PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 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 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 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 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 111-115 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 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 33685866-1 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 45-49 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 33841676-1 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 33841676-3 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 123-128 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 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 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 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 33000474-1 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 73-77 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 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 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 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 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 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 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 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 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 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 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 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 33204104-12 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 109-113 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 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 47-51 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 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 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 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 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 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 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 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 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 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 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 32865687-12 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 32865687-13 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 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 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 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 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 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 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 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 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 32168429-11 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 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 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 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 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 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 32158297-11 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 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 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 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 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 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 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 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 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 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 31639374-6 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 31639374-7 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 8-12 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 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 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 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 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 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 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 67-71 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 169-173 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 29981925-13 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 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 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 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 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 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 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 30053332-13 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 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 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 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 29663378-10 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 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 114-118 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 68-72 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 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 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 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 29477381-2 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 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 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 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 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 107-111 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 136-140 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 59-63 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 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 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 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 29610289-8 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 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 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 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 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 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 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 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 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 29187012-4 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 29187012-8 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 128-132 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 89-93 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 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 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 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 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 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 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 225-235 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 113-117 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 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 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 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 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 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 165-169 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 338-342 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 27561802-6 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 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 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 22-26 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 123-127 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 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 140-150 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 122-126 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 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 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 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 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 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 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 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 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 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 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 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 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 26554404-7 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 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 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 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 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 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 207-211 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 70-74 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 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 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 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 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 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 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 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 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 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 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 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 244-248 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 111-115 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 25688157-12 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 25688157-13 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 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 25999733-7 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 94-98 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 58-62 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 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 23790969-5 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 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 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 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 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 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 101-105 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 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 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 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 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 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 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 78-82 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 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 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 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 22617245-8 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 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 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 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 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 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 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 22989574-4 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 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 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 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 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 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 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 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 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 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 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 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 34660618-1 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 34660618-4 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 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 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 34715804-11 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 25-29 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 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 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 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 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 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 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 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 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 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 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 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 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 34211840-5 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 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 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 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 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 ROS proto-oncogene 1, receptor tyrosine kinase Homo sapiens 118-122 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 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 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 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 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 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 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 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 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 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 35284560-0 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 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 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 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 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