapiens	105-109
35343863-6	2022	Since the approval of crizotinib as multi-targeted ALK/MET/ROS1 kinase inhibitor for ALK-mutated NSCLC therapy, the researchers are focusing on ROS1-mutated tumors, especially NSCLC.	Crizotinib	22-32	SAFB like transcription modulator	Homo sapiens	55-58
35343863-6	2022	Since the approval of crizotinib as multi-targeted ALK/MET/ROS1 kinase inhibitor for ALK-mutated NSCLC therapy, the researchers are focusing on ROS1-mutated tumors, especially NSCLC.	Crizotinib	22-32	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	59-63
35343863-6	2022	Since the approval of crizotinib as multi-targeted ALK/MET/ROS1 kinase inhibitor for ALK-mutated NSCLC therapy, the researchers are focusing on ROS1-mutated tumors, especially NSCLC.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	85-88
35614430-0	2022	Failure of crizotinib based systemic treatment in ALK positive histiocytosis involving the central nervous system: a case report and literature review.	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	50-53
35527776-1	2022	Anaplastic lymphoma kinase (ALK) inhibitors have been shown to be effective in treating patients with ALK-positive non-small cell lung cancer (NSCLC), and crizotinib, ceritinib and alectinib have been approved as clinical first-line therapeutic agents.	Crizotinib	155-165	ALK receptor tyrosine kinase	Homo sapiens	0-26
35527776-1	2022	Anaplastic lymphoma kinase (ALK) inhibitors have been shown to be effective in treating patients with ALK-positive non-small cell lung cancer (NSCLC), and crizotinib, ceritinib and alectinib have been approved as clinical first-line therapeutic agents.	Crizotinib	155-165	ALK receptor tyrosine kinase	Homo sapiens	28-31
35437945-0	2022	A CT-based radiomics model to predict subsequent brain metastasis in patients with ALK-rearranged non-small cell lung cancer undergoing crizotinib treatment.	Crizotinib	136-146	ALK receptor tyrosine kinase	Homo sapiens	83-86
35437945-1	2022	BACKGROUND: Brain metastasis (BM) comprises the most common reason for crizotinib failure in patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC).	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	107-133
35437945-1	2022	BACKGROUND: Brain metastasis (BM) comprises the most common reason for crizotinib failure in patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC).	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	135-138
35616090-3	2022	METHODS: Patients with ALK-positive advanced NSCLC, who received crizotinib or alectinib treatment in first line, were retrospectively reviewed.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	23-26
35579888-3	2022	Crizotinib (Cro) is multi-target tyrosine kinase inhibitor targeting ALK gene recombination, MET gene amplification and ROS gene.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	69-72
35579888-3	2022	Crizotinib (Cro) is multi-target tyrosine kinase inhibitor targeting ALK gene recombination, MET gene amplification and ROS gene.	Crizotinib	0-10	SAFB like transcription modulator	Homo sapiens	93-96
35579888-3	2022	Crizotinib (Cro) is multi-target tyrosine kinase inhibitor targeting ALK gene recombination, MET gene amplification and ROS gene.	Crizotinib	12-15	ALK receptor tyrosine kinase	Homo sapiens	69-72
35579888-3	2022	Crizotinib (Cro) is multi-target tyrosine kinase inhibitor targeting ALK gene recombination, MET gene amplification and ROS gene.	Crizotinib	12-15	SAFB like transcription modulator	Homo sapiens	93-96
35619747-0	2022	Unique SLC12A2-ROS1 fusion is associated with marked response to crizotinib in lung adenocarcinoma.	Crizotinib	65-75	solute carrier family 12 member 2	Homo sapiens	7-14
35628598-1	2022	(1) Background: The C-ros oncogene 1 (ROS1) gene translocation is an important biomarker for selecting patients for crizotinib-targeted therapy.	Crizotinib	116-126	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	20-36
35628598-1	2022	(1) Background: The C-ros oncogene 1 (ROS1) gene translocation is an important biomarker for selecting patients for crizotinib-targeted therapy.	Crizotinib	116-126	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	38-42
35628598-2	2022	The aim of this study was to understand the incidence, diagnostic algorithm, clinical course and objective response to crizotinib in ROS1 translocated lung non-small cell lung cancers (NSCLCs) in Taiwan.	Crizotinib	119-129	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	133-137
35628598-11	2022	In these 20 ROS1 translocation cases, 19 patients received crizotinib treatment, with an objective response rate (ORR) of 78.95% (confidence interval = 69.34% to 88.56%), including 1 complete response, 14 partial responses, 3 stable cases and 1 progressive case.	Crizotinib	59-69	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	12-16
35628598-13	2022	(4) Conclusions: ROS1-translocated NSCLCs had a poor prognosis and could have a beneficial outcome with crizotinib.	Crizotinib	104-114	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	17-21
35619747-0	2022	Unique SLC12A2-ROS1 fusion is associated with marked response to crizotinib in lung adenocarcinoma.	Crizotinib	65-75	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	15-19
35619747-3	2022	We herein describe a case of a 26-year-old never-smoker patient from southern Africa with metastatic lung adenocarcinoma driven by SLC12A2-ROS1 fusion, who had a pronounced and durable response to crizotinib.	Crizotinib	197-207	solute carrier family 12 member 2	Homo sapiens	131-138
35619747-3	2022	We herein describe a case of a 26-year-old never-smoker patient from southern Africa with metastatic lung adenocarcinoma driven by SLC12A2-ROS1 fusion, who had a pronounced and durable response to crizotinib.	Crizotinib	197-207	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	139-143
35619747-5	2022	In addition, provides the second report of crizotinib activity against lung malignancies harboring the unique SLC12A2-ROS1 fusion and highlights the importance of a deeper understanding of molecular alterations in underrepresented subgroups of patients to tailor the decision-making in daily practice.	Crizotinib	43-53	solute carrier family 12 member 2	Homo sapiens	110-117
35619747-5	2022	In addition, provides the second report of crizotinib activity against lung malignancies harboring the unique SLC12A2-ROS1 fusion and highlights the importance of a deeper understanding of molecular alterations in underrepresented subgroups of patients to tailor the decision-making in daily practice.	Crizotinib	43-53	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	118-122
35628499-2	2022	The European Organization for Research and Treatment of Cancer (EORTC) 90101 "CREATE" phase II trial evaluated the MET inhibitor crizotinib in ASPS patients, achieving only limited antitumor activity.	Crizotinib	129-139	SAFB like transcription modulator	Homo sapiens	115-118
35628499-2	2022	The European Organization for Research and Treatment of Cancer (EORTC) 90101 "CREATE" phase II trial evaluated the MET inhibitor crizotinib in ASPS patients, achieving only limited antitumor activity.	Crizotinib	129-139	ASPSCR1 tether for SLC2A4, UBX domain containing	Homo sapiens	143-147
35628499-15	2022	NOTCH4 intracellular domain dysregulation was associated with poor outcome, while inactivation of the beta-catenin/TCF complex correlated with improved outcome in patients receiving crizotinib.	Crizotinib	182-192	catenin beta 1	Homo sapiens	102-114
35568279-0	2022	Durable response to crizotinib in metastatic angiomatoid fibrous histiocytoma with EWSR1-CREB1 fusion and ALK overexpression.	Crizotinib	20-30	EWS RNA binding protein 1	Homo sapiens	83-88
35568279-0	2022	Durable response to crizotinib in metastatic angiomatoid fibrous histiocytoma with EWSR1-CREB1 fusion and ALK overexpression.	Crizotinib	20-30	cAMP responsive element binding protein 1	Homo sapiens	89-94
35560808-1	2022	BACKGROUND: The efficacy difference between the second- and third-generation of anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) after crizotinib failure in advanced ALK-positive non-small cell lung cancer (NSCLC) has not been clarified.	Crizotinib	151-161	ALK receptor tyrosine kinase	Homo sapiens	182-185
35568279-0	2022	Durable response to crizotinib in metastatic angiomatoid fibrous histiocytoma with EWSR1-CREB1 fusion and ALK overexpression.	Crizotinib	20-30	ALK receptor tyrosine kinase	Homo sapiens	106-109
35625997-2	2022	ALK and c-MET inhibition with crizotinib have a preclinical therapeutic rationale to be tested in newly diagnosed GBM.	Crizotinib	30-40	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	8-13
35574423-0	2022	Case Report: Short-Term Response to First-Line Crizotinib Monotherapy in a Metastatic Lung Adenocarcinoma Patient Harboring a Novel TPR-ROS1 Fusion.	Crizotinib	47-57	translocated promoter region, nuclear basket protein	Homo sapiens	132-135
35551560-0	2022	A lung adenocarcinoma patient harboring MET c. 3028 + 2 T >A variant sensitive to crizotinib treatment.	Crizotinib	82-92	SAFB like transcription modulator	Homo sapiens	40-43
35551560-1	2022	Several studies have reported that patients harboring MET-ex14 skipping benefit from MET tyrosine kinase inhibitors (TKIs) such as crizotinib, however, the overall response of crizotinib was 32% in these patients.	Crizotinib	131-141	SAFB like transcription modulator	Homo sapiens	54-57
35551560-1	2022	Several studies have reported that patients harboring MET-ex14 skipping benefit from MET tyrosine kinase inhibitors (TKIs) such as crizotinib, however, the overall response of crizotinib was 32% in these patients.	Crizotinib	131-141	SAFB like transcription modulator	Homo sapiens	85-88
35551560-1	2022	Several studies have reported that patients harboring MET-ex14 skipping benefit from MET tyrosine kinase inhibitors (TKIs) such as crizotinib, however, the overall response of crizotinib was 32% in these patients.	Crizotinib	176-186	SAFB like transcription modulator	Homo sapiens	54-57
35551560-1	2022	Several studies have reported that patients harboring MET-ex14 skipping benefit from MET tyrosine kinase inhibitors (TKIs) such as crizotinib, however, the overall response of crizotinib was 32% in these patients.	Crizotinib	176-186	SAFB like transcription modulator	Homo sapiens	85-88
35510711-4	2022	METHODS: In a retrospective analysis of ROS1- and ALK-rearranged NSCLCs treated with crizotinib in a phase 1 trial, we compared progression-free survival (PFS) and objective response rate (ORR) based on the history of anticoagulation use (a possible surrogate of thromboembolism) at baseline (within 90 days before study enrollment) or within 90 days of study treatment.	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	50-53
35510711-9	2022	CONCLUSIONS: Anticoagulation (as a potential surrogate of a prothrombotic subset) in ROS1- and ALK-rearranged NSCLCs may be associated with a lower PFS and ORR to crizotinib.	Crizotinib	163-173	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	85-89
35149545-8	2022	Combinatorial treatment of mitochondrial inhibitors with crizotinib revealed inhibitory synergism, suggesting increased reliance on glutamine metabolism and fatty-acid synthesis in chronic ROS1-TKI treated LUAD-0006 cells.	Crizotinib	57-67	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	189-193
35023290-12	2022	Finally, high CNTNAP1 expression was negatively correlated with Nilotinib, Crizotinib, Eribulin mesylate, and Vinorelbine.	Crizotinib	75-85	contactin associated protein 1	Homo sapiens	14-21
35543963-1	2022	INTRODUCTION: MET exon 14 skipping in patients with advanced non-small cell lung cancer (aNSCLC), can be targeted with MET inhibitors including tepotinib, capmatinib, savolitinib, and crizotinib.	Crizotinib	184-194	SAFB like transcription modulator	Homo sapiens	14-17
35543963-1	2022	INTRODUCTION: MET exon 14 skipping in patients with advanced non-small cell lung cancer (aNSCLC), can be targeted with MET inhibitors including tepotinib, capmatinib, savolitinib, and crizotinib.	Crizotinib	184-194	SAFB like transcription modulator	Homo sapiens	119-122
35405360-1	2022	BACKGROUND: Programmed cell death-ligand 1 (PD-L1) expression has been associated with shorter progression-free survival (PFS) of crizotinib-treated patients with anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC).	Crizotinib	130-140	CD274 molecule	Homo sapiens	12-42
35405360-1	2022	BACKGROUND: Programmed cell death-ligand 1 (PD-L1) expression has been associated with shorter progression-free survival (PFS) of crizotinib-treated patients with anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC).	Crizotinib	130-140	CD274 molecule	Homo sapiens	44-49
35405360-1	2022	BACKGROUND: Programmed cell death-ligand 1 (PD-L1) expression has been associated with shorter progression-free survival (PFS) of crizotinib-treated patients with anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC).	Crizotinib	130-140	ALK receptor tyrosine kinase	Homo sapiens	163-189
35405360-1	2022	BACKGROUND: Programmed cell death-ligand 1 (PD-L1) expression has been associated with shorter progression-free survival (PFS) of crizotinib-treated patients with anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC).	Crizotinib	130-140	ALK receptor tyrosine kinase	Homo sapiens	191-194
35405360-4	2022	METHODS: Between October 1, 2015, and October 31, 2021, we retrospectively analyzed the baseline PD-L1 expression levels using immunohistochemistry 22C3 assay of tissue samples from 128 patients with ALK-rearranged advanced lung adenocarcinoma who were treated with first-line crizotinib.	Crizotinib	277-287	CD274 molecule	Homo sapiens	97-102
35405360-7	2022	Patients with high baseline PD-L1 (n = 30) expression level had significantly shorter median PFS (6 vs 11 months, p = 0.011) and OS (17 vs 53 months, p = 0.023) on crizotinib treatment than those with low PD-L1 level (n = 98).	Crizotinib	164-174	CD274 molecule	Homo sapiens	28-33
35405360-7	2022	Patients with high baseline PD-L1 (n = 30) expression level had significantly shorter median PFS (6 vs 11 months, p = 0.011) and OS (17 vs 53 months, p = 0.023) on crizotinib treatment than those with low PD-L1 level (n = 98).	Crizotinib	164-174	CD274 molecule	Homo sapiens	205-210
35574423-0	2022	Case Report: Short-Term Response to First-Line Crizotinib Monotherapy in a Metastatic Lung Adenocarcinoma Patient Harboring a Novel TPR-ROS1 Fusion.	Crizotinib	47-57	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	136-140
35574423-3	2022	Herein, we report a patient with stage IV NSCLC that harbored a novel TPR-ROS1 fusion, which demonstrated a rapid but short partial response to first line crizotinib and primary resistance to subsequent ceritinib.	Crizotinib	155-165	translocated promoter region, nuclear basket protein	Homo sapiens	70-73
35574423-3	2022	Herein, we report a patient with stage IV NSCLC that harbored a novel TPR-ROS1 fusion, which demonstrated a rapid but short partial response to first line crizotinib and primary resistance to subsequent ceritinib.	Crizotinib	155-165	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	74-78
35466809-5	2022	CASE REPORT: We present a case of pulmonary embolism (PE) and bradycardia in a 91-year-old NSCLC patient treated with crizotinib for a rare MET Y1003S mutation.	Crizotinib	118-128	SAFB like transcription modulator	Homo sapiens	140-143
35463328-2	2022	After the approval of the first-generation ALK inhibitor crizotinib which achieved better results in prolonging the progression-free survival (PFS) compared with chemotherapy, a number of next-generation ALK inhibitors have been developed including ceritinib, alectinib, brigatinib, and ensartinib.	Crizotinib	57-67	ALK receptor tyrosine kinase	Homo sapiens	43-46
35437925-7	2022	Eight patients developed ALK resistance mutations after crizotinib therapy; L1196M (n = 5), G1269A (n = 1), G1202R (n = 1), and co-occurring F1174L, G1202R, and G1269A (n = 1).	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	25-28
35446297-5	2022	INTERVENTIONS AND OUTCOMES: The patient was administered oral crizotinib (250 mg bid) combined with endostar (30 mg d1-7) for 12 cycles from June 18, 2020.	Crizotinib	62-72	BH3 interacting domain death agonist	Homo sapiens	81-84
35446297-12	2022	In our case, a novel CLHC1/RNT4 intergenic region, ALK fusion, was identified for the first time in a lung adenocarcinoma patient with BM, who benefited from crizotinib and endostar sequential alectinib.	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	51-54
35171116-0	2022	Dramatic response to crizotinib in a breast cancer patient with ALK gene rearrangement.	Crizotinib	21-31	ALK receptor tyrosine kinase	Homo sapiens	64-67
35066105-10	2022	A combination treatment concomitantly targeting the two driver alterations was required on the corresponding patient-derived models to restore cell sensitivity, which was consistent with clinical data showing efficacy of brigatinib in the patient with ALK fusion after progression to osimertinib and crizotinib administered sequentially.	Crizotinib	300-310	ALK receptor tyrosine kinase	Homo sapiens	252-255
35361870-0	2022	Disease progression patterns and molecular resistance mechanisms to crizotinib of lung adenocarcinoma harboring ROS1 rearrangements.	Crizotinib	68-78	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	112-116
35373538-1	2022	A 44-year-old woman with ALK-positive advanced adenocarcinoma of the lung was treated with crizotinib, and the lung lesions disappeared.	Crizotinib	91-101	ALK receptor tyrosine kinase	Homo sapiens	25-28
35361870-1	2022	This retrospective study investigated the association between the pattern of disease progression and molecular mechanism of acquired resistance in a large cohort of 49 patients with ROS1-rearranged advanced non-small-cell lung cancer treated with first-line crizotinib.	Crizotinib	258-268	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	182-186
35361870-2	2022	We found that treatment-emergent ROS1 point mutations were the major molecular mechanism of crizotinib resistance, particularly for patients who developed extracranial-only disease progression.	Crizotinib	92-102	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	33-37
35529295-0	2022	Multiple Brain Metastases in a Patient with ROS1 Fusion-Positive Lung Adenocarcinoma as a Disease Flare due to Crizotinib Cessation Caused by Disseminated Aseptic Inflammation from Crizotinib-Associated Renal Cysts: A Case Report.	Crizotinib	111-121	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	44-48
35529295-0	2022	Multiple Brain Metastases in a Patient with ROS1 Fusion-Positive Lung Adenocarcinoma as a Disease Flare due to Crizotinib Cessation Caused by Disseminated Aseptic Inflammation from Crizotinib-Associated Renal Cysts: A Case Report.	Crizotinib	181-191	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	44-48
35529295-5	2022	Although crizotinib, an ROS1 tyrosine kinase inhibitor, achieved a partial response, a mass lesion appeared in the patient"s right kidney 12 months after starting crizotinib, which was diagnosed pathologically as crizotinib-associated renal cysts (CARCs).	Crizotinib	9-19	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	24-28
35092185-4	2022	Crizotinib is the first ALK inhibitor approved by the FDA.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	24-27
35324532-3	2022	One study identified MNNG HOS transforming (MET) amplification as intrinsic or secondary resistance mechanism from four patients, and three of them showed ~40% tumor reduction when treated with selpercatinib plus crizotinib.	Crizotinib	213-223	SAFB like transcription modulator	Homo sapiens	44-47
35324532-7	2022	MNNG HOS transforming (MET) amplification was subsequently detected upon progression on selpercatinib, and the patient was placed on third-line treatment with selpercatinib plus crizotinib.	Crizotinib	178-188	SAFB like transcription modulator	Homo sapiens	23-26
35324532-10	2022	In addition, the apparent lack of response to selpercatinib plus crizotinib in this case highlights the need for future cohort studies for examining the value of combining RET and MET inhibitors in treating RET-rearranged, MET-amplified NSCLC.	Crizotinib	65-75	ret proto-oncogene	Homo sapiens	172-175
35324532-10	2022	In addition, the apparent lack of response to selpercatinib plus crizotinib in this case highlights the need for future cohort studies for examining the value of combining RET and MET inhibitors in treating RET-rearranged, MET-amplified NSCLC.	Crizotinib	65-75	SAFB like transcription modulator	Homo sapiens	223-226
35359354-9	2022	Subsequently, the patient received chemotherapy (CHOP regimen) and anti-ALK therapy (crizotinib).	Crizotinib	85-95	ALK receptor tyrosine kinase	Homo sapiens	72-75
35105467-2	2022	The Food and Drug Administration and European Medicines Agency have approved several inhibitors for the treatment of non-small cell lung cancer : five tyrosine kinase inhibitors targeting EGFR (erlotinib, gefitinib, afatinib, osimertinib and dacomitinib) and six tyrosine kinase inhibitors targeting ALK (crizotinib, ceritinib, alectinib, brigatinib, lorlatinib and entrectinib).	Crizotinib	305-315	epidermal growth factor receptor	Homo sapiens	188-192
35433411-4	2022	Here, we present the case of choroidal metastases secondary to lung cancer and EML4-ALK translocation in a 57-year-old woman who firstly underwent resection of lung lesions followed by oral administration of crizotinib without local treatment or systemic chemotherapy.	Crizotinib	208-218	EMAP like 4	Homo sapiens	79-83
35433411-4	2022	Here, we present the case of choroidal metastases secondary to lung cancer and EML4-ALK translocation in a 57-year-old woman who firstly underwent resection of lung lesions followed by oral administration of crizotinib without local treatment or systemic chemotherapy.	Crizotinib	208-218	ALK receptor tyrosine kinase	Homo sapiens	84-87
35434049-0	2022	Effective response to crizotinib of concurrent KIF5B-MET and MET-CDR2-rearranged non-small cell lung cancer: A case report.	Crizotinib	22-32	kinesin family member 5B	Homo sapiens	47-52
35434049-0	2022	Effective response to crizotinib of concurrent KIF5B-MET and MET-CDR2-rearranged non-small cell lung cancer: A case report.	Crizotinib	22-32	SAFB like transcription modulator	Homo sapiens	53-56
35434049-0	2022	Effective response to crizotinib of concurrent KIF5B-MET and MET-CDR2-rearranged non-small cell lung cancer: A case report.	Crizotinib	22-32	SAFB like transcription modulator	Homo sapiens	61-64
35434049-0	2022	Effective response to crizotinib of concurrent KIF5B-MET and MET-CDR2-rearranged non-small cell lung cancer: A case report.	Crizotinib	22-32	cerebellar degeneration related protein 2	Homo sapiens	65-69
35434049-1	2022	BACKGROUND: Due to the rarity of mesenchymal-epithelial transition factor (MET) fusions, the clinical efficacy of crizotinib has only been described in a few patients with MET fusions involving various fusion partners.	Crizotinib	114-124	SAFB like transcription modulator	Homo sapiens	33-73
35434049-1	2022	BACKGROUND: Due to the rarity of mesenchymal-epithelial transition factor (MET) fusions, the clinical efficacy of crizotinib has only been described in a few patients with MET fusions involving various fusion partners.	Crizotinib	114-124	SAFB like transcription modulator	Homo sapiens	75-78
35434049-1	2022	BACKGROUND: Due to the rarity of mesenchymal-epithelial transition factor (MET) fusions, the clinical efficacy of crizotinib has only been described in a few patients with MET fusions involving various fusion partners.	Crizotinib	114-124	SAFB like transcription modulator	Homo sapiens	172-175
35434049-2	2022	Herein, we report the clinical response to crizotinib of a patient with advanced poorly differentiated non-small cell carcinoma (NSCLC) having concurrent MET fusions.	Crizotinib	43-53	SAFB like transcription modulator	Homo sapiens	154-157
35434049-9	2022	CONCLUSION: Crizotinib sensitivity was observed in an advanced poorly differentiated NSCLC patient with concurrent MET fusions KIF5B-MET and MET-CDR2.	Crizotinib	12-22	SAFB like transcription modulator	Homo sapiens	115-118
35434049-9	2022	CONCLUSION: Crizotinib sensitivity was observed in an advanced poorly differentiated NSCLC patient with concurrent MET fusions KIF5B-MET and MET-CDR2.	Crizotinib	12-22	kinesin family member 5B	Homo sapiens	127-132
35434049-9	2022	CONCLUSION: Crizotinib sensitivity was observed in an advanced poorly differentiated NSCLC patient with concurrent MET fusions KIF5B-MET and MET-CDR2.	Crizotinib	12-22	SAFB like transcription modulator	Homo sapiens	133-136
35434049-9	2022	CONCLUSION: Crizotinib sensitivity was observed in an advanced poorly differentiated NSCLC patient with concurrent MET fusions KIF5B-MET and MET-CDR2.	Crizotinib	12-22	SAFB like transcription modulator	Homo sapiens	141-144
35434049-9	2022	CONCLUSION: Crizotinib sensitivity was observed in an advanced poorly differentiated NSCLC patient with concurrent MET fusions KIF5B-MET and MET-CDR2.	Crizotinib	12-22	cerebellar degeneration related protein 2	Homo sapiens	145-149
35434049-10	2022	Crizotinib can serve as a therapeutic option for patients with MET fusions.	Crizotinib	0-10	SAFB like transcription modulator	Homo sapiens	63-66
35277956-9	2022	We then present an analysis that identifies sensitivity to the drug crizotinib for cells harboring EML4-ALK or NPM1-ALK gene fusions, as well as significantly down-regulated cell-matrix pathways associated with crizotinib sensitivity.	Crizotinib	68-78	EMAP like 4	Homo sapiens	99-103
35277956-9	2022	We then present an analysis that identifies sensitivity to the drug crizotinib for cells harboring EML4-ALK or NPM1-ALK gene fusions, as well as significantly down-regulated cell-matrix pathways associated with crizotinib sensitivity.	Crizotinib	68-78	ALK receptor tyrosine kinase	Homo sapiens	104-107
35277956-9	2022	We then present an analysis that identifies sensitivity to the drug crizotinib for cells harboring EML4-ALK or NPM1-ALK gene fusions, as well as significantly down-regulated cell-matrix pathways associated with crizotinib sensitivity.	Crizotinib	68-78	nucleophosmin 1	Homo sapiens	111-115
35277956-9	2022	We then present an analysis that identifies sensitivity to the drug crizotinib for cells harboring EML4-ALK or NPM1-ALK gene fusions, as well as significantly down-regulated cell-matrix pathways associated with crizotinib sensitivity.	Crizotinib	68-78	ALK receptor tyrosine kinase	Homo sapiens	116-119
35092185-7	2022	CONCLUSION: Crizotinib can be extremely effective in adolescents with treatment-naive ALK-positive NSCLC but fail to prevent a central nervous system relapse.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	86-89
35233056-0	2022	Crizotinib in patients with tumors harboring ALK or ROS1 rearrangements in the NCI-MATCH trial.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	45-48
35299735-0	2022	Case Report: Adjuvant Crizotinib Therapy Exerted Favorable Survival Benefit in a Resectable Stage IIIA NSCLC Patient With Novel LDLR-ROS1 Fusion.	Crizotinib	22-32	low density lipoprotein receptor	Homo sapiens	128-132
35299735-0	2022	Case Report: Adjuvant Crizotinib Therapy Exerted Favorable Survival Benefit in a Resectable Stage IIIA NSCLC Patient With Novel LDLR-ROS1 Fusion.	Crizotinib	22-32	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	133-137
35299735-6	2022	In this case, we report a novel LDLR-ROS1 fusion responding to crizotinib in a patient with lung adenocarcinoma, supporting the use of adjuvant treatment with the ROS1 inhibitor exerting clinical survival benefit in ROS1 fusion-positive resected NSCLC.	Crizotinib	63-73	low density lipoprotein receptor	Homo sapiens	32-36
35299735-6	2022	In this case, we report a novel LDLR-ROS1 fusion responding to crizotinib in a patient with lung adenocarcinoma, supporting the use of adjuvant treatment with the ROS1 inhibitor exerting clinical survival benefit in ROS1 fusion-positive resected NSCLC.	Crizotinib	63-73	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	37-41
35299735-6	2022	In this case, we report a novel LDLR-ROS1 fusion responding to crizotinib in a patient with lung adenocarcinoma, supporting the use of adjuvant treatment with the ROS1 inhibitor exerting clinical survival benefit in ROS1 fusion-positive resected NSCLC.	Crizotinib	63-73	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	216-220
35233056-0	2022	Crizotinib in patients with tumors harboring ALK or ROS1 rearrangements in the NCI-MATCH trial.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	52-56
35233056-11	2022	We observed responses to crizotinib which met the primary endpoint for ALK fusions, albeit in a small number of patients.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	71-74
35506104-0	2022	Crizotinib for ROS1-rearranged lung cancer and pulmonary tumor thrombotic microangiopathy under venoarterial extracorporeal membrane oxygenation.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	15-19
35506104-4	2022	Crizotinib, an oral tyrosine kinase inhibitor targeting anaplastic lymphoma kinase, MET, and ROS1 kinase domains dramatically resolved PH, resulting in more than 3 years of survival.	Crizotinib	0-10	SAFB like transcription modulator	Homo sapiens	84-87
35506104-4	2022	Crizotinib, an oral tyrosine kinase inhibitor targeting anaplastic lymphoma kinase, MET, and ROS1 kinase domains dramatically resolved PH, resulting in more than 3 years of survival.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	93-97
35237515-0	2022	Case Report: Dramatic Response to Crizotinib in a Patient With Non-Small Cell Lung Cancer Positive for a Novel ARL1-MET Fusion.	Crizotinib	34-44	ADP ribosylation factor like GTPase 1	Homo sapiens	111-115
35164578-3	2022	A positive ALK evaluation has therapeutic implications as both tumors responded to single-agent treatment with the tyrosine kinase inhibitor crizotinib.	Crizotinib	141-151	ALK receptor tyrosine kinase	Homo sapiens	11-14
35237506-5	2022	We herein report the first case of PRRC2B-ALK fusion associated IMTs with clinical and pathological manifestation matched the diagnosis criteria of EIMS and the durable clinical response of the sequential use of ALK TKIs (crizotinib, alectinib, ceritinib, and lorlatinib).	Crizotinib	222-232	proline rich coiled-coil 2B	Homo sapiens	35-41
35237515-0	2022	Case Report: Dramatic Response to Crizotinib in a Patient With Non-Small Cell Lung Cancer Positive for a Novel ARL1-MET Fusion.	Crizotinib	34-44	SAFB like transcription modulator	Homo sapiens	116-119
35237506-5	2022	We herein report the first case of PRRC2B-ALK fusion associated IMTs with clinical and pathological manifestation matched the diagnosis criteria of EIMS and the durable clinical response of the sequential use of ALK TKIs (crizotinib, alectinib, ceritinib, and lorlatinib).	Crizotinib	222-232	ALK receptor tyrosine kinase	Homo sapiens	42-45
35144623-0	2022	Concomitant novel ALK-SSH2, EML4-ALK and ARID2-ALK, EML4-ALK double-fusion variants and confer sensitivity to crizotinib in two lung adenocarcinoma patients, respectively.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	18-21
35237506-7	2022	Crizotinib was administered when PRRC2B-ALK fusion was detected, and partial response was achieved.	Crizotinib	0-10	proline rich coiled-coil 2B	Homo sapiens	33-39
35237506-7	2022	Crizotinib was administered when PRRC2B-ALK fusion was detected, and partial response was achieved.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	40-43
35144623-0	2022	Concomitant novel ALK-SSH2, EML4-ALK and ARID2-ALK, EML4-ALK double-fusion variants and confer sensitivity to crizotinib in two lung adenocarcinoma patients, respectively.	Crizotinib	110-120	slingshot protein phosphatase 2	Homo sapiens	22-26
35144623-0	2022	Concomitant novel ALK-SSH2, EML4-ALK and ARID2-ALK, EML4-ALK double-fusion variants and confer sensitivity to crizotinib in two lung adenocarcinoma patients, respectively.	Crizotinib	110-120	EMAP like 4	Homo sapiens	28-32
35144623-0	2022	Concomitant novel ALK-SSH2, EML4-ALK and ARID2-ALK, EML4-ALK double-fusion variants and confer sensitivity to crizotinib in two lung adenocarcinoma patients, respectively.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	33-36
35144623-0	2022	Concomitant novel ALK-SSH2, EML4-ALK and ARID2-ALK, EML4-ALK double-fusion variants and confer sensitivity to crizotinib in two lung adenocarcinoma patients, respectively.	Crizotinib	110-120	AT-rich interaction domain 2	Homo sapiens	41-46
35144623-0	2022	Concomitant novel ALK-SSH2, EML4-ALK and ARID2-ALK, EML4-ALK double-fusion variants and confer sensitivity to crizotinib in two lung adenocarcinoma patients, respectively.	Crizotinib	110-120	EMAP like 4	Homo sapiens	52-56
35144623-0	2022	Concomitant novel ALK-SSH2, EML4-ALK and ARID2-ALK, EML4-ALK double-fusion variants and confer sensitivity to crizotinib in two lung adenocarcinoma patients, respectively.	Crizotinib	110-120	ALK receptor tyrosine kinase	Homo sapiens	57-60
35144623-9	2022	Both of these patients responded to ALK inhibitor crizotinib.	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	36-39
35284560-0	2022	ROS1 fusion lung adenosquamous carcinoma patient with short-term clinical benefit after crizotinib treatment: a case report.	Crizotinib	88-98	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	0-4
35368001-0	2022	ROS1-Rearranged Lung Cancer Successfully Resected after Response to Crizotinib: A Case Report.	Crizotinib	68-78	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	0-4
35368001-2	2022	We present the case of ROS1- rearranged lung cancer successfully resected after response to crizotinib.	Crizotinib	92-102	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	23-27
35252896-2	2022	ROS1 rearrangement has been observed in only 2% of cases of NSCLC and has been successfully targeted using various tyrosine kinase inhibitors including crizotinib.	Crizotinib	152-162	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	0-4
35252896-4	2022	Here, we report a case of a patient with ROS1 rearranged NSCLC presenting primary resistance to crizotinib.	Crizotinib	96-106	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	41-45
35284560-2	2022	Crizotinib is known to be effective in patients with ROS1-rearranged NSCLC.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	53-57
35284560-11	2022	This is the first case report of response to crizotinib for a lung ASC patient with ROS1 fusion, and may help future targeted therapy investigations and prognostic evaluation for patients with rare pathological subtypes of NSCLC.	Crizotinib	45-55	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	84-88
35108034-0	2022	Treatment of Disseminated Intravenous Leiomyomatosis With ALK Targeting Crizotinib: A Successful Case Report.	Crizotinib	72-82	ALK receptor tyrosine kinase	Homo sapiens	58-61
35174181-11	2021	Conclusion: The MET Y1003S mutation was detected in this case, and the patient achieved a partial response using crizotinib.	Crizotinib	113-123	SAFB like transcription modulator	Homo sapiens	16-19
35110965-0	2022	Treatment Response to Immunotherapy After Crizotinib Resistance in a Patient With Pulmonary Sarcomatoid Carcinoma Harboring MET Exon 14 Skipping Mutation: A Case Report.	Crizotinib	42-52	SAFB like transcription modulator	Homo sapiens	124-127
35155225-8	2022	Crizotinib and sunitinib induced apoptosis via the mitochondrial pathway, which was characterized by decreasing Bcl2/Bax ratio to dissipate the mitochondrial membrane potential, and increasing apoptotic markers levels.	Crizotinib	0-10	BCL2 apoptosis regulator	Homo sapiens	112-116
35155225-8	2022	Crizotinib and sunitinib induced apoptosis via the mitochondrial pathway, which was characterized by decreasing Bcl2/Bax ratio to dissipate the mitochondrial membrane potential, and increasing apoptotic markers levels.	Crizotinib	0-10	BCL2 associated X, apoptosis regulator	Homo sapiens	117-120
35155225-10	2022	Taken together, this study demonstrated that crizotinib- and sunitinib-caused oxidative stress and apoptosis finally impaired hepatic function, which was strongly supported by the histopathological lesions and markedly increased levels of serum alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase.	Crizotinib	45-55	glutamic--pyruvic transaminase	Homo sapiens	245-269
35200557-5	2022	More recently developed are ROS-1-targeting TKIs that are active against resistance mechanisms appearing under crizotinib and have better brain penetration.	Crizotinib	111-121	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	28-33
35087031-11	2022	For patients who were ALK-rearranged and ALK TKI naive, the ORR were 81.0% (17 of 21) in the dose-escalation phase and 76.3% (29 of 38) in the dose-expansion phase, and for patients who previously received crizotinib as the only ALK TKI, the ORR were 38.1% (8 of 21) and 45.7% (21 of 46) for the two phases, respectively.	Crizotinib	206-216	ALK receptor tyrosine kinase	Homo sapiens	22-25
35087031-11	2022	For patients who were ALK-rearranged and ALK TKI naive, the ORR were 81.0% (17 of 21) in the dose-escalation phase and 76.3% (29 of 38) in the dose-expansion phase, and for patients who previously received crizotinib as the only ALK TKI, the ORR were 38.1% (8 of 21) and 45.7% (21 of 46) for the two phases, respectively.	Crizotinib	206-216	ALK receptor tyrosine kinase	Homo sapiens	41-44
35110965-7	2022	The comprehensive genomic sequencing after crizotinib resistance revealed additional genetic alterations such as CD274 (also known as programmed cell death ligand 1) amplification which might be associated with treatment response of the patient.	Crizotinib	43-53	CD274 molecule	Homo sapiens	113-118
34994987-18	2022	MAIN RESULTS: Eleven studies (2874 participants) met our inclusion criteria: six studies compared an ALK inhibitor (crizotinib, ceritinib, and alectinib) to chemotherapy, and five studies compared a next-generation ALK inhibitor (alectinib, brigatinib, and lorlatinib) to crizotinib.	Crizotinib	116-126	ALK receptor tyrosine kinase	Homo sapiens	101-104
35199053-9	2022	Conclusions: In conclusion, YES1 and MYC amplifications are candidates to justify a rapid acquired resistance to crizotinib entailing primary brigatinib and lorlatinib resistance.	Crizotinib	113-123	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	37-40
34994987-27	2022	Next-generation ALK inhibitor versus crizotinib Next-generation ALK inhibitors resulted in a large increase in PFS (HR 0.39, 95% CI 0.33 to 0.46, 5 RCTs, 1263 participants, high-certainty evidence), particularly in participants with baseline brain metastases.	Crizotinib	37-47	ALK receptor tyrosine kinase	Homo sapiens	64-67
34994987-29	2022	Next-generation ALK inhibitors likely increase OS (HR 0.71, 95% CI 0.56 to 0.90, 5 RCTs, 1263 participants, moderate-certainty evidence) and slightly increase ORR (RR 1.18, 95% CI 1.10 to 1.25, 5 RCTs, 1229 participants, moderate-certainty evidence) including a response in measurable brain metastases (RR 2.45, 95% CI 1.7 to 3.54, 4 RCTs, 138 participants) when compared to crizotinib.	Crizotinib	375-385	ALK receptor tyrosine kinase	Homo sapiens	16-19
33661174-4	2022	Both crizotinib and alectinib have shown significant activity in pediatric patients with refractory ALK-positive ALCL.	Crizotinib	5-15	ALK receptor tyrosine kinase	Homo sapiens	100-103
34459458-0	2022	Fifty-five months progression-free survival with crizotinib treatment in coexistence of ALK and ROS1 rearrangements in lung adenocarcinoma: an extremely rare case and review of the literature.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	88-91
34459458-0	2022	Fifty-five months progression-free survival with crizotinib treatment in coexistence of ALK and ROS1 rearrangements in lung adenocarcinoma: an extremely rare case and review of the literature.	Crizotinib	49-59	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	96-100
34459458-1	2022	We wanted to present a case with coexistence of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangements that has been in remission for a long time with crizotinib.	Crizotinib	172-182	ALK receptor tyrosine kinase	Homo sapiens	48-74
34459458-1	2022	We wanted to present a case with coexistence of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangements that has been in remission for a long time with crizotinib.	Crizotinib	172-182	ALK receptor tyrosine kinase	Homo sapiens	76-79
34459458-1	2022	We wanted to present a case with coexistence of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangements that has been in remission for a long time with crizotinib.	Crizotinib	172-182	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	85-101
34459458-1	2022	We wanted to present a case with coexistence of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangements that has been in remission for a long time with crizotinib.	Crizotinib	172-182	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	103-107
32918045-0	2021	SAF-189s, a potent new-generation ROS1 inhibitor, is active against crizotinib-resistant ROS1 mutant-driven tumors.	Crizotinib	68-78	FAS antisense RNA 1	Homo sapiens	0-3
33887553-0	2021	Downregulation of PDGFRss Signaling Overcomes Crizotinib Resistance in a TYRO3 and ALK Mutated Neuroendocrine-Like Tumor.	Crizotinib	46-56	TYRO3 protein tyrosine kinase	Homo sapiens	73-78
33887553-5	2021	We investigated the effect of crizotinib, a chemotherapeutic known to effectively target both TYRO3 and ALK mutations.	Crizotinib	30-40	TYRO3 protein tyrosine kinase	Homo sapiens	94-99
33887553-5	2021	We investigated the effect of crizotinib, a chemotherapeutic known to effectively target both TYRO3 and ALK mutations.	Crizotinib	30-40	ALK receptor tyrosine kinase	Homo sapiens	104-107
33887553-6	2021	Crizotinib effectively decreased viability, proliferation, growth, and the metastatic properties of the PDX tumor through downregulation of STAT3 signaling, but expression of PDGFRss was increased.	Crizotinib	0-10	signal transducer and activator of transcription 3	Homo sapiens	140-145
33887553-9	2021	In combination, sunitinib was able to overcome potential crizotinib-induced resistance through downregulation of ERK 1/2 activity and PDGFRss receptor expression; consequently, tumor growth was significantly decreased both in vitro and in vivo.	Crizotinib	57-67	mitogen-activated protein kinase 3	Homo sapiens	113-120
32918045-0	2021	SAF-189s, a potent new-generation ROS1 inhibitor, is active against crizotinib-resistant ROS1 mutant-driven tumors.	Crizotinib	68-78	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	34-38
32918045-0	2021	SAF-189s, a potent new-generation ROS1 inhibitor, is active against crizotinib-resistant ROS1 mutant-driven tumors.	Crizotinib	68-78	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	89-93
32918045-2	2021	Though with significant clinical efficacy, the well-known first-generation ROS1 inhibitor (ROS1i) crizotinib inevitably developed acquired resistance due to secondary point mutations in the ROS1 kinase.	Crizotinib	98-108	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	75-79
32918045-2	2021	Though with significant clinical efficacy, the well-known first-generation ROS1 inhibitor (ROS1i) crizotinib inevitably developed acquired resistance due to secondary point mutations in the ROS1 kinase.	Crizotinib	98-108	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	91-95
32918045-11	2021	Collectively, these results suggest the promising potential of SAF-189s for the treatment of patients with the ROS1 fusion G2032R mutation who relapse on crizotinib.	Crizotinib	154-164	FAS antisense RNA 1	Homo sapiens	63-66
32918045-11	2021	Collectively, these results suggest the promising potential of SAF-189s for the treatment of patients with the ROS1 fusion G2032R mutation who relapse on crizotinib.	Crizotinib	154-164	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	111-115
34058070-9	2021	Finally, a c-MYC gain, along with a loss of CCND1 and FGFR3, were detected in a patient progressing on a first-line treatment with crizotinib.	Crizotinib	131-141	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	11-16
33784820-2	2021	We aimed to explore the potential of German claims data in this regard, exemplified by the ALK inhibitor crizotinib, used in non-small-cell lung cancer therapy.	Crizotinib	105-115	ALK receptor tyrosine kinase	Homo sapiens	91-94
33676017-0	2021	Crizotinib in Patients With MET-Amplified NSCLC.	Crizotinib	0-10	SAFB like transcription modulator	Homo sapiens	28-31
33676017-2	2021	METHODS: The influence of MET amplification on the clinical activity of the ALK/ROS1/MET inhibitor, crizotinib (250 mg twice daily), was examined in patients with NSCLC (NCT00585195) who were enrolled into high (>=4 MET-to-CEP7 ratio), medium (>2.2 to <4 MET-to-CEP7 ratio), or low (>=1.8 to <=2.2 MET-to-CEP7 ratio) amplification categories.	Crizotinib	100-110	SAFB like transcription modulator	Homo sapiens	0-3
33676017-2	2021	METHODS: The influence of MET amplification on the clinical activity of the ALK/ROS1/MET inhibitor, crizotinib (250 mg twice daily), was examined in patients with NSCLC (NCT00585195) who were enrolled into high (>=4 MET-to-CEP7 ratio), medium (>2.2 to <4 MET-to-CEP7 ratio), or low (>=1.8 to <=2.2 MET-to-CEP7 ratio) amplification categories.	Crizotinib	100-110	ALK receptor tyrosine kinase	Homo sapiens	76-79
33676017-2	2021	METHODS: The influence of MET amplification on the clinical activity of the ALK/ROS1/MET inhibitor, crizotinib (250 mg twice daily), was examined in patients with NSCLC (NCT00585195) who were enrolled into high (>=4 MET-to-CEP7 ratio), medium (>2.2 to <4 MET-to-CEP7 ratio), or low (>=1.8 to <=2.2 MET-to-CEP7 ratio) amplification categories.	Crizotinib	100-110	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	80-84
33676017-2	2021	METHODS: The influence of MET amplification on the clinical activity of the ALK/ROS1/MET inhibitor, crizotinib (250 mg twice daily), was examined in patients with NSCLC (NCT00585195) who were enrolled into high (>=4 MET-to-CEP7 ratio), medium (>2.2 to <4 MET-to-CEP7 ratio), or low (>=1.8 to <=2.2 MET-to-CEP7 ratio) amplification categories.	Crizotinib	100-110	SAFB like transcription modulator	Homo sapiens	26-29
33676017-2	2021	METHODS: The influence of MET amplification on the clinical activity of the ALK/ROS1/MET inhibitor, crizotinib (250 mg twice daily), was examined in patients with NSCLC (NCT00585195) who were enrolled into high (>=4 MET-to-CEP7 ratio), medium (>2.2 to <4 MET-to-CEP7 ratio), or low (>=1.8 to <=2.2 MET-to-CEP7 ratio) amplification categories.	Crizotinib	100-110	SAFB like transcription modulator	Homo sapiens	26-29
33676017-2	2021	METHODS: The influence of MET amplification on the clinical activity of the ALK/ROS1/MET inhibitor, crizotinib (250 mg twice daily), was examined in patients with NSCLC (NCT00585195) who were enrolled into high (>=4 MET-to-CEP7 ratio), medium (>2.2 to <4 MET-to-CEP7 ratio), or low (>=1.8 to <=2.2 MET-to-CEP7 ratio) amplification categories.	Crizotinib	100-110	SAFB like transcription modulator	Homo sapiens	26-29
33676017-2	2021	METHODS: The influence of MET amplification on the clinical activity of the ALK/ROS1/MET inhibitor, crizotinib (250 mg twice daily), was examined in patients with NSCLC (NCT00585195) who were enrolled into high (>=4 MET-to-CEP7 ratio), medium (>2.2 to <4 MET-to-CEP7 ratio), or low (>=1.8 to <=2.2 MET-to-CEP7 ratio) amplification categories.	Crizotinib	100-110	SAFB like transcription modulator	Homo sapiens	26-29
33676017-11	2021	CONCLUSIONS: Patients with high-level, MET-amplified NSCLC responded to crizotinib with the highest ORR.	Crizotinib	72-82	SAFB like transcription modulator	Homo sapiens	39-42
33676017-12	2021	Use of combined diagnostics for MET and other oncogenes may potentially identify patients most likely to respond to crizotinib.	Crizotinib	116-126	SAFB like transcription modulator	Homo sapiens	32-35
33939293-5	2021	Although crizotinib was administered due to the positivity for ALK fusion, brain metastases appeared at 19.0 months after the start of treatment.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	63-66
34058070-9	2021	Finally, a c-MYC gain, along with a loss of CCND1 and FGFR3, were detected in a patient progressing on a first-line treatment with crizotinib.	Crizotinib	131-141	cyclin D1	Homo sapiens	44-49
34058070-9	2021	Finally, a c-MYC gain, along with a loss of CCND1 and FGFR3, were detected in a patient progressing on a first-line treatment with crizotinib.	Crizotinib	131-141	fibroblast growth factor receptor 3	Homo sapiens	54-59
33685866-14	2021	CONCLUSIONS: ROS1 mutations mediate resistance to crizotinib and lorlatinib in over one-third of cases, underscoring the importance of developing next-generation ROS1 inhibitors with potency against these mutations including G2032R and L2086F.	Crizotinib	50-60	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	13-17
34051652-1	2021	BACKGROUND: The next-generation ALK inhibitor brigatinib is approved for use in patients with ALK inhibitor-naive ALK-positive advanced NSCLC and in patients previously treated with crizotinib.	Crizotinib	182-192	ALK receptor tyrosine kinase	Homo sapiens	32-35
33685866-0	2021	Spectrum of Mechanisms of Resistance to Crizotinib and Lorlatinib in ROS1 Fusion-Positive Lung Cancer.	Crizotinib	40-50	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	69-73
33685866-14	2021	CONCLUSIONS: ROS1 mutations mediate resistance to crizotinib and lorlatinib in over one-third of cases, underscoring the importance of developing next-generation ROS1 inhibitors with potency against these mutations including G2032R and L2086F.	Crizotinib	50-60	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	162-166
33685866-1	2021	PURPOSE: Current standard initial therapy for advanced, ROS1 fusion-positive (ROS1+) non-small cell lung cancer (NSCLC) is crizotinib or entrectinib.	Crizotinib	123-133	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	56-60
33905667-2	2021	Brigatinib was first used to treat Crizotinib-resistant patients because it can target resistance mutations in ALK fusion protein.	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	111-114
33685866-1	2021	PURPOSE: Current standard initial therapy for advanced, ROS1 fusion-positive (ROS1+) non-small cell lung cancer (NSCLC) is crizotinib or entrectinib.	Crizotinib	123-133	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	78-82
33991153-0	2021	Response to crizotinib in a patient with MET-amplified hepatocellular carcinoma.	Crizotinib	12-22	SAFB like transcription modulator	Homo sapiens	41-44
34004505-0	2021	Crizotinib resistance: BRAF mutation implications for therapeutic strategies.	Crizotinib	0-10	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	23-27
33960639-4	2021	Here, we report a rare case of striatin (STRN)-ALK-positive NSCLC showing primary resistance to first-line therapy alectinib and limited clinical activity of crizotinib in the alectinib-resistant setting.	Crizotinib	158-168	striatin	Homo sapiens	31-39
34055614-4	2021	Case Presentation: We report a case of a 62-year-old man diagnosed with ROS1-rearranged metastatic lung adenocarcinoma, who received first-line treatment with crizotinib for 19 months.	Crizotinib	159-169	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	72-76
33960745-7	2021	METHODS AND RESULTS: We retrospectively analyzed the radiographic and clinical characteristics of CNS progression in ALK-positive NSCLC patients treated with crizotinib or alectinib at our hospital between July 2011 and May 2020.	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	117-120
33994796-0	2021	A Phase I Trial of the MET/ALK/ROS1 Inhibitor Crizotinib Combined with the VEGF Inhibitor Pazopanib in Patients with Advanced Solid Malignancies.	Crizotinib	46-56	SAFB like transcription modulator	Homo sapiens	23-26
33994796-0	2021	A Phase I Trial of the MET/ALK/ROS1 Inhibitor Crizotinib Combined with the VEGF Inhibitor Pazopanib in Patients with Advanced Solid Malignancies.	Crizotinib	46-56	ALK receptor tyrosine kinase	Homo sapiens	27-30
33994796-0	2021	A Phase I Trial of the MET/ALK/ROS1 Inhibitor Crizotinib Combined with the VEGF Inhibitor Pazopanib in Patients with Advanced Solid Malignancies.	Crizotinib	46-56	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	31-35
33994796-1	2021	Background: Crizotinib inhibits ALK, MET and ROS1 tyrosine kinases but the development of resistance to monotherapy is an issue.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	32-35
33960639-4	2021	Here, we report a rare case of striatin (STRN)-ALK-positive NSCLC showing primary resistance to first-line therapy alectinib and limited clinical activity of crizotinib in the alectinib-resistant setting.	Crizotinib	158-168	striatin	Homo sapiens	41-45
33994796-1	2021	Background: Crizotinib inhibits ALK, MET and ROS1 tyrosine kinases but the development of resistance to monotherapy is an issue.	Crizotinib	12-22	SAFB like transcription modulator	Homo sapiens	37-40
33960639-4	2021	Here, we report a rare case of striatin (STRN)-ALK-positive NSCLC showing primary resistance to first-line therapy alectinib and limited clinical activity of crizotinib in the alectinib-resistant setting.	Crizotinib	158-168	ALK receptor tyrosine kinase	Homo sapiens	47-50
33994796-1	2021	Background: Crizotinib inhibits ALK, MET and ROS1 tyrosine kinases but the development of resistance to monotherapy is an issue.	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	45-49
33545388-14	2021	MET D1228 and Y1230 mutations and MAPK alterations were recurrently detected in post-crizotinib, pre-capmatinib plasma.	Crizotinib	85-95	SAFB like transcription modulator	Homo sapiens	0-3
34036223-2	2021	However, there is limited evidence on the clinical response to ALK tyrosine kinase inhibitors (TKIs), such as alectinib and crizotinib, in rare tumors with ALK fusion.	Crizotinib	124-134	ALK receptor tyrosine kinase	Homo sapiens	63-66
34036223-2	2021	However, there is limited evidence on the clinical response to ALK tyrosine kinase inhibitors (TKIs), such as alectinib and crizotinib, in rare tumors with ALK fusion.	Crizotinib	124-134	ALK receptor tyrosine kinase	Homo sapiens	156-159
34036227-0	2021	Clinical Responses to Crizotinib, Alectinib, and Lorlatinib in a Metastatic Colorectal Carcinoma Patient With ALK Gene Rearrangement: A Case Report.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	110-113
33164142-9	2021	Sufficient ligand-dependent MET signalling activation increased the sensitivity to crizotinib.	Crizotinib	83-93	SAFB like transcription modulator	Homo sapiens	28-31
33423957-5	2021	The correlation between ALK, ROS-1, c-MET, and other common driver gene abnormalities and the therapeutic response to crizotinib in ALK-positive patients were also evaluated.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	132-135
33423957-7	2021	Twenty-two of the 31 ALK-positive patients were treated with crizotinib at our institution (2 were lost to follow-up), and the overall response rate was 75.0 % (15 of 20); disease control rate was 90.0% (18 of 20).	Crizotinib	61-71	ALK receptor tyrosine kinase	Homo sapiens	21-24
33545388-16	2021	CONCLUSION: Capmatinib has modest activity in crizotinib-pretreated MET-altered NSCLC, potentially due to overlapping resistance mechanisms.	Crizotinib	46-56	SAFB like transcription modulator	Homo sapiens	68-71
33676682-5	2021	Herein, we developed a new small molecular fluorescence probe, namely Crizotinib-PEG4-MPA, specifically binds to c-Met in CRC cells and colitis-associated cancer adenoma.	Crizotinib	70-80	small nuclear ribonucleoprotein N	Mus musculus	81-85
33676682-5	2021	Herein, we developed a new small molecular fluorescence probe, namely Crizotinib-PEG4-MPA, specifically binds to c-Met in CRC cells and colitis-associated cancer adenoma.	Crizotinib	70-80	met proto-oncogene	Mus musculus	113-118
33676682-6	2021	In vitro binding studies confirmed the specificity and selectively of Crizotinib-PEG4-MPA against c-Met, the corresponding apparent equilibrium dissociation constants (Kd) was 3.86 muM for Crizotinib-PEG4-MPA.	Crizotinib	70-80	small nuclear ribonucleoprotein N	Mus musculus	81-85
33676682-6	2021	In vitro binding studies confirmed the specificity and selectively of Crizotinib-PEG4-MPA against c-Met, the corresponding apparent equilibrium dissociation constants (Kd) was 3.86 muM for Crizotinib-PEG4-MPA.	Crizotinib	70-80	met proto-oncogene	Mus musculus	98-103
33847874-0	2021	The Activity of Crizotinib in Chemo-Refractory MET-Amplified Esophageal and Gastric Adenocarcinomas: Results from the AcSe-Crizotinib Program.	Crizotinib	16-26	SAFB like transcription modulator	Homo sapiens	47-50
33847874-3	2021	OBJECTIVE: The objective of the study was to evaluate the efficacy and tolerability of crizotinib in patients with pretreated esogastric MET-amplified adenocarcinoma who have no alternative treatment options.	Crizotinib	87-97	SAFB like transcription modulator	Homo sapiens	137-140
33676682-6	2021	In vitro binding studies confirmed the specificity and selectively of Crizotinib-PEG4-MPA against c-Met, the corresponding apparent equilibrium dissociation constants (Kd) was 3.86 muM for Crizotinib-PEG4-MPA.	Crizotinib	70-80	small nuclear ribonucleoprotein N	Mus musculus	200-204
33676682-6	2021	In vitro binding studies confirmed the specificity and selectively of Crizotinib-PEG4-MPA against c-Met, the corresponding apparent equilibrium dissociation constants (Kd) was 3.86 muM for Crizotinib-PEG4-MPA.	Crizotinib	189-199	small nuclear ribonucleoprotein N	Mus musculus	81-85
33676682-6	2021	In vitro binding studies confirmed the specificity and selectively of Crizotinib-PEG4-MPA against c-Met, the corresponding apparent equilibrium dissociation constants (Kd) was 3.86 muM for Crizotinib-PEG4-MPA.	Crizotinib	189-199	met proto-oncogene	Mus musculus	98-103
33676682-6	2021	In vitro binding studies confirmed the specificity and selectively of Crizotinib-PEG4-MPA against c-Met, the corresponding apparent equilibrium dissociation constants (Kd) was 3.86 muM for Crizotinib-PEG4-MPA.	Crizotinib	189-199	small nuclear ribonucleoprotein N	Mus musculus	200-204
34059475-0	2021	Early Alectinib Resistance From MET Amplification in ALK-Rearranged NSCLC: Response to Crizotinib with Re-Response to Alectinib and Crizotinib.	Crizotinib	87-97	SAFB like transcription modulator	Homo sapiens	32-35
34059475-0	2021	Early Alectinib Resistance From MET Amplification in ALK-Rearranged NSCLC: Response to Crizotinib with Re-Response to Alectinib and Crizotinib.	Crizotinib	87-97	ALK receptor tyrosine kinase	Homo sapiens	53-56
34059475-0	2021	Early Alectinib Resistance From MET Amplification in ALK-Rearranged NSCLC: Response to Crizotinib with Re-Response to Alectinib and Crizotinib.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	53-56
33844110-9	2021	One novel EML4-ALK variant was also encountered which was found to be intrinsically resistant to crizotinib.	Crizotinib	97-107	EMAP like 4	Homo sapiens	10-14
33847688-5	2021	She was successfully treated with an ALK inhibitor, crizotinib.	Crizotinib	52-62	ALK receptor tyrosine kinase	Homo sapiens	37-40
33849345-0	2021	Crizotinib for c-MET-amplified advanced NSCLC: a single-center experience.	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	15-20
33849345-4	2021	METHODS: In our study, data of patients with c-MET amplification who received crizotinib treatment between July 2017 and November 2020 in the Medical Oncology Clinic of Bakirkoy Dr. Sadi Konuk Training and Research Hospital were retrospectively analyzed.	Crizotinib	78-88	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	45-50
33849345-6	2021	RESULTS: Eight of 28 patients who received crizotinib treatment had c-MET amplification.	Crizotinib	43-53	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	68-73
33919702-8	2021	Kinase activity profiling showed an association of crizotinib resistance with compensatory PI3K/AKT and MAP kinase signaling.	Crizotinib	51-61	AKT serine/threonine kinase 1	Homo sapiens	96-99
33844110-9	2021	One novel EML4-ALK variant was also encountered which was found to be intrinsically resistant to crizotinib.	Crizotinib	97-107	ALK receptor tyrosine kinase	Homo sapiens	15-18
33040544-1	2021	Crizotinib is the first-line drug for non-small cell lung cancer (NSCLC) patients who display anaplastic lymphoma kinase (ALK) rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	94-120
33917039-2	2021	The ROS-1 inhibitor, crizotinib, demonstrated resistance due to the Gly2032Arg mutation.	Crizotinib	21-31	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	4-9
33040544-1	2021	Crizotinib is the first-line drug for non-small cell lung cancer (NSCLC) patients who display anaplastic lymphoma kinase (ALK) rearrangement.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	122-125
33040544-2	2021	With 60% overall response rate, crizotinib significantly prolongs median progression-free survival (ranged 8-10 months) of ALK rearrangement NSCLC patients.	Crizotinib	32-42	ALK receptor tyrosine kinase	Homo sapiens	123-126
33040544-4	2021	Here, we describe a 47 years old woman with ALK-rearranged NSCLC who developed interstitial pneumonia (IP) induced by crizotinib.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	44-47
33196586-27	2021	Moreover, in an in vivo assay, crizotinib, a ROS1 inhibitor, markedly inhibited the growth of MAN1A1-ROS1 rearrangement-induced transformed cells in a dose-dependent manner.	Crizotinib	31-41	Ros1 proto-oncogene	Mus musculus	45-49
33196586-27	2021	Moreover, in an in vivo assay, crizotinib, a ROS1 inhibitor, markedly inhibited the growth of MAN1A1-ROS1 rearrangement-induced transformed cells in a dose-dependent manner.	Crizotinib	31-41	mannosidase 1, alpha	Mus musculus	94-100
33196586-27	2021	Moreover, in an in vivo assay, crizotinib, a ROS1 inhibitor, markedly inhibited the growth of MAN1A1-ROS1 rearrangement-induced transformed cells in a dose-dependent manner.	Crizotinib	31-41	Ros1 proto-oncogene	Mus musculus	101-105
33497758-2	2021	Agents targeting MET and its ligand hepatocyte growth factor (HGF) including small molecules such as crizotinib, tivantinib and cabozantinib or antibodies including rilotumumab and onartuzumab have proven their values in different tumors.	Crizotinib	101-111	SAFB like transcription modulator	Homo sapiens	17-20
33497758-2	2021	Agents targeting MET and its ligand hepatocyte growth factor (HGF) including small molecules such as crizotinib, tivantinib and cabozantinib or antibodies including rilotumumab and onartuzumab have proven their values in different tumors.	Crizotinib	101-111	hepatocyte growth factor	Homo sapiens	36-60
33497758-2	2021	Agents targeting MET and its ligand hepatocyte growth factor (HGF) including small molecules such as crizotinib, tivantinib and cabozantinib or antibodies including rilotumumab and onartuzumab have proven their values in different tumors.	Crizotinib	101-111	hepatocyte growth factor	Homo sapiens	62-65
33912240-3	2021	Crizotinib and ceritinib are two ALK inhibitors which are available and have been used in IMTs; however, ceritinib is much more affordable in the low- and middle-income country (LMIC) setting than crizotinib.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	33-36
33637344-0	2021	Coexistence of a novel RGS18 downstream intergenic region ALK fusion and a THUMPD2-ALK fusion in a lung adenocarcinoma patient and response to crizotinib.	Crizotinib	143-153	regulator of G protein signaling 18	Homo sapiens	23-28
33637344-0	2021	Coexistence of a novel RGS18 downstream intergenic region ALK fusion and a THUMPD2-ALK fusion in a lung adenocarcinoma patient and response to crizotinib.	Crizotinib	143-153	ALK receptor tyrosine kinase	Homo sapiens	58-61
33637344-0	2021	Coexistence of a novel RGS18 downstream intergenic region ALK fusion and a THUMPD2-ALK fusion in a lung adenocarcinoma patient and response to crizotinib.	Crizotinib	143-153	THUMP domain containing 2	Homo sapiens	75-82
33637344-0	2021	Coexistence of a novel RGS18 downstream intergenic region ALK fusion and a THUMPD2-ALK fusion in a lung adenocarcinoma patient and response to crizotinib.	Crizotinib	143-153	ALK receptor tyrosine kinase	Homo sapiens	83-86
33667719-15	2021	Patients with MET exon 14 skipping alteration demonstrate disease control with crizotinib, platinum-based chemotherapy and immunotherapy.	Crizotinib	79-89	SAFB like transcription modulator	Homo sapiens	14-17
33530027-8	2021	Based on genomic data and associated functional validation, the patient was treated with the ALK inhibitor crizotinib in combination with conventional chemotherapy (cisplatin and gemcitabine).	Crizotinib	107-117	ALK receptor tyrosine kinase	Homo sapiens	93-96
33091968-4	2021	The patient was therefore given an endobronchial cryotherapy and ALK inhibitor crizotinib.	Crizotinib	79-89	ALK receptor tyrosine kinase	Homo sapiens	65-68
33896729-0	2021	A Case of Small Cell Lung Carcinoma Harboring an EML4-ALK Fusion with Partial Response to Crizotinib.	Crizotinib	90-100	EMAP like 4	Homo sapiens	49-53
33896729-0	2021	A Case of Small Cell Lung Carcinoma Harboring an EML4-ALK Fusion with Partial Response to Crizotinib.	Crizotinib	90-100	ALK receptor tyrosine kinase	Homo sapiens	54-57
33976623-0	2021	Combination of Crizotinib and Osimertinib in T790M+ EGFR-Mutant Non-Small Cell Lung Cancer with Emerging MET Amplification Post-Osimertinib Progression in a 10-Year Survivor: A Case Report.	Crizotinib	15-25	SAFB like transcription modulator	Homo sapiens	105-108
33832282-0	2021	A rare KIF5B-ALK fusion variant in a lung adenocarcinoma patient who responded to crizotinib and acquired the ALK L1196M mutation after resistance: a case report.	Crizotinib	82-92	ALK receptor tyrosine kinase	Homo sapiens	13-16
33832282-7	2021	As far as we know, this is the first report showing that KIF5B-ALK (K20:A20) is a fusion variant that is sensitive to crizotinib.	Crizotinib	118-128	kinesin family member 5B	Homo sapiens	57-62
33832282-7	2021	As far as we know, this is the first report showing that KIF5B-ALK (K20:A20) is a fusion variant that is sensitive to crizotinib.	Crizotinib	118-128	ALK receptor tyrosine kinase	Homo sapiens	63-66
33832282-7	2021	As far as we know, this is the first report showing that KIF5B-ALK (K20:A20) is a fusion variant that is sensitive to crizotinib.	Crizotinib	118-128	immunoglobulin kappa variable 1-27	Homo sapiens	72-75
33832282-8	2021	We provided a treatment strategy for managing NSCLC patients with KIF5B-ALK (K20:A20) fusion or ALK L1196M mutation after crizotinib resistance.	Crizotinib	122-132	kinesin family member 5B	Homo sapiens	66-71
33832282-8	2021	We provided a treatment strategy for managing NSCLC patients with KIF5B-ALK (K20:A20) fusion or ALK L1196M mutation after crizotinib resistance.	Crizotinib	122-132	ALK receptor tyrosine kinase	Homo sapiens	96-99
33976623-3	2021	This report describes the successful results obtained with the combination of the third-generation TKI osimertinib with the multitargeted TKI and MET inhibitor crizotinib in a patient with EGFR-mutant NSCLC with emerging MET amplification with a tolerable toxicity profile.	Crizotinib	160-170	SAFB like transcription modulator	Homo sapiens	146-149
33976623-3	2021	This report describes the successful results obtained with the combination of the third-generation TKI osimertinib with the multitargeted TKI and MET inhibitor crizotinib in a patient with EGFR-mutant NSCLC with emerging MET amplification with a tolerable toxicity profile.	Crizotinib	160-170	epidermal growth factor receptor	Homo sapiens	189-193
33976623-3	2021	This report describes the successful results obtained with the combination of the third-generation TKI osimertinib with the multitargeted TKI and MET inhibitor crizotinib in a patient with EGFR-mutant NSCLC with emerging MET amplification with a tolerable toxicity profile.	Crizotinib	160-170	SAFB like transcription modulator	Homo sapiens	221-224
33841676-0	2021	Efficacy and safety of crizotinib plus bevacizumab in ALK/ROS-1/c-MET positive non-small cell lung cancer: an open-label, single-arm, prospective observational study.	Crizotinib	23-33	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	58-63
33841676-0	2021	Efficacy and safety of crizotinib plus bevacizumab in ALK/ROS-1/c-MET positive non-small cell lung cancer: an open-label, single-arm, prospective observational study.	Crizotinib	23-33	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	64-69
33841676-1	2021	BACKGROUND: Crizotinib is a tyrosine kinase inhibitor (TKI) effective in ALK/ROS-1/c-MET positive non-small cell lung cancer (NSCLC) patients.	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	73-76
33841676-1	2021	BACKGROUND: Crizotinib is a tyrosine kinase inhibitor (TKI) effective in ALK/ROS-1/c-MET positive non-small cell lung cancer (NSCLC) patients.	Crizotinib	12-22	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	77-82
33841676-1	2021	BACKGROUND: Crizotinib is a tyrosine kinase inhibitor (TKI) effective in ALK/ROS-1/c-MET positive non-small cell lung cancer (NSCLC) patients.	Crizotinib	12-22	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	83-88
33841676-3	2021	However, the efficacy and safety of crizotinib plus bevacizumab in treating naive ALK/ROS-1/c-MET positive NSCLC patients have not been studied.	Crizotinib	36-46	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	86-93
33841676-4	2021	METHODS: In this open-label, single-arm, prospective observational study, locally advanced or metastatic ALK rearrangement/ROS-1 fusion/c-MET amplification NSCLC patients were treated with crizotinib (250 mg orally twice daily) and bevacizumab (7.5 mg/kg intravenous every three weeks) until disease progression or intolerant toxicity or death.	Crizotinib	189-199	ALK receptor tyrosine kinase	Homo sapiens	105-108
33841676-4	2021	METHODS: In this open-label, single-arm, prospective observational study, locally advanced or metastatic ALK rearrangement/ROS-1 fusion/c-MET amplification NSCLC patients were treated with crizotinib (250 mg orally twice daily) and bevacizumab (7.5 mg/kg intravenous every three weeks) until disease progression or intolerant toxicity or death.	Crizotinib	189-199	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	123-128
33841676-4	2021	METHODS: In this open-label, single-arm, prospective observational study, locally advanced or metastatic ALK rearrangement/ROS-1 fusion/c-MET amplification NSCLC patients were treated with crizotinib (250 mg orally twice daily) and bevacizumab (7.5 mg/kg intravenous every three weeks) until disease progression or intolerant toxicity or death.	Crizotinib	189-199	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	136-141
33841676-16	2021	INTERPRETATION: This study demonstrated that crizotinib plus bevacizumab showed benefit in treating naive ALK rearrangement NSCLC patients, and the toxicity was relatively tolerant.	Crizotinib	45-55	ALK receptor tyrosine kinase	Homo sapiens	106-109
33841676-17	2021	Our results suggested that crizotinib plus bevacizumab might be a promising treatment strategy in ALK/ROS-1/c-MET positive NSCLC patients.	Crizotinib	27-37	ALK receptor tyrosine kinase	Homo sapiens	98-101
33841676-17	2021	Our results suggested that crizotinib plus bevacizumab might be a promising treatment strategy in ALK/ROS-1/c-MET positive NSCLC patients.	Crizotinib	27-37	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	102-109
33712615-7	2021	In combination with EGFR inhibitors, crizotinib inhibits the emergence of a defined subset of EGFR inhibitor-tolerant clones.	Crizotinib	37-47	epidermal growth factor receptor	Homo sapiens	20-24
33712615-7	2021	In combination with EGFR inhibitors, crizotinib inhibits the emergence of a defined subset of EGFR inhibitor-tolerant clones.	Crizotinib	37-47	epidermal growth factor receptor	Homo sapiens	94-98
33682977-0	2021	Novel SLC12A2-ROS1 fusion in non-small-cell lung cancer with a significant response to crizotinib: the importance of choosing the appropriate next-generation sequencing assay.	Crizotinib	87-97	solute carrier family 12 member 2	Homo sapiens	6-13
33682977-0	2021	Novel SLC12A2-ROS1 fusion in non-small-cell lung cancer with a significant response to crizotinib: the importance of choosing the appropriate next-generation sequencing assay.	Crizotinib	87-97	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	14-18
33682977-3	2021	We describe a novel SLC12A2-ROS1 rearrangement that has not been previously reported in other cancers, a fusion that has clinical and radiological sensitivity to crizotinib.	Crizotinib	162-172	solute carrier family 12 member 2	Homo sapiens	20-27
33682977-3	2021	We describe a novel SLC12A2-ROS1 rearrangement that has not been previously reported in other cancers, a fusion that has clinical and radiological sensitivity to crizotinib.	Crizotinib	162-172	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	28-32
33682977-7	2021	Given our patient"s response to crizotinib, identifying patients with undescribed ROS1 fusions has important therapeutic implications.	Crizotinib	32-42	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	82-86
33021405-7	2021	In two animal models with established PAH (i.e. monocrotaline and Sugen/hypoxia-treated rats), pharmacological inhibition of NUDT1 using (S)-Crizotinib significantly decreased pulmonary vascular remodeling and improved hemodynamics and cardiac function.	Crizotinib	137-151	nudix hydrolase 1	Rattus norvegicus	125-130
33538211-0	2021	Targeting MET amplification with crizotinib in a case of sinonasal undifferentiated carcinoma.	Crizotinib	33-43	SAFB like transcription modulator	Homo sapiens	10-13
33538211-4	2021	The patient was treated with crizotinib, a tyrosine kinase inhibitor that targets c-MET, and experienced a complete response.	Crizotinib	29-39	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	82-87
33222380-0	2021	Pharmacoenhancement of Low Crizotinib Plasma Concentrations in Patients with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer using the CYP3A Inhibitor Cobicistat.	Crizotinib	27-37	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	150-155
33222380-1	2021	The inhibitor of anaplastic lymphoma kinase (ALK) crizotinib significantly increases survival in patients with ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	17-43
33222380-1	2021	The inhibitor of anaplastic lymphoma kinase (ALK) crizotinib significantly increases survival in patients with ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	45-48
33222380-1	2021	The inhibitor of anaplastic lymphoma kinase (ALK) crizotinib significantly increases survival in patients with ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	50-60	ALK receptor tyrosine kinase	Homo sapiens	111-114
33222380-3	2021	We investigated whether the CYP3A inhibitor cobicistat increases Cmin,ss of the CYP3A substrate crizotinib in patients with low exposure.	Crizotinib	96-106	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	28-33
33222380-3	2021	We investigated whether the CYP3A inhibitor cobicistat increases Cmin,ss of the CYP3A substrate crizotinib in patients with low exposure.	Crizotinib	96-106	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	80-85
33222380-4	2021	Patients with ALK-positive NSCLC of our outpatient clinic treated with crizotinib were enrolled in a phase I trial (EudraCT 2016-002187-14, DRKS00012360) if crizotinib Cmin,ss was below 310 ng/mL and treated with cobicistat for 14 days.	Crizotinib	71-81	ALK receptor tyrosine kinase	Homo sapiens	14-17
33486442-0	2021	Sequential therapy of crizotinib followed by alectinib for non-small cell lung cancer harbouring anaplastic lymphoma kinase rearrangement (WJOG9516L): A multicenter retrospective cohort study.	Crizotinib	22-32	ALK receptor tyrosine kinase	Homo sapiens	97-123
33486442-2	2021	METHODS: We reviewed the clinical data of patients with ALK-rearranged non-small cell lung cancer who received crizotinib (CRZ) or alectinib (ALEC) between May 2012 and December 2016.	Crizotinib	111-121	ALK receptor tyrosine kinase	Homo sapiens	56-59
33486442-2	2021	METHODS: We reviewed the clinical data of patients with ALK-rearranged non-small cell lung cancer who received crizotinib (CRZ) or alectinib (ALEC) between May 2012 and December 2016.	Crizotinib	123-126	ALK receptor tyrosine kinase	Homo sapiens	56-59
33387041-0	2021	Impact of STAT1 polymorphisms on crizotinib-induced hepatotoxicity in ALK-positive non-small cell lung cancer patients.	Crizotinib	33-43	signal transducer and activator of transcription 1	Homo sapiens	10-15
33387041-0	2021	Impact of STAT1 polymorphisms on crizotinib-induced hepatotoxicity in ALK-positive non-small cell lung cancer patients.	Crizotinib	33-43	ALK receptor tyrosine kinase	Homo sapiens	70-73
33387041-1	2021	PURPOSE: Crizotinib is the first-line small molecule tyrosine kinase inhibitor for ALK-positive non-small cell lung cancer.	Crizotinib	9-19	ALK receptor tyrosine kinase	Homo sapiens	83-86
33387041-2	2021	In this study, a retrospective pharmacogenomics investigation was conducted to explore the relationship between genes related to RTK downstream signaling pathways and crizotinib-induced hepatic toxicity in ALK-positive NSCLC patients.	Crizotinib	167-177	ALK receptor tyrosine kinase	Homo sapiens	206-209
33387041-12	2021	In multiple logistic regression, STAT1 rs10208033 (T > C) was significantly associated with crizotinib-induced liver toxicity (OR = 6.733, 95% CI 1.406-32.24, P = 0.017).	Crizotinib	92-102	signal transducer and activator of transcription 1	Homo sapiens	33-38
33387041-13	2021	Compared with non-CC, OR is 5.5 (95% CI 1.219-24.81, P = 0.027) for STAT1 rs10208033 CC genotype to develop crizotinib-induced liver toxicity.	Crizotinib	108-118	signal transducer and activator of transcription 1	Homo sapiens	68-73
33387041-14	2021	Further cell viability test in human fetal hepatocyte line, L-02, reveals that the STAT1 inhibitor might protect hepatocyte cells from the toxicity caused by crizotinib.	Crizotinib	158-168	signal transducer and activator of transcription 1	Homo sapiens	83-88
33387041-16	2021	These results suggest that STAT1 plays an important role in crizotinib-induced hepatotoxicity.	Crizotinib	60-70	signal transducer and activator of transcription 1	Homo sapiens	27-32
33248323-9	2021	Patients with uncommon ALK fusion (n=31) who received first-line crizotinib exhibited shorter median progression-free survival (PFS) than patients with canonical ALK fusion (n=53, 8.4 months versus 12.0 months; P=0.004).	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	23-26
33155495-0	2021	Combination of crizotinib and chemotherapy in patients with relapsed or refractory anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL).	Crizotinib	15-25	ALK receptor tyrosine kinase	Homo sapiens	83-109
33155495-0	2021	Combination of crizotinib and chemotherapy in patients with relapsed or refractory anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL).	Crizotinib	15-25	ALK receptor tyrosine kinase	Homo sapiens	111-114
33155495-9	2021	Thus, the combination of crizotinib with chemotherapy might be effective in ALK-positive and crizotinib sensitive r/r sALCL patients.	Crizotinib	25-35	ALK receptor tyrosine kinase	Homo sapiens	76-79
33472762-0	2021	Appearance of an ALK mutation conferring resistance to crizotinib in non-small cell lung cancer harboring oncogenic ROS1 fusion.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	17-20
33472762-0	2021	Appearance of an ALK mutation conferring resistance to crizotinib in non-small cell lung cancer harboring oncogenic ROS1 fusion.	Crizotinib	55-65	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	116-120
33000474-0	2021	Acquired MET D1228N mutations mediate crizotinib resistance in lung adenocarcinoma with ROS1 fusion: a case report.	Crizotinib	38-48	SAFB like transcription modulator	Homo sapiens	9-12
33849345-10	2021	CONCLUSION: Crizotinib is an effective treatment option other than cytotoxic chemotherapy in the limited number of patients with MET amplification in the stage 4 lung adenocarcinoma subgroup.	Crizotinib	12-22	SAFB like transcription modulator	Homo sapiens	129-132
33000474-0	2021	Acquired MET D1228N mutations mediate crizotinib resistance in lung adenocarcinoma with ROS1 fusion: a case report.	Crizotinib	38-48	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	88-92
33000474-1	2021	Patients with non-small cell lung cancer (NSCLC) containing ROS1 fusions can have a marked response to the ROS1-targeted tyrosine kinase inhibitors (TKI), such as crizotinib.	Crizotinib	163-173	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	60-64
33000474-1	2021	Patients with non-small cell lung cancer (NSCLC) containing ROS1 fusions can have a marked response to the ROS1-targeted tyrosine kinase inhibitors (TKI), such as crizotinib.	Crizotinib	163-173	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	107-111
33000474-5	2021	Here we describe a patient with metastatic lung adenocarcinoma with CD74-ROS1 fusion who initially responded to crizotinib and then developed resistance by the acquired mutation of D1228N in the MET kinase domain, which showed short-term disease control for cabozantinib.	Crizotinib	112-122	CD74 molecule	Homo sapiens	68-72
33000474-5	2021	Here we describe a patient with metastatic lung adenocarcinoma with CD74-ROS1 fusion who initially responded to crizotinib and then developed resistance by the acquired mutation of D1228N in the MET kinase domain, which showed short-term disease control for cabozantinib.	Crizotinib	112-122	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	73-77
33438350-3	2021	Crizotinib was administered in combination with osimertinib due to elevated mesenchymal epithelial transition (MET) copy number amplification.	Crizotinib	0-10	SAFB like transcription modulator	Homo sapiens	111-114
33470536-0	2021	Crizotinib for recurring non-small-cell lung cancer with EML4-ALK fusion genes previously treated with alectinib: A phase II trial.	Crizotinib	0-10	EMAP like 4	Homo sapiens	57-61
33889527-0	2021	Concomitant mutation status of ALK-rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib.	Crizotinib	125-135	ALK receptor tyrosine kinase	Homo sapiens	31-34
33470536-0	2021	Crizotinib for recurring non-small-cell lung cancer with EML4-ALK fusion genes previously treated with alectinib: A phase II trial.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	62-65
33470536-1	2021	BACKGROUND: The efficacy of crizotinib treatment for recurring EML4-ALK-positive non-small cell lung cancer (NSCLC) previously treated with alectinib is unclear.	Crizotinib	28-38	EMAP like 4	Homo sapiens	63-67
33470536-1	2021	BACKGROUND: The efficacy of crizotinib treatment for recurring EML4-ALK-positive non-small cell lung cancer (NSCLC) previously treated with alectinib is unclear.	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	68-71
33470536-2	2021	Based on our preclinical findings regarding hepatocyte growth factor/mesenchymal epithelial transition (MET) pathway activation as a potential mechanism of acquired resistance to alectinib, we conducted a phase II trial of the anaplastic lymphoma kinase/MET inhibitor, crizotinib, in patients with alectinib-refractory, EML4-ALK-positive NSCLC.	Crizotinib	269-279	SAFB like transcription modulator	Homo sapiens	104-107
33889527-16	2021	Our study also demonstrated the prognostic value of concomitant alterations in crizotinib-treated patients, which could facilitate improved stratification of ALK-rearranged NSCLC patients in the selection of candidates who could optimally benefit from therapy.	Crizotinib	79-89	ALK receptor tyrosine kinase	Homo sapiens	158-161
32882306-0	2021	Crizotinib Associated Renal Cyst Formation in a Pediatric Patient with ALK+ Epithelioid Inflammatory Myofibroblastic Sarcoma.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	71-74
33568345-0	2021	Activity of Crizotinib in Patients with ALK-aberrant Relapsed/Refractory Neuroblastoma: A Children"s Oncology Group Study (ADVL0912).	Crizotinib	12-22	ALK receptor tyrosine kinase	Homo sapiens	40-43
32882306-1	2021	Crizotinib is a first-generation tyrosine kinase inhibitor used for anaplastic lymphoma kinase (ALK) positive cancers.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	68-94
32882306-1	2021	Crizotinib is a first-generation tyrosine kinase inhibitor used for anaplastic lymphoma kinase (ALK) positive cancers.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	96-99
32882306-3	2021	We report a case of a right renal mass in a 17-year-old with ALK-positive epithelioid inflammatory myofibroblastic sarcoma treated with Crizotinib.	Crizotinib	136-146	ALK receptor tyrosine kinase	Homo sapiens	61-64
33663095-0	2021	The impact of baseline brain metastases on clinical benefits and progression patterns after first-line crizotinib in anaplastic lymphoma kinase-rearranged non-small cell lung cancer.	Crizotinib	103-113	ALK receptor tyrosine kinase	Homo sapiens	117-143
33663095-2	2021	Crizotinib prolongs the survival of patients with ALK rearrangement but lacks significant effect on brain metastasis.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	50-53
33629198-8	2021	Moreover, in vitro, c-Met inhibitors Foretinib, Crizotinib and Cabozantinib were significantly more effective against TEC-Dys than TEC-Ortho.	Crizotinib	48-58	met proto-oncogene	Mus musculus	20-25
33568345-2	2021	We assessed the activity of first generation ALK inhibitor crizotinib in patients with no known curative treatments and whose tumors harbored an activating ALK alteration.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	45-48
33568345-2	2021	We assessed the activity of first generation ALK inhibitor crizotinib in patients with no known curative treatments and whose tumors harbored an activating ALK alteration.	Crizotinib	59-69	ALK receptor tyrosine kinase	Homo sapiens	156-159
33568345-8	2021	All three patients had a somatic ALK Arg1275Gln mutation, the most common ALK hotspot mutation observed in neuroblastoma and the only mutation predicted to be sensitive to ALK inhibition with crizotinib.	Crizotinib	192-202	ALK receptor tyrosine kinase	Homo sapiens	33-36
33528638-0	2021	The effect of EML4-ALK break-apart ratio on crizotinib outcomes in non-small cell lung cancer harboring EML4-ALK rearrangement.	Crizotinib	44-54	EMAP like 4	Homo sapiens	104-108
33528638-11	2021	The intracranial progression during crizotinib treatment was significantly frequent in the pts with high ALK rearrangement (62.5-32.5%, P 0.039) DISCUSSION: In this study, we found that the high break-apart ratio can predict the extent of benefit from targeted therapy in ALK-positive NSCLC patients.	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	105-108
33528638-11	2021	The intracranial progression during crizotinib treatment was significantly frequent in the pts with high ALK rearrangement (62.5-32.5%, P 0.039) DISCUSSION: In this study, we found that the high break-apart ratio can predict the extent of benefit from targeted therapy in ALK-positive NSCLC patients.	Crizotinib	36-46	ALK receptor tyrosine kinase	Homo sapiens	272-275
32686074-0	2021	Exposure-response analyses of anaplastic lymphoma kinase inhibitors crizotinib and alectinib in non-small-cell lung cancer patients.	Crizotinib	68-78	ALK receptor tyrosine kinase	Homo sapiens	30-56
33119140-0	2021	Dose-escalation study of vemurafenib with sorafenib or crizotinib in patients with BRAF-mutated advanced cancers.	Crizotinib	55-65	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	83-87
33119140-2	2021	The authors hypothesized that combining the BRAF inhibitor vemurafenib with either the multikinase inhibitor sorafenib or the MET inhibitor crizotinib could overcome therapeutic resistance.	Crizotinib	140-150	SAFB like transcription modulator	Homo sapiens	126-129
33119140-8	2021	CONCLUSIONS: Vemurafenib combined with sorafenib or crizotinib was well tolerated with encouraging activity, including among patients who previously received treatment with BRAF, MEK, or ERK inhibitors.	Crizotinib	52-62	mitogen-activated protein kinase kinase 7	Homo sapiens	179-182
32686074-1	2021	Crizotinib and alectinib are anaplastic lymphoma kinase (ALK)-inhibitors indicated for the treatment of ALK-positive metastatic non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	29-55
32686074-1	2021	Crizotinib and alectinib are anaplastic lymphoma kinase (ALK)-inhibitors indicated for the treatment of ALK-positive metastatic non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	57-60
32686074-1	2021	Crizotinib and alectinib are anaplastic lymphoma kinase (ALK)-inhibitors indicated for the treatment of ALK-positive metastatic non-small-cell lung cancer (NSCLC).	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	104-107
32686074-4	2021	An observational study was performed, in which ALK-positive NSCLC patients were included who were treated with crizotinib or alectinib and of whom pharmacokinetic samples were collected in routine care.	Crizotinib	111-121	ALK receptor tyrosine kinase	Homo sapiens	47-50
32686074-9	2021	In a pooled analysis of all crizotinib patients (not only ALK-positive, n=79), the HR was 2.15 (95%CI 1.21-3.84, p=0.009).	Crizotinib	28-38	ALK receptor tyrosine kinase	Homo sapiens	58-61
33597889-8	2021	Furthermore, mechanistic investigations demonstrated that crizotinib and sunitinib accumulated ROS and inhibited Nrf2 signaling, and that ROS scavenger NAC and Nrf2 agonist tBHQ alleviated the extent of cell damage and the mitochondrial apoptosis during crizotinib- and sunitinib-induced hepatotoxicity in L02 cells.	Crizotinib	58-68	NFE2 like bZIP transcription factor 2	Homo sapiens	113-117
33597889-7	2021	In vivo studies further confirmed that crizotinib and sunitinib decreased mitochondrial membrane potential and activated apoptosis-associated proteins (cleaved-PARP, cleaved caspase3, cytochrome c, Bcl2 and Bax).	Crizotinib	39-49	BCL2 associated X, apoptosis regulator	Homo sapiens	207-210
33528638-0	2021	The effect of EML4-ALK break-apart ratio on crizotinib outcomes in non-small cell lung cancer harboring EML4-ALK rearrangement.	Crizotinib	44-54	EMAP like 4	Homo sapiens	14-18
33597889-8	2021	Furthermore, mechanistic investigations demonstrated that crizotinib and sunitinib accumulated ROS and inhibited Nrf2 signaling, and that ROS scavenger NAC and Nrf2 agonist tBHQ alleviated the extent of cell damage and the mitochondrial apoptosis during crizotinib- and sunitinib-induced hepatotoxicity in L02 cells.	Crizotinib	254-264	X-linked Kx blood group	Homo sapiens	152-155
33597889-8	2021	Furthermore, mechanistic investigations demonstrated that crizotinib and sunitinib accumulated ROS and inhibited Nrf2 signaling, and that ROS scavenger NAC and Nrf2 agonist tBHQ alleviated the extent of cell damage and the mitochondrial apoptosis during crizotinib- and sunitinib-induced hepatotoxicity in L02 cells.	Crizotinib	254-264	NFE2 like bZIP transcription factor 2	Homo sapiens	160-164
33597889-9	2021	Collectively, these findings indicated that NAC and tBHQ play the crucial roles in crizotinib- and sunitinib-induced mitochondrial apoptosis via the regulation of oxidative stress.	Crizotinib	83-93	X-linked Kx blood group	Homo sapiens	44-47
33419583-0	2021	Rare coexistence of three novel CDCA7-ALK, FSIP2-ALK, ALK-ERLEC1 fusions in a lung adenocarcinoma patient who responded to Crizotinib.	Crizotinib	123-133	cell division cycle associated 7	Homo sapiens	32-37
32833135-0	2021	Crizotinib induced antitumor activity and synergized with chemotherapy and hormonal drugs in breast cancer cells via downregulating MET and estrogen receptor levels.	Crizotinib	0-10	estrogen receptor 1	Homo sapiens	140-157
32833135-2	2021	Crizotinib is an oral multi-targeted tyrosine kinase inhibitor of MET, ALK, RON, and ROS1 kinases.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	71-74
32833135-2	2021	Crizotinib is an oral multi-targeted tyrosine kinase inhibitor of MET, ALK, RON, and ROS1 kinases.	Crizotinib	0-10	macrophage stimulating 1 receptor	Homo sapiens	76-79
32833135-2	2021	Crizotinib is an oral multi-targeted tyrosine kinase inhibitor of MET, ALK, RON, and ROS1 kinases.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	85-89
32833135-7	2021	Immunofluorescence and Western blotting indicated that crizotinib reduced total levels of MET and estrogen receptor (ERalpha) in BT-474 cells.	Crizotinib	55-65	estrogen receptor 1	Homo sapiens	98-115
32833135-7	2021	Immunofluorescence and Western blotting indicated that crizotinib reduced total levels of MET and estrogen receptor (ERalpha) in BT-474 cells.	Crizotinib	55-65	estrogen receptor 1	Homo sapiens	117-124
32833135-8	2021	Also, crizotinib reduced the levels of phosphorylated (active) MET and HER2 in BT-474 cells.	Crizotinib	6-16	erb-b2 receptor tyrosine kinase 2	Homo sapiens	71-75
32915420-0	2021	A novel LRRFIP1-ALK fusion in inflammatory myofibroblastic tumor of hip and response to crizotinib.	Crizotinib	88-98	LRR binding FLII interacting protein 1	Homo sapiens	8-15
32915420-0	2021	A novel LRRFIP1-ALK fusion in inflammatory myofibroblastic tumor of hip and response to crizotinib.	Crizotinib	88-98	ALK receptor tyrosine kinase	Homo sapiens	16-19
32915420-7	2021	Crizotinib, an ALK inhibitor, was effective in the treatment of this patient, indicating that ALK inhibitors may be effective for IMT with LRRFIP1-ALK fusions.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	15-18
32915420-7	2021	Crizotinib, an ALK inhibitor, was effective in the treatment of this patient, indicating that ALK inhibitors may be effective for IMT with LRRFIP1-ALK fusions.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	94-97
32915420-7	2021	Crizotinib, an ALK inhibitor, was effective in the treatment of this patient, indicating that ALK inhibitors may be effective for IMT with LRRFIP1-ALK fusions.	Crizotinib	0-10	LRR binding FLII interacting protein 1	Homo sapiens	139-146
32915420-7	2021	Crizotinib, an ALK inhibitor, was effective in the treatment of this patient, indicating that ALK inhibitors may be effective for IMT with LRRFIP1-ALK fusions.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	94-97
33386152-0	2021	Identification of a novel NPM1-ROS1 fusion in a lung adenocarcinoma and sensitive to crizotinib treatment.	Crizotinib	85-95	nucleophosmin 1	Homo sapiens	26-30
33386152-0	2021	Identification of a novel NPM1-ROS1 fusion in a lung adenocarcinoma and sensitive to crizotinib treatment.	Crizotinib	85-95	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	31-35
33419583-0	2021	Rare coexistence of three novel CDCA7-ALK, FSIP2-ALK, ALK-ERLEC1 fusions in a lung adenocarcinoma patient who responded to Crizotinib.	Crizotinib	123-133	ALK receptor tyrosine kinase	Homo sapiens	38-41
33419583-0	2021	Rare coexistence of three novel CDCA7-ALK, FSIP2-ALK, ALK-ERLEC1 fusions in a lung adenocarcinoma patient who responded to Crizotinib.	Crizotinib	123-133	fibrous sheath interacting protein 2	Homo sapiens	43-48
33419583-0	2021	Rare coexistence of three novel CDCA7-ALK, FSIP2-ALK, ALK-ERLEC1 fusions in a lung adenocarcinoma patient who responded to Crizotinib.	Crizotinib	123-133	ALK receptor tyrosine kinase	Homo sapiens	49-52
33419583-0	2021	Rare coexistence of three novel CDCA7-ALK, FSIP2-ALK, ALK-ERLEC1 fusions in a lung adenocarcinoma patient who responded to Crizotinib.	Crizotinib	123-133	ALK receptor tyrosine kinase	Homo sapiens	49-52
33419583-0	2021	Rare coexistence of three novel CDCA7-ALK, FSIP2-ALK, ALK-ERLEC1 fusions in a lung adenocarcinoma patient who responded to Crizotinib.	Crizotinib	123-133	endoplasmic reticulum lectin 1	Homo sapiens	58-64
33444901-11	2021	There were 40 ALK-rearranged NSCLC patients receiving the first-line crizotinib.	Crizotinib	69-79	ALK receptor tyrosine kinase	Homo sapiens	14-17
33530219-0	2021	Responses to crizotinib and cabozantinib in patient with lung adenocarcinoma harboring mesenchymal-epithelial transition factor exon 14 skipping mutation: A case report.	Crizotinib	13-23	SAFB like transcription modulator	Homo sapiens	87-127
33597889-0	2021	Crizotinib and Sunitinib Induce Hepatotoxicity and Mitochondrial Apoptosis in L02 Cells via ROS and Nrf2 Signaling Pathway.	Crizotinib	0-10	NFE2 like bZIP transcription factor 2	Homo sapiens	100-104
33597889-7	2021	In vivo studies further confirmed that crizotinib and sunitinib decreased mitochondrial membrane potential and activated apoptosis-associated proteins (cleaved-PARP, cleaved caspase3, cytochrome c, Bcl2 and Bax).	Crizotinib	39-49	collagen type XI alpha 2 chain	Homo sapiens	160-164
33597889-7	2021	In vivo studies further confirmed that crizotinib and sunitinib decreased mitochondrial membrane potential and activated apoptosis-associated proteins (cleaved-PARP, cleaved caspase3, cytochrome c, Bcl2 and Bax).	Crizotinib	39-49	caspase 3	Homo sapiens	174-182
33597889-7	2021	In vivo studies further confirmed that crizotinib and sunitinib decreased mitochondrial membrane potential and activated apoptosis-associated proteins (cleaved-PARP, cleaved caspase3, cytochrome c, Bcl2 and Bax).	Crizotinib	39-49	cytochrome c, somatic	Homo sapiens	184-196
33597889-7	2021	In vivo studies further confirmed that crizotinib and sunitinib decreased mitochondrial membrane potential and activated apoptosis-associated proteins (cleaved-PARP, cleaved caspase3, cytochrome c, Bcl2 and Bax).	Crizotinib	39-49	BCL2 apoptosis regulator	Homo sapiens	198-202
33530219-5	2021	In this report, we present a MET-positive case that benefited from crizotinib and cabozantinib treatment.	Crizotinib	67-77	SAFB like transcription modulator	Homo sapiens	29-32
33435596-18	2021	A new group of drugs-small-molecule tyrosine kinase inhibitors-has been developed; the first generation includes gefitinib and erlotinib and the ALK inhibitor crizotinib.	Crizotinib	159-169	ALK receptor tyrosine kinase	Homo sapiens	145-148
33433963-3	2021	By genomic profiling of the cell block material, we identified a MET exon 14 skipping mutation that indicated a lung origin and made the patient eligible for the tyrosine kinase inhibitor, crizotinib.	Crizotinib	189-199	SAFB like transcription modulator	Homo sapiens	65-68
33454089-0	2021	Patient with EGFR-mutant lung cancer harboring de novo MET amplification successfully treated with gefitinib combined with crizotinib.	Crizotinib	123-133	epidermal growth factor receptor	Homo sapiens	13-17
33454089-0	2021	Patient with EGFR-mutant lung cancer harboring de novo MET amplification successfully treated with gefitinib combined with crizotinib.	Crizotinib	123-133	SAFB like transcription modulator	Homo sapiens	55-58
33509141-0	2021	Successful treatment with alectinib after crizotinib-induced hepatitis in ALK-rearranged advanced lung cancer patient: a case report.	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	74-77
33509141-1	2021	BACKGROUND: Besides the clinical benefit of crizotinib in ALK-rearranged metastatic non-small cell lung cancer (NSCLC), concerns about its hepatotoxicity have arisen.	Crizotinib	44-54	ALK receptor tyrosine kinase	Homo sapiens	58-61
33509141-4	2021	CASE PRESENTATION: Herein, we report a case of acute hepatitis induced by crizotinib in a 32-years-old female diagnosed with metastatic NSCLC, harboring the ALK-rearrangement.	Crizotinib	74-84	ALK receptor tyrosine kinase	Homo sapiens	157-160
33494549-2	2021	Due to higher systemic and intracranial efficacy, the second-generation ALK tyrosine kinase inhibitors (TKI) alectinib and brigatinib have irrevocably displaced crizotinib as standard first-line treatment, based on the results of the ALEX and ALTA-1L trials.	Crizotinib	161-171	ALK receptor tyrosine kinase	Homo sapiens	72-75
33449292-0	2021	Combined crizotinib and endocrine drugs inhibit proliferation, migration, and colony formation of breast cancer cells via downregulation of MET and estrogen receptor.	Crizotinib	9-19	SAFB like transcription modulator	Homo sapiens	140-143
33449292-0	2021	Combined crizotinib and endocrine drugs inhibit proliferation, migration, and colony formation of breast cancer cells via downregulation of MET and estrogen receptor.	Crizotinib	9-19	estrogen receptor 1	Homo sapiens	148-165
33449292-4	2021	Crizotinib is a small-molecule tyrosine kinase inhibitor of MET.	Crizotinib	0-10	SAFB like transcription modulator	Homo sapiens	60-63
33380260-9	2021	Furthermore, we also demonstrate the sequential use of crizotinib, brigatinib, and lorlatinib in a patient with advanced ALK-rearranged lung adenocarcinoma with an overall progression-free survival of 33.3 months for the sequential ALK inhibitor regimens.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	121-124
33430343-0	2021	Crizotinib Resistance Mediated by Autophagy Is Higher in the Stem-Like Cell Subset in ALK-Positive Anaplastic Large Cell Lymphoma, and This Effect Is MYC-Dependent.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	86-89
33430343-0	2021	Crizotinib Resistance Mediated by Autophagy Is Higher in the Stem-Like Cell Subset in ALK-Positive Anaplastic Large Cell Lymphoma, and This Effect Is MYC-Dependent.	Crizotinib	0-10	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	150-153
33430343-1	2021	Previously it was shown that autophagy contributes to crizotinib resistance in ALK-positive anaplastic large cell lymphoma (ALK + ALCL).	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	79-82
33430343-1	2021	Previously it was shown that autophagy contributes to crizotinib resistance in ALK-positive anaplastic large cell lymphoma (ALK + ALCL).	Crizotinib	54-64	ALK receptor tyrosine kinase	Homo sapiens	124-127
33380260-9	2021	Furthermore, we also demonstrate the sequential use of crizotinib, brigatinib, and lorlatinib in a patient with advanced ALK-rearranged lung adenocarcinoma with an overall progression-free survival of 33.3 months for the sequential ALK inhibitor regimens.	Crizotinib	55-65	ALK receptor tyrosine kinase	Homo sapiens	232-235
33227290-1	2021	Cell based studies have suggested that the diabetes drug metformin may combine with the anaplastic lymphoma kinase receptor (ALK) inhibitor crizotinib to increase ALK positive lung cancer cell killing and overcome crizotinib resistance.	Crizotinib	140-150	anaplastic lymphoma kinase	Mus musculus	88-123
33227290-1	2021	Cell based studies have suggested that the diabetes drug metformin may combine with the anaplastic lymphoma kinase receptor (ALK) inhibitor crizotinib to increase ALK positive lung cancer cell killing and overcome crizotinib resistance.	Crizotinib	140-150	anaplastic lymphoma kinase	Mus musculus	125-128
33227290-1	2021	Cell based studies have suggested that the diabetes drug metformin may combine with the anaplastic lymphoma kinase receptor (ALK) inhibitor crizotinib to increase ALK positive lung cancer cell killing and overcome crizotinib resistance.	Crizotinib	140-150	anaplastic lymphoma kinase	Mus musculus	163-166
33227290-1	2021	Cell based studies have suggested that the diabetes drug metformin may combine with the anaplastic lymphoma kinase receptor (ALK) inhibitor crizotinib to increase ALK positive lung cancer cell killing and overcome crizotinib resistance.	Crizotinib	214-224	anaplastic lymphoma kinase	Mus musculus	88-123
33227290-1	2021	Cell based studies have suggested that the diabetes drug metformin may combine with the anaplastic lymphoma kinase receptor (ALK) inhibitor crizotinib to increase ALK positive lung cancer cell killing and overcome crizotinib resistance.	Crizotinib	214-224	anaplastic lymphoma kinase	Mus musculus	125-128
33227290-8	2021	Also, consistent with earlier work, the addition of insulin-like growth factor-1 (IGF-1) to EML4-ALK positive cancer cells reduced cell killing by crizotinib.	Crizotinib	147-157	insulin-like growth factor 1	Mus musculus	52-80
33227290-8	2021	Also, consistent with earlier work, the addition of insulin-like growth factor-1 (IGF-1) to EML4-ALK positive cancer cells reduced cell killing by crizotinib.	Crizotinib	147-157	insulin like growth factor 1	Homo sapiens	82-87
33227290-8	2021	Also, consistent with earlier work, the addition of insulin-like growth factor-1 (IGF-1) to EML4-ALK positive cancer cells reduced cell killing by crizotinib.	Crizotinib	147-157	EMAP like 4	Homo sapiens	92-96
33227290-8	2021	Also, consistent with earlier work, the addition of insulin-like growth factor-1 (IGF-1) to EML4-ALK positive cancer cells reduced cell killing by crizotinib.	Crizotinib	147-157	ALK receptor tyrosine kinase	Homo sapiens	97-100
33945921-2	2021	Here, we present a metastatic lung adenocarcinoma patient harboring a CD74-ROS1 fusion who initially responded to crizotinib and then developed resistance after acquiring a rarely reported BRAF V600E mutation.	Crizotinib	114-124	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	75-79
33430343-5	2021	Their exaggerated autophagic response is cytoprotective against crizotinib, as inhibition of autophagy using chloroquine or shRNA against BECN1 or ATG7 led to a decrease in their viability.	Crizotinib	64-74	beclin 1	Homo sapiens	138-143
33430343-5	2021	Their exaggerated autophagic response is cytoprotective against crizotinib, as inhibition of autophagy using chloroquine or shRNA against BECN1 or ATG7 led to a decrease in their viability.	Crizotinib	64-74	autophagy related 7	Homo sapiens	147-151
33082208-0	2021	Overcoming MET-dependent resistance to selective RET inhibition in patients with RET fusion-positive lung cancer by combining selpercatinib with crizotinib.	Crizotinib	145-155	SAFB like transcription modulator	Homo sapiens	11-14
33082208-0	2021	Overcoming MET-dependent resistance to selective RET inhibition in patients with RET fusion-positive lung cancer by combining selpercatinib with crizotinib.	Crizotinib	145-155	ret proto-oncogene	Homo sapiens	49-52
33082208-0	2021	Overcoming MET-dependent resistance to selective RET inhibition in patients with RET fusion-positive lung cancer by combining selpercatinib with crizotinib.	Crizotinib	145-155	ret proto-oncogene	Homo sapiens	81-84
33082208-8	2021	We demonstrate that increased MET expression in RET fusion-positive tumor cells causes resistance to selpercatinib, and this can be overcome by combining selpercatinib with crizotinib.	Crizotinib	173-183	SAFB like transcription modulator	Homo sapiens	30-33
33082208-8	2021	We demonstrate that increased MET expression in RET fusion-positive tumor cells causes resistance to selpercatinib, and this can be overcome by combining selpercatinib with crizotinib.	Crizotinib	173-183	ret proto-oncogene	Homo sapiens	48-51
32778510-0	2021	A Case of Resistance to Selective RET-TKI Therapy With Pleural-Genotyped MET Amplification and Response to Crizotinib.	Crizotinib	107-117	ret proto-oncogene	Homo sapiens	34-37
33402581-0	2021	Successful combination of crizotinib and hematopoietic stem cell transplantation in relapsed ALK-positive ALCL.	Crizotinib	26-36	ALK receptor tyrosine kinase	Homo sapiens	93-96
33402581-1	2021	We report a case wherein a combination of crizotinib and hematopoietic stem cell transplantation (HSCT) cured a 20-year-old woman with relapsed and refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-positive ALCL).	Crizotinib	42-52	ALK receptor tyrosine kinase	Homo sapiens	227-230
33402581-4	2021	Therefore, the patient received off-label use of crizotinib (an ALK inhibitor) and her condition improved rapidly.	Crizotinib	49-59	ALK receptor tyrosine kinase	Homo sapiens	64-67
32980960-7	2021	Cell proliferation assay was used to assess the effect of crizotinib and tivantinib on the six liver cancer cell lines in correlation with the expression of MET, L1-MET and MET.	Crizotinib	58-68	SAFB like transcription modulator	Homo sapiens	157-160
32980960-7	2021	Cell proliferation assay was used to assess the effect of crizotinib and tivantinib on the six liver cancer cell lines in correlation with the expression of MET, L1-MET and MET.	Crizotinib	58-68	SAFB like transcription modulator	Homo sapiens	165-168
32980960-8	2021	RESULTS: The antitumor effect of crizotinib and tivantinib correlated with MET gene expression but not with L1-MET transcript or MET protein expressions.	Crizotinib	33-43	SAFB like transcription modulator	Homo sapiens	75-78
32980960-11	2021	CONCLUSION: MET RNA expression could be useful biomarker for tivantinib and crizotinib targeted therapy in HCC.	Crizotinib	76-86	SAFB like transcription modulator	Homo sapiens	12-15
33403024-0	2021	Genomic and clinical characteristics of MET exon14 alterations in a large cohort of Chinese cancer patients revealed distinct features and a novel resistance mechanism for crizotinib.	Crizotinib	172-182	SAFB like transcription modulator	Homo sapiens	40-43
33403024-2	2021	Patients with METex14 alterations often benefit from MET inhibitors such as crizotinib.	Crizotinib	76-86	SAFB like transcription modulator	Homo sapiens	14-17
33403024-13	2021	Upon resistance to crizotinib, two patients acquired secondary mutations in MET and one patient acquired BRAF p.K601E that can be a novel resistance mechanism.	Crizotinib	19-29	SAFB like transcription modulator	Homo sapiens	76-79
33403024-13	2021	Upon resistance to crizotinib, two patients acquired secondary mutations in MET and one patient acquired BRAF p.K601E that can be a novel resistance mechanism.	Crizotinib	19-29	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	105-109
33001162-0	2021	Progressive Dry Cough in a Patient With ROS1-Rearranged Lung Adenocarcinoma Undergoing Crizotinib Therapy.	Crizotinib	87-97	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	40-44
33280926-0	2021	A novel HIP1-ALK fusion variant in lung adenocarcinoma showing resistance to Crizotinib.	Crizotinib	77-87	huntingtin interacting protein 1	Homo sapiens	8-12
33280926-0	2021	A novel HIP1-ALK fusion variant in lung adenocarcinoma showing resistance to Crizotinib.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	13-16
33281972-1	2021	Crizotinib, an inhibitor of the hepatocyte growth factor receptor oncogene, has been studied extensively regarding its antitumor and clinically beneficial effects in non-small cell lung cancer (NSCLC).	Crizotinib	0-10	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	32-65
33430343-8	2021	Inhibition of MYC in RR cells using shRNA significantly blunted crizotinib-induced autophagic response and effectively suppressed this cytoprotective effect.	Crizotinib	64-74	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	14-17
33200229-3	2021	A series of studies have indicated that ALK-TKI agents as the first-line treatment, including crizotinib, ceritinib, brigatinib, alectinib and entrectinib, can benefit patients with ALK-positive NSCLC.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	40-43
33200229-3	2021	A series of studies have indicated that ALK-TKI agents as the first-line treatment, including crizotinib, ceritinib, brigatinib, alectinib and entrectinib, can benefit patients with ALK-positive NSCLC.	Crizotinib	94-104	ALK receptor tyrosine kinase	Homo sapiens	182-185
33348616-5	2020	Treatment with crizotinib suppressed the growth of tumors formed by the EML4-ALK-expressing lung epithelial cells in a subcutaneous transplantation model.	Crizotinib	15-25	EMAP like 4	Homo sapiens	72-76
33129112-4	2021	We found that EGF and tumor growth factor alpha (TGFalpha) significantly decreased the antiproliferative activity of the RET inhibitor BLU-667 in CCDC6-RET cells and brigatinib, alectinib and crizotinib in EML4-ALK translocated cells.	Crizotinib	192-202	epidermal growth factor	Homo sapiens	14-17
33129112-4	2021	We found that EGF and tumor growth factor alpha (TGFalpha) significantly decreased the antiproliferative activity of the RET inhibitor BLU-667 in CCDC6-RET cells and brigatinib, alectinib and crizotinib in EML4-ALK translocated cells.	Crizotinib	192-202	transforming growth factor alpha	Homo sapiens	49-57
33374879-7	2020	The patient with METDeltaex14 had a partial response to tepotinib, one of the patients with ALK fusions was treated with crizotinib with a complete response.	Crizotinib	121-131	ALK receptor tyrosine kinase	Homo sapiens	92-95
33352844-3	2020	The discovery of the EML4-ALK fusion gene in a limited subset of patients affected by NSCLC and the subsequent clinical development of crizotinib in 2011 has been an impressive milestone in lung cancer research.	Crizotinib	135-145	EMAP like 4	Homo sapiens	21-25
33352844-3	2020	The discovery of the EML4-ALK fusion gene in a limited subset of patients affected by NSCLC and the subsequent clinical development of crizotinib in 2011 has been an impressive milestone in lung cancer research.	Crizotinib	135-145	ALK receptor tyrosine kinase	Homo sapiens	26-29
33348616-5	2020	Treatment with crizotinib suppressed the growth of tumors formed by the EML4-ALK-expressing lung epithelial cells in a subcutaneous transplantation model.	Crizotinib	15-25	ALK receptor tyrosine kinase	Homo sapiens	77-80
32462394-14	2020	CONCLUSION: Brigatinib demonstrated modest activity in crizotinib-resistant ROS1-rearranged NSCLC.	Crizotinib	55-65	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	76-80
32943461-2	2020	We conducted a phase 1 trial investigating the safety and pharmacokinetics of a potent c-MET inhibitor crizotinib with the AR antagonist enzalutamide in CRPC.	Crizotinib	103-113	MET proto-oncogene, receptor tyrosine kinase	Homo sapiens	87-92
32943461-2	2020	We conducted a phase 1 trial investigating the safety and pharmacokinetics of a potent c-MET inhibitor crizotinib with the AR antagonist enzalutamide in CRPC.	Crizotinib	103-113	androgen receptor	Homo sapiens	123-125
33865115-0	2021	Complex renal cysts combined with hemorrhage during crizotinib treatment for ALK-rearranged lung adenocarcinoma.	Crizotinib	52-62	ALK receptor tyrosine kinase	Homo sapiens	77-80
33865115-1	2021	The oral small-molecule tyrosine kinase inhibitor (TKI), crizotinib has been approved as a first-generation anaplastic lymphoma kinase (ALK) inhibitor in treatment of advanced ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	57-67	ALK receptor tyrosine kinase	Homo sapiens	108-134
33865115-1	2021	The oral small-molecule tyrosine kinase inhibitor (TKI), crizotinib has been approved as a first-generation anaplastic lymphoma kinase (ALK) inhibitor in treatment of advanced ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	57-67	ALK receptor tyrosine kinase	Homo sapiens	136-139
33865115-1	2021	The oral small-molecule tyrosine kinase inhibitor (TKI), crizotinib has been approved as a first-generation anaplastic lymphoma kinase (ALK) inhibitor in treatment of advanced ALK-positive non-small cell lung cancer (NSCLC).	Crizotinib	57-67	ALK receptor tyrosine kinase	Homo sapiens	176-179
33865115-3	2021	Here we describe a case study with confirmed EGFR wild-type and ALK-rearranged lung adenocarcinoma who developed complex renal cysts combined with hemorrhage during crizotinib treatment, with no abnormal clinical symptoms or kidney functions observed.	Crizotinib	165-175	epidermal growth factor receptor	Homo sapiens	45-49
33865115-3	2021	Here we describe a case study with confirmed EGFR wild-type and ALK-rearranged lung adenocarcinoma who developed complex renal cysts combined with hemorrhage during crizotinib treatment, with no abnormal clinical symptoms or kidney functions observed.	Crizotinib	165-175	ALK receptor tyrosine kinase	Homo sapiens	64-67
33945921-0	2021	Crizotinib resistance conferred by BRAF V600E mutation in non-small cell lung cancer harboring an oncogenic ROS1 fusion.	Crizotinib	0-10	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	35-39
33945921-0	2021	Crizotinib resistance conferred by BRAF V600E mutation in non-small cell lung cancer harboring an oncogenic ROS1 fusion.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	108-112
33945921-2	2021	Here, we present a metastatic lung adenocarcinoma patient harboring a CD74-ROS1 fusion who initially responded to crizotinib and then developed resistance after acquiring a rarely reported BRAF V600E mutation.	Crizotinib	114-124	CD74 molecule	Homo sapiens	70-74
33363027-3	2020	Methods: Ninety-eight ALK-positive patients with advanced NSCLC were retrospectively studied for their response to crizotinib and subsequent treatments.	Crizotinib	115-125	ALK receptor tyrosine kinase	Homo sapiens	22-25
33363027-7	2020	The objective response rate and median progression-free survival to crizotinib treatment tended to be better in the complex ALK fusion group.	Crizotinib	68-78	ALK receptor tyrosine kinase	Homo sapiens	124-127
33363027-8	2020	Notably, patients with complex ALK fusions had significantly improved overall survival after crizotinib treatment (p = 0.012), especially when compared with the pure canonical EML4-ALK fusion group (p = 0.010).	Crizotinib	93-103	ALK receptor tyrosine kinase	Homo sapiens	31-34
33363027-8	2020	Notably, patients with complex ALK fusions had significantly improved overall survival after crizotinib treatment (p = 0.012), especially when compared with the pure canonical EML4-ALK fusion group (p = 0.010).	Crizotinib	93-103	EMAP like 4	Homo sapiens	176-180
33363027-8	2020	Notably, patients with complex ALK fusions had significantly improved overall survival after crizotinib treatment (p = 0.012), especially when compared with the pure canonical EML4-ALK fusion group (p = 0.010).	Crizotinib	93-103	ALK receptor tyrosine kinase	Homo sapiens	181-184
32808682-0	2020	Phase two study of crizotinib in patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma relapsed/refractory to chemotherapy.	Crizotinib	19-29	ALK receptor tyrosine kinase	Homo sapiens	47-73
32808682-0	2020	Phase two study of crizotinib in patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma relapsed/refractory to chemotherapy.	Crizotinib	19-29	ALK receptor tyrosine kinase	Homo sapiens	75-78
33249379-1	2020	BACKGROUND: Patients with anaplastic lymphoma kinase-rearranged (ALK+) non-small cell lung cancer (NSCLC) treated with crizotinib inevitably relapse, with brain as common site of progression.	Crizotinib	119-129	ALK receptor tyrosine kinase	Homo sapiens	65-68
33045465-2	2020	Efficacy of the MET-inhibitor crizotinib has been reported, but progression-free survival (PFS) was very short.	Crizotinib	30-40	SAFB like transcription modulator	Homo sapiens	16-19
33073300-0	2020	Mutation-mediated influences on binding of anaplastic lymphoma kinase to crizotinib decoded by multiple replica Gaussian accelerated molecular dynamics.	Crizotinib	73-83	ALK receptor tyrosine kinase	Homo sapiens	43-69
32897609-0	2020	Identification of a novel EHBP1-MET fusion in an intrahepatic cholangiocarcinoma responding to crizotinib.	Crizotinib	95-105	EH domain binding protein 1	Homo sapiens	26-31
33073300-6	2020	Analyses of free energy landscapes show that stability in the orientation and positions of crizotinib relative to ALK plays a vital role in alleviating drug resistance of mutations toward crizotinib.	Crizotinib	188-198	ALK receptor tyrosine kinase	Homo sapiens	114-117
33073300-8	2020	The results not only indicate that the tuning of point mutation L1198F on interaction networks of crizotinib with ALK can be regarded as a possible strategy to relieve drug resistance of the mutated ALK but also further verify that residues L1122, V1130, L1196, L1198, M1199, and L1256 can be used as efficient targets of anti-drug resistance design induced by mutations.	Crizotinib	98-108	ALK receptor tyrosine kinase	Homo sapiens	114-117
33073300-8	2020	The results not only indicate that the tuning of point mutation L1198F on interaction networks of crizotinib with ALK can be regarded as a possible strategy to relieve drug resistance of the mutated ALK but also further verify that residues L1122, V1130, L1196, L1198, M1199, and L1256 can be used as efficient targets of anti-drug resistance design induced by mutations.	Crizotinib	98-108	ALK receptor tyrosine kinase	Homo sapiens	199-202
33262326-6	2020	For instance, we confirm a novel synergy between anaplastic lymphoma kinase (ALK) inhibitor crizotinib and proteasome inhibitor bortezomib in lymphoma cells.	Crizotinib	92-102	ALK receptor tyrosine kinase	Homo sapiens	49-75
33262326-6	2020	For instance, we confirm a novel synergy between anaplastic lymphoma kinase (ALK) inhibitor crizotinib and proteasome inhibitor bortezomib in lymphoma cells.	Crizotinib	92-102	ALK receptor tyrosine kinase	Homo sapiens	77-80
32897609-0	2020	Identification of a novel EHBP1-MET fusion in an intrahepatic cholangiocarcinoma responding to crizotinib.	Crizotinib	95-105	SAFB like transcription modulator	Homo sapiens	32-35
32897609-7	2020	Subsequently, the patient started treatment with MET inhibitors crizotinib.	Crizotinib	64-74	SAFB like transcription modulator	Homo sapiens	49-52
32897609-9	2020	To the best of our knowledge, this is the first clinical case report of a MET rearranged-ICC patient successfully treated with crizotinib.	Crizotinib	127-137	SAFB like transcription modulator	Homo sapiens	74-77
32897609-10	2020	This case suggests that crizotinib may be a promising treatment option for ICC patients with MET fusion, warranting further clinical investigation.	Crizotinib	24-34	SAFB like transcription modulator	Homo sapiens	93-96
32897609-12	2020	This is also the first clinical case report of clinical benefit from crizotinib treatment in an ICC with MET fusion.	Crizotinib	69-79	SAFB like transcription modulator	Homo sapiens	105-108
33489809-0	2020	Coexistence of a novel CCNY-ALK and ATIC-ALK double-fusion in one patient with ALK-positive NSCLC and response to crizotinib: a case report.	Crizotinib	114-124	cyclin Y	Homo sapiens	23-27
33457258-4	2020	Combined Immunohistology (IHC) and fluorescence in situ hybridization (FISH) revealed the patient has an ALK rearrangement, and the patient then was treated with crizotinib.	Crizotinib	162-172	ALK receptor tyrosine kinase	Homo sapiens	105-108
33489809-0	2020	Coexistence of a novel CCNY-ALK and ATIC-ALK double-fusion in one patient with ALK-positive NSCLC and response to crizotinib: a case report.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	28-31
33457258-11	2020	Our case demonstrated the efficacy of crizotinib in an RCC patient with ALK rearrangement.	Crizotinib	38-48	ALK receptor tyrosine kinase	Homo sapiens	72-75
33489809-0	2020	Coexistence of a novel CCNY-ALK and ATIC-ALK double-fusion in one patient with ALK-positive NSCLC and response to crizotinib: a case report.	Crizotinib	114-124	5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase	Homo sapiens	36-40
33007314-3	2020	Under neoadjuvant treatment with the first generation ALK inhibitor crizotinib no tumour response was seen, but the following therapy with the next generation ALK inhibitor lorlatinib led to a rapid and deep response, enabling a complete tumour resection by partial cystectomy.	Crizotinib	68-78	ALK receptor tyrosine kinase	Homo sapiens	54-57
33007314-4	2020	Our case indicates that ALK positive IMTs which do not respond to ALK inhibition with crizotinib can be successfully treated with newer agents.	Crizotinib	86-96	ALK receptor tyrosine kinase	Homo sapiens	24-27
33489809-0	2020	Coexistence of a novel CCNY-ALK and ATIC-ALK double-fusion in one patient with ALK-positive NSCLC and response to crizotinib: a case report.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	41-44
33489809-0	2020	Coexistence of a novel CCNY-ALK and ATIC-ALK double-fusion in one patient with ALK-positive NSCLC and response to crizotinib: a case report.	Crizotinib	114-124	ALK receptor tyrosine kinase	Homo sapiens	41-44
33489809-2	2020	The earlier phase III PROFILE 1014 study has shown that crizotinib, a first-generation ALK-TKI, significantly improved progression-free survival (PFS) compared with platinum-based chemotherapy in patients with previously untreated advanced ALK-positive NSCLC.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	87-90
33489809-2	2020	The earlier phase III PROFILE 1014 study has shown that crizotinib, a first-generation ALK-TKI, significantly improved progression-free survival (PFS) compared with platinum-based chemotherapy in patients with previously untreated advanced ALK-positive NSCLC.	Crizotinib	56-66	ALK receptor tyrosine kinase	Homo sapiens	240-243
33489815-3	2020	The echinoderm microtubule-associated protein-like (EML)-ALK translocation was first discovered in 2007 and 4 years later, crizotinib, a first-generation ALK inhibitor was approved.	Crizotinib	123-133	ALK receptor tyrosine kinase	Homo sapiens	57-60
33489815-3	2020	The echinoderm microtubule-associated protein-like (EML)-ALK translocation was first discovered in 2007 and 4 years later, crizotinib, a first-generation ALK inhibitor was approved.	Crizotinib	123-133	ALK receptor tyrosine kinase	Homo sapiens	154-157
33489817-5	2020	Less potent ALK inhibitors (ALKi)-like crizotinib-usually tend to induce a large spectrum of secondary intra-kinase mutations; however, these alterations may be observed also after sequential administration of multiple ALKi.	Crizotinib	39-49	ALK receptor tyrosine kinase	Homo sapiens	12-15
33489827-4	2020	A number of trials have supported crizotinib as the best option for NSCLC patients with ROS1 translocations, irrespective of line of therapy.	Crizotinib	34-44	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	88-92
33489827-5	2020	Unfortunately, the majority of patients become insensitive to crizotinib, due to the occurrence of secondary ROS1 mutations or failure within the central nervous system (CNS).	Crizotinib	62-72	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	109-113
33200682-4	2022	Besides the currently available drugs such as Crizotinib and PF-06463922 are becoming sensitive due to mutations in the ROS1 protein.	Crizotinib	46-56	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	120-124
33203201-2	2020	With the in-depth study of the EML4-ALK driver gene, ALK inhibitors represented by crizotinib have been gradually developed and applied in the clinic.	Crizotinib	83-93	EMAP like 4	Homo sapiens	31-35
33203201-2	2020	With the in-depth study of the EML4-ALK driver gene, ALK inhibitors represented by crizotinib have been gradually developed and applied in the clinic.	Crizotinib	83-93	ALK receptor tyrosine kinase	Homo sapiens	36-39
33203201-2	2020	With the in-depth study of the EML4-ALK driver gene, ALK inhibitors represented by crizotinib have been gradually developed and applied in the clinic.	Crizotinib	83-93	ALK receptor tyrosine kinase	Homo sapiens	53-56
33324391-1	2020	The drug resistance of first-line crizotinib therapy for ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) fusion non-small cell lung cancer (NSCLC) is inevitable.	Crizotinib	34-44	ret proto-oncogene	Homo sapiens	79-103
33324391-1	2020	The drug resistance of first-line crizotinib therapy for ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) fusion non-small cell lung cancer (NSCLC) is inevitable.	Crizotinib	34-44	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	105-109
33324391-4	2020	Ba/F3 cells expressing crizotinib sensitive ROS1 fusion and crizotinib resistant ROS1-G2032R mutation were used to explore the relationship between ROS1 fusion, ROS1-G2032R mutation and programmed death-ligand 1 (PD-L1) expression and the clinical potential of anti-PD-L1 ICI therapy.	Crizotinib	23-33	Ros1 proto-oncogene	Mus musculus	44-48
33201727-0	2021	The tyrosine kinase inhibitor crizotinib influences blood glucose and mRNA expression of GLUT4 and PPARs in the heart of rats with experimental diabetes.	Crizotinib	30-40	solute carrier family 2 member 4	Rattus norvegicus	89-94
33201727-12	2021	However, an mRNA downregulation of insulin-dependent glucose transporter Glut4 in hearts of STZ rats was attenuated after crizotinib treatment.	Crizotinib	122-132	solute carrier family 2 member 4	Rattus norvegicus	73-78
33201727-13	2021	Moreover, crizotinib normalized Ppard and reduced Pparg mRNA expression in diabetic hearts.	Crizotinib	10-20	peroxisome proliferator-activated receptor gamma	Rattus norvegicus	50-55
33204104-0	2020	A Novel ROS1-FBXL17 Fusion Co-Existing with CD74-ROS1 Fusion May Improve Sensitivity to Crizotinib and Prolong Progression-Free Survival of Patients with Lung Adenocarcinoma.	Crizotinib	88-98	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	8-12
33186133-0	2020	Crizotinib plus erlotinib overcomes osimertinib resistance in a seriously-ill non-small cell lung cancer patient with acquired MET amplification.	Crizotinib	0-10	SAFB like transcription modulator	Homo sapiens	127-130
33204104-0	2020	A Novel ROS1-FBXL17 Fusion Co-Existing with CD74-ROS1 Fusion May Improve Sensitivity to Crizotinib and Prolong Progression-Free Survival of Patients with Lung Adenocarcinoma.	Crizotinib	88-98	F-box and leucine rich repeat protein 17	Homo sapiens	13-19
33204104-0	2020	A Novel ROS1-FBXL17 Fusion Co-Existing with CD74-ROS1 Fusion May Improve Sensitivity to Crizotinib and Prolong Progression-Free Survival of Patients with Lung Adenocarcinoma.	Crizotinib	88-98	CD74 molecule	Homo sapiens	44-48
33204104-0	2020	A Novel ROS1-FBXL17 Fusion Co-Existing with CD74-ROS1 Fusion May Improve Sensitivity to Crizotinib and Prolong Progression-Free Survival of Patients with Lung Adenocarcinoma.	Crizotinib	88-98	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	49-53
33204104-2	2020	Currently, only approximately 24 ROS1 fusion partners have been shown to be sensitive to crizotinib.	Crizotinib	89-99	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	33-37
33204104-7	2020	We identified a non-reciprocal/reciprocal ROS1 translocation which contained a novel ROS1-FBXL17 (F-box and leucine-rich repeat protein 17) fusion co-existing with the CD74-ROS1 fusion and the patient was sensitive to crizotinib.	Crizotinib	218-228	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	42-46
33204104-7	2020	We identified a non-reciprocal/reciprocal ROS1 translocation which contained a novel ROS1-FBXL17 (F-box and leucine-rich repeat protein 17) fusion co-existing with the CD74-ROS1 fusion and the patient was sensitive to crizotinib.	Crizotinib	218-228	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	85-89
33204104-7	2020	We identified a non-reciprocal/reciprocal ROS1 translocation which contained a novel ROS1-FBXL17 (F-box and leucine-rich repeat protein 17) fusion co-existing with the CD74-ROS1 fusion and the patient was sensitive to crizotinib.	Crizotinib	218-228	F-box and leucine rich repeat protein 17	Homo sapiens	90-96
33204104-7	2020	We identified a non-reciprocal/reciprocal ROS1 translocation which contained a novel ROS1-FBXL17 (F-box and leucine-rich repeat protein 17) fusion co-existing with the CD74-ROS1 fusion and the patient was sensitive to crizotinib.	Crizotinib	218-228	CD74 molecule	Homo sapiens	168-172
33204104-7	2020	We identified a non-reciprocal/reciprocal ROS1 translocation which contained a novel ROS1-FBXL17 (F-box and leucine-rich repeat protein 17) fusion co-existing with the CD74-ROS1 fusion and the patient was sensitive to crizotinib.	Crizotinib	218-228	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	85-89
33204104-10	2020	Thus, this non-reciprocal/reciprocal ROS1 translocation patient had an excellent efficacy to crizotinib which was different from that in ALK.	Crizotinib	93-103	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	37-41
33204104-11	2020	And it may be possible that the ROS1-FBXL17 fusion in this patient synergistically promotes the sensitivity of the CD74-RSO1 fusion to crizotinib.	Crizotinib	135-145	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	32-36
33204104-11	2020	And it may be possible that the ROS1-FBXL17 fusion in this patient synergistically promotes the sensitivity of the CD74-RSO1 fusion to crizotinib.	Crizotinib	135-145	F-box and leucine rich repeat protein 17	Homo sapiens	37-43
33204104-11	2020	And it may be possible that the ROS1-FBXL17 fusion in this patient synergistically promotes the sensitivity of the CD74-RSO1 fusion to crizotinib.	Crizotinib	135-145	CD74 molecule	Homo sapiens	115-119
33204104-12	2020	Conclusion: The ROS1-FBXL17 fusion may be a novel driver of NSCLC and we provide a non-reciprocal/reciprocal ROS1 translocation mode very sensitive to crizotinib.	Crizotinib	151-161	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	16-20
33204104-12	2020	Conclusion: The ROS1-FBXL17 fusion may be a novel driver of NSCLC and we provide a non-reciprocal/reciprocal ROS1 translocation mode very sensitive to crizotinib.	Crizotinib	151-161	F-box and leucine rich repeat protein 17	Homo sapiens	21-27
33204104-12	2020	Conclusion: The ROS1-FBXL17 fusion may be a novel driver of NSCLC and we provide a non-reciprocal/reciprocal ROS1 translocation mode very sensitive to crizotinib.	Crizotinib	151-161	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	109-113
33172113-0	2020	Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies.	Crizotinib	59-69	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	9-13
33172113-3	2020	ROS1 is currently targeted by several specific tyrosine kinase inhibitors (TKIs), but only two of these, crizotinib and entrectinib, have received Food and Drug Administration (FDA) approval.	Crizotinib	105-115	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	0-4
33172113-4	2020	Crizotinib is a low molecular weight, orally available TKI that inhibits ROS1, MET and ALK and is considered the gold standard first-line treatment with demonstrated significant activity for lung cancers harbouring ROS1 gene rearrangements.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	73-77
33172113-4	2020	Crizotinib is a low molecular weight, orally available TKI that inhibits ROS1, MET and ALK and is considered the gold standard first-line treatment with demonstrated significant activity for lung cancers harbouring ROS1 gene rearrangements.	Crizotinib	0-10	SAFB like transcription modulator	Homo sapiens	79-82
33172113-4	2020	Crizotinib is a low molecular weight, orally available TKI that inhibits ROS1, MET and ALK and is considered the gold standard first-line treatment with demonstrated significant activity for lung cancers harbouring ROS1 gene rearrangements.	Crizotinib	0-10	ALK receptor tyrosine kinase	Homo sapiens	87-90
33172113-4	2020	Crizotinib is a low molecular weight, orally available TKI that inhibits ROS1, MET and ALK and is considered the gold standard first-line treatment with demonstrated significant activity for lung cancers harbouring ROS1 gene rearrangements.	Crizotinib	0-10	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	215-219
33172113-5	2020	However, crizotinib resistance often occurs, making the treatment of ROS1-positive lung cancers more challenging.	Crizotinib	9-19	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	69-73
33251146-4	2020	We developed a reproducible process to select a single phase II trial and supporting preclinical publication for a given drug-indication pair, which we defined as the pairing of a small molecule inhibitor (e.g., crizotinib) with the specific patient population for which it was designed to work (e.g., patients with an ALK aberration).	Crizotinib	212-222	ALK receptor tyrosine kinase	Homo sapiens	319-322
33157918-0	2020	A rare double ALK fusion variant EML4-ALK and CDK15-ALK in lung adenocarcinoma and response to crizotinib: A case report.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	14-17
33157918-0	2020	A rare double ALK fusion variant EML4-ALK and CDK15-ALK in lung adenocarcinoma and response to crizotinib: A case report.	Crizotinib	95-105	EMAP like 4	Homo sapiens	33-37
33157918-0	2020	A rare double ALK fusion variant EML4-ALK and CDK15-ALK in lung adenocarcinoma and response to crizotinib: A case report.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	38-41
33157918-0	2020	A rare double ALK fusion variant EML4-ALK and CDK15-ALK in lung adenocarcinoma and response to crizotinib: A case report.	Crizotinib	95-105	cyclin dependent kinase 15	Homo sapiens	46-51
33157918-0	2020	A rare double ALK fusion variant EML4-ALK and CDK15-ALK in lung adenocarcinoma and response to crizotinib: A case report.	Crizotinib	95-105	ALK receptor tyrosine kinase	Homo sapiens	38-41
33153004-7	2020	Anaplastic lymphoma kinase (ALK) is the target for drugs such as crizotinib, alectinib, ceritinib.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	0-26
33153004-7	2020	Anaplastic lymphoma kinase (ALK) is the target for drugs such as crizotinib, alectinib, ceritinib.	Crizotinib	65-75	ALK receptor tyrosine kinase	Homo sapiens	28-31
32827692-6	2020	These beneficial effects of HGF were blocked by HGF/c-Met inhibitor Crizotinib or phosphatidylinositide 3-kinases (PI3K) inhibitor LY294002.	Crizotinib	68-78	hepatocyte growth factor	Mus musculus	28-31
32827692-6	2020	These beneficial effects of HGF were blocked by HGF/c-Met inhibitor Crizotinib or phosphatidylinositide 3-kinases (PI3K) inhibitor LY294002.	Crizotinib	68-78	hepatocyte growth factor	Mus musculus	48-51
32827692-6	2020	These beneficial effects of HGF were blocked by HGF/c-Met inhibitor Crizotinib or phosphatidylinositide 3-kinases (PI3K) inhibitor LY294002.	Crizotinib	68-78	met proto-oncogene	Mus musculus	52-57
32949827-0	2020	Characteristics and response to crizotinib in lung cancer patients with MET amplification detected by next-generation sequencing.	Crizotinib	32-42	SAFB like transcription modulator	Homo sapiens	72-75
32871626-2	2020	The tyrosine kinase inhibitors (TKIs), crizotinib, lorlatinib, and entrectinib have demonstrated favorable efficacy in treating ROS1-rearranged NSCLCs.	Crizotinib	39-49	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	128-132
32576444-0	2020	Chr2 30297612-ALK, A Novel Intergenic Fusion With Exon18 of ALK, Responds to Crizotinib.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	14-17
32576444-0	2020	Chr2 30297612-ALK, A Novel Intergenic Fusion With Exon18 of ALK, Responds to Crizotinib.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	60-63
32620469-0	2020	Combining EGFR and MET Inhibition With Crizotinib in EGFR-mutated Lung Adenocarcinoma Harboring MET Amplification: A Brief Report.	Crizotinib	39-49	epidermal growth factor receptor	Homo sapiens	53-57
33046892-6	2020	For instance, ALK-rearranged renal cell carcinomas have shown responses to alectinib and crizotinib.	Crizotinib	89-99	ALK receptor tyrosine kinase	Homo sapiens	14-17
32652753-0	2020	Successful Treatment of Patients with Refractory High-Grade Serous Ovarian Cancer with GOPC-ROS1 Fusion Using Crizotinib: A Case Report.	Crizotinib	110-120	golgi associated PDZ and coiled-coil motif containing	Homo sapiens	87-91
32652753-0	2020	Successful Treatment of Patients with Refractory High-Grade Serous Ovarian Cancer with GOPC-ROS1 Fusion Using Crizotinib: A Case Report.	Crizotinib	110-120	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	92-96
32652753-9	2020	CONCLUSION: This study suggested that crizotinib was an off-the-shelf, practical, and ostensibly effective treatment option for patients with ovarian cancer with ROS1 rearrangement.	Crizotinib	38-48	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	162-166
32652753-14	2020	This study suggests that comprehensive sequencing should be offered for patients with ovarian cancer without effective therapeutic strategies, and crizotinib can be used to treat ROS1-rearranged ovarian carcinomas.	Crizotinib	147-157	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	179-183
33082316-0	2020	Inhibiting insulin and mTOR signaling by afatinib and crizotinib combination fosters broad cytotoxic effects in cutaneous malignant melanoma.	Crizotinib	54-64	insulin	Homo sapiens	11-18
33082316-0	2020	Inhibiting insulin and mTOR signaling by afatinib and crizotinib combination fosters broad cytotoxic effects in cutaneous malignant melanoma.	Crizotinib	54-64	mechanistic target of rapamycin kinase	Homo sapiens	23-27
33082316-5	2020	Our analysis revealed that mTOR/Insulin signaling pathways were significantly decreased by the afatinib and crizotinib combination treatment.	Crizotinib	108-118	mechanistic target of rapamycin kinase	Homo sapiens	27-31
33082316-5	2020	Our analysis revealed that mTOR/Insulin signaling pathways were significantly decreased by the afatinib and crizotinib combination treatment.	Crizotinib	108-118	insulin	Homo sapiens	32-39
33066037-0	2020	High Levels of miR-7-5p Potentiate Crizotinib-Induced Cytokilling and Autophagic Flux by Targeting RAF1 in NPM-ALK Positive Lymphoma Cells.	Crizotinib	35-45	microRNA 7-1	Homo sapiens	15-23
33066037-0	2020	High Levels of miR-7-5p Potentiate Crizotinib-Induced Cytokilling and Autophagic Flux by Targeting RAF1 in NPM-ALK Positive Lymphoma Cells.	Crizotinib	35-45	ALK receptor tyrosine kinase	Homo sapiens	111-114
33066037-2	2020	The therapeutic options comprise chemotherapy, which is efficient in approximately 70% of patients, and targeted therapies, such as crizotinib (an ALK tyrosine kinase inhibitor (TKI)), used in refractory/relapsed cases.	Crizotinib	132-142	ALK receptor tyrosine kinase	Homo sapiens	147-150
33066037-6	2020	We previously demonstrated that crizotinib induced cytoprotective autophagy in ALK+ lymphoma cells and that its further intensification was associated with cell death.	Crizotinib	32-42	ALK receptor tyrosine kinase	Homo sapiens	79-82
33116613-2	2020	They both received tumor resection surgery and treatment with ALK inhibitors crizotinib followed by alectinib, and upon receiving each of the drugs, showed a brief response, then experienced recurrence or progression of the disease.	Crizotinib	77-87	ALK receptor tyrosine kinase	Homo sapiens	62-65
33116613-8	2020	While the expression of PTCH1, a negative regulator of the sonic hedgehog (SHH) signaling pathway, was significantly reduced at the time after the treatment with crizotinib before that of alectinib.	Crizotinib	162-172	patched 1	Homo sapiens	24-29
33116613-8	2020	While the expression of PTCH1, a negative regulator of the sonic hedgehog (SHH) signaling pathway, was significantly reduced at the time after the treatment with crizotinib before that of alectinib.	Crizotinib	162-172	sonic hedgehog signaling molecule	Homo sapiens	59-73
33116613-8	2020	While the expression of PTCH1, a negative regulator of the sonic hedgehog (SHH) signaling pathway, was significantly reduced at the time after the treatment with crizotinib before that of alectinib.	Crizotinib	162-172	sonic hedgehog signaling molecule	Homo sapiens	75-78
33116618-0	2020	Identification of a Novel MPRIP-ROS1 Fusion and Clinical Efficacy of Crizotinib in an Advanced Lung Adenocarcinoma Patient: A Case Report.	Crizotinib	69-79	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	32-36
33116618-1	2020	Objective: ROS1 fusions have been identified in 1-2% of non-small-cell lung cancer (NSCLC) patients; they are validated as a driver of carcinogenesis and could be subjected to inhibition by crizotinib.	Crizotinib	190-200	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	11-15
33116618-2	2020	However, previous studies suggested a variable progression-free survival (PFS) ranging from 9.1 to 20.0 months for crizotinib treatment in ROS1-rearranged NSCLC.	Crizotinib	115-125	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	139-143
33116618-3	2020	Here, we reported a 45-year-old female diagnosed with stage IVB lung adenocarcinoma with multiple lymph nodes and bone metastasis carrying a novel MPRIP-ROS1 fusion, which was identified by RNA-based NGS (next-generation sequencing) and was sensitive to crizotinib treatment.	Crizotinib	254-264	myosin phosphatase Rho interacting protein	Homo sapiens	147-152
33116618-3	2020	Here, we reported a 45-year-old female diagnosed with stage IVB lung adenocarcinoma with multiple lymph nodes and bone metastasis carrying a novel MPRIP-ROS1 fusion, which was identified by RNA-based NGS (next-generation sequencing) and was sensitive to crizotinib treatment.	Crizotinib	254-264	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	153-157
33116618-11	2020	Conclusion: The study identified a novel MPRIP-ROS1 fusion that was sensitive to crizotinib, which provided a new driver of lung adenocarcinoma and potential therapeutic target for crizotinib.	Crizotinib	81-91	myosin phosphatase Rho interacting protein	Homo sapiens	41-46
33116618-11	2020	Conclusion: The study identified a novel MPRIP-ROS1 fusion that was sensitive to crizotinib, which provided a new driver of lung adenocarcinoma and potential therapeutic target for crizotinib.	Crizotinib	81-91	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	47-51
33116618-11	2020	Conclusion: The study identified a novel MPRIP-ROS1 fusion that was sensitive to crizotinib, which provided a new driver of lung adenocarcinoma and potential therapeutic target for crizotinib.	Crizotinib	181-191	myosin phosphatase Rho interacting protein	Homo sapiens	41-46
33116618-11	2020	Conclusion: The study identified a novel MPRIP-ROS1 fusion that was sensitive to crizotinib, which provided a new driver of lung adenocarcinoma and potential therapeutic target for crizotinib.	Crizotinib	181-191	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	47-51
33037240-7	2020	The CAM assay also mimicked the sensitivity of ALK-rearranged H2228 and EGFR-mutated H1975 NSCLC cells to tyrosine kinase inhibitors crizotinib and gefitinib respectively, as well as sensitivity of LNCaP cells to androgen-dependent enzalutamide therapy.	Crizotinib	133-143	ALK receptor tyrosine kinase	Homo sapiens	47-50
33037240-7	2020	The CAM assay also mimicked the sensitivity of ALK-rearranged H2228 and EGFR-mutated H1975 NSCLC cells to tyrosine kinase inhibitors crizotinib and gefitinib respectively, as well as sensitivity of LNCaP cells to androgen-dependent enzalutamide therapy.	Crizotinib	133-143	epidermal growth factor receptor	Homo sapiens	72-76
33134180-0	2020	Unusual Late Relapse of ALK-Positive Anaplastic Large Cell Lymphoma Successfully Cleared Using the ALK-Inhibitor Crizotinib: Case Report.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	24-27
33134180-0	2020	Unusual Late Relapse of ALK-Positive Anaplastic Large Cell Lymphoma Successfully Cleared Using the ALK-Inhibitor Crizotinib: Case Report.	Crizotinib	113-123	ALK receptor tyrosine kinase	Homo sapiens	99-102
33106692-3	2020	Several ALK-TKIs have been established: the first-generation ALK-TKI, crizotinib; second-generation ALK-TKIs, alectinib and ceritinib; and third-generation ALK-TKI, lorlatinib.	Crizotinib	70-80	ALK receptor tyrosine kinase	Homo sapiens	8-11
32871626-9	2020	Furthermore, TP53 was most frequently mutated in patients who progressed on crizotinib, and TP53 mutations were significantly associated with shorter crizotinib PFS.	Crizotinib	76-86	tumor protein p53	Homo sapiens	13-17
32871626-9	2020	Furthermore, TP53 was most frequently mutated in patients who progressed on crizotinib, and TP53 mutations were significantly associated with shorter crizotinib PFS.	Crizotinib	150-160	tumor protein p53	Homo sapiens	92-96
32871626-10	2020	ROS1 mutations, including G2032R were observed in approximately 33% of post-crizotinib samples.	Crizotinib	76-86	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	0-4
32871626-11	2020	Collectively, we report the prevalence of ROS1 fusions in a large-scale NSCLC population, and the efficacy of crizotinib in treating patients with ROS1-rearranged NSCLC.	Crizotinib	110-120	ROS proto-oncogene 1, receptor tyrosine kinase	Homo sapiens	147-151
32949827-2	2020	The aim of this study was to investigate the clinical characteristics of MET amplification in lung cancer and the response to crizotinib by subsets of patients with MET amplification detected by next-generation sequencing (NGS).	Crizotinib	126-136	SAFB like transcription modulator	Homo sapiens	165-168
32949827-4	2020	The efficacy of crizotinib in MET amplification was retrospectively analyzed.	Crizotinib	16-26	SAFB like transcription modulator	Homo sapiens	30-33
33002123-0	2020	Drivers of crizotinib resistance in ALK+ ALCL.	Crizotinib	11-21	ALK receptor tyrosine kinase	Homo sapiens	36-39
32573700-0	2020	IL10RA Modulates Crizotinib Sensitivity in NPM1-ALK-positive Anaplastic Large Cell Lymphoma.	Crizotinib	17-27	interleukin 10 receptor subunit alpha	Homo sapiens	0-6
32573700-0	2020	IL10RA Modulates Crizotinib Sensitivity in NPM1-ALK-positive Anaplastic Large Cell Lymphoma.	Crizotinib	17-27	nucleophosmin 1	Homo sapiens	43-47
32573700-0	2020	IL10RA Modulates Crizotinib Sensitivity in NPM1-ALK-positive Anaplastic Large Cell Lymphoma.	Crizotinib	17-27	ALK receptor tyrosine kinase	Homo sapiens	48-51
32573700-2	2020	ALK inhibitors such as crizotinib provide alternatives to standard chemotherapy with reduced toxicity and side effects.	Crizotinib	23-33	ALK receptor tyrosine kinase	Homo sapiens	0-3
32573700-6	2020	Through genome-wide CRISPR activation and knockout screens in ALCL cell lines combined with RNA-seq data derived from ALK inhibitor relapsed patient tumors, we show that resistance to ALK inhibition by crizotinib in ALCL can be driven by aberrant upregulation of IL10RA.	Crizotinib	202-212	ALK receptor tyrosine kinase	Homo sapiens	118-121
32573700-6	2020	Through genome-wide CRISPR activation and knockout screens in ALCL cell lines combined with RNA-seq data derived from ALK inhibitor relapsed patient tumors, we show that resistance to ALK inhibition by crizotinib in ALCL can be driven by aberrant upregulation of IL10RA.	Crizotinib	202-212	ALK receptor tyrosine kinase	Homo sapiens	184-187
32573700-6	2020	Through genome-wide CRISPR activation and knockout screens in ALCL cell lines combined with RNA-seq data derived from ALK inhibitor relapsed patient tumors, we show that resistance to ALK inhibition by crizotinib in ALCL can be driven by aberrant upregulation of IL10RA.	Crizotinib	202-212	interleukin 10 receptor subunit alpha	Homo sapiens	263-269
32573700-8	2020	IL10RA expression does not correlate with response to standard chemotherapy in pediatric patients suggesting that combination of crizotinib with chemotherapy could prevent ALK-inhibitor resistance-specific relapse.	Crizotinib	129-139	interleukin 10 receptor subunit alpha	Homo sapiens	0-6
32573700-8	2020	IL10RA expression does not correlate with response to standard chemotherapy in pediatric patients suggesting that combination of crizotinib with chemotherapy could prevent ALK-inhibitor resistance-specific relapse.	Crizotinib	129-139	ALK receptor tyrosine kinase	Homo sapiens	172-175