PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33052075-1 2020 We analyzed responsiveness of KRAS-mutated CRC cell lines with distinctive MSI status against mitogen-activated protein kinase (MEK) inhibitor (selumetinib; AZD) and/or B-raf proto-oncogene (BRAF) kinase inhibitor (vemurafenib; PLX). AZD 6244 144-155 KRAS proto-oncogene, GTPase Homo sapiens 30-34 33405090-0 2021 Phase II study of selumetinib, an orally active inhibitor of MEK1 and MEK2 kinases, in KRASG12R-mutant pancreatic ductal adenocarcinoma. AZD 6244 18-29 KRAS proto-oncogene, GTPase Homo sapiens 87-91 33273059-7 2021 We demonstrate that AZD0364 in combination with the MEK1/2 inhibitor selumetinib (AZD6244, ARRY142886) enhances efficacy in KRAS mutant preclinical models that are moderately sensitive or resistant to MEK1/2 inhibition. AZD 6244 91-101 KRAS proto-oncogene, GTPase Homo sapiens 124-128 33273059-9 2021 The AZD0364 and selumetinib combination also results in significant tumour regressions in multiple KRAS mutant xenograft models. AZD 6244 16-27 KRAS proto-oncogene, GTPase Homo sapiens 99-103 33137541-0 2021 Targeted inhibition of glutamine metabolism enhances the antitumor effect of selumetinib in KRAS-mutant NSCLC. AZD 6244 77-88 KRAS proto-oncogene, GTPase Homo sapiens 92-96 33137541-5 2021 CB839, an efficient glutaminase inhibitor, synergized with the MEK inhibitor selumetinib to enhance antitumor activity in KRAS-mutant NSCLC cells and xenografts, and the therapeutic response could be well identified by 18F-FDG PET imaging. AZD 6244 77-88 KRAS proto-oncogene, GTPase Homo sapiens 122-126 33296125-0 2021 Phase I Study of Afatinib and Selumetinib in Patients with KRAS-Mutated Colorectal, Non-Small Cell Lung, and Pancreatic Cancer. AZD 6244 30-41 KRAS proto-oncogene, GTPase Homo sapiens 59-63 33273059-7 2021 We demonstrate that AZD0364 in combination with the MEK1/2 inhibitor selumetinib (AZD6244, ARRY142886) enhances efficacy in KRAS mutant preclinical models that are moderately sensitive or resistant to MEK1/2 inhibition. AZD 6244 69-80 KRAS proto-oncogene, GTPase Homo sapiens 124-128 33273059-7 2021 We demonstrate that AZD0364 in combination with the MEK1/2 inhibitor selumetinib (AZD6244, ARRY142886) enhances efficacy in KRAS mutant preclinical models that are moderately sensitive or resistant to MEK1/2 inhibition. AZD 6244 82-89 KRAS proto-oncogene, GTPase Homo sapiens 124-128 31602313-5 2019 A systematic analysis of preclinical data for a failed phase III trial of selumetinib combined with docetaxel in lung cancer suggests potential indications in pancreatic and colorectal cancers with KRAS mutation. AZD 6244 74-85 KRAS proto-oncogene, GTPase Homo sapiens 198-202 32880495-10 2020 A phase II trial showed that the addition of selumetinib to docetaxel improved response rates and progression-free survival (PFS) in chemotherapy-pretreated KRAS-mutated NSCLC patients; however, a subsequent phase III study did not confirm these findings. AZD 6244 45-56 KRAS proto-oncogene, GTPase Homo sapiens 157-161 30706361-8 2019 The treatment of AZD6244 on K-Ras mutations HCT116 cells promoted the activation of JAK2/STAT3 signaling. AZD 6244 17-24 KRAS proto-oncogene, GTPase Homo sapiens 28-33 31200828-0 2019 Selumetinib in patients receiving standard pemetrexed and platinum-based chemotherapy for advanced or metastatic KRAS wildtype or unknown non-squamous non-small cell lung cancer: A randomized, multicenter, phase II study. AZD 6244 0-11 KRAS proto-oncogene, GTPase Homo sapiens 113-117 30867799-3 2019 In KRAS-mutated NSCLC cells, the MEK inhibitor, selumetinib, inhibited cell growth in a dose-dependent manner, and its growth-inhibitory effect was enhanced by combined treatment with the p38 inhibitor LY2228820. AZD 6244 48-59 KRAS proto-oncogene, GTPase Homo sapiens 3-7 28675058-4 2017 Areas covered: A phase II trial in KRAS-mutant NSCLC had shown significant improvements in PFS and ORR in patients treated with selumetinib plus docetaxel compared to docetaxel alone. AZD 6244 128-139 KRAS proto-oncogene, GTPase Homo sapiens 35-39 30579838-0 2019 Schedule-dependent synergistic effects of 5-fluorouracil and selumetinib in KRAS or BRAF mutant colon cancer models. AZD 6244 61-72 KRAS proto-oncogene, GTPase Homo sapiens 76-80 30579838-12 2019 Our results suggest that sequential administration of 5-FU plus selumetinib would be a promising strategy for patients having KRAS or BRAF mutant colon cancers. AZD 6244 64-75 KRAS proto-oncogene, GTPase Homo sapiens 126-130 29045535-1 2017 Background: Combination of selumetinib plus docetaxel provided clinical benefit in a previous phase II trial for patients with KRAS-mutant advanced non-small-cell lung cancer (NSCLC). AZD 6244 27-38 KRAS proto-oncogene, GTPase Homo sapiens 127-131 30042150-2 2018 Preclinical studies demonstrated Wnt pathway overexpression in KRAS-mutant cell lines resistant to the MEK inhibitor, selumetinib. AZD 6244 118-129 KRAS proto-oncogene, GTPase Homo sapiens 63-67 28675058-5 2017 Disappointing data emerged from the next phase III trial in which the addition of selumetinib to docetaxel in patients with advanced KRAS mutant lung cancer did not improve survival or show clinical benefit. AZD 6244 82-93 KRAS proto-oncogene, GTPase Homo sapiens 133-137 27978579-16 2017 Conclusions and Relevance: Dual targeting of the MEK and PI3K/AKT pathways downstream of KRAS by selumetinib plus MK-2206 did not improve overall survival in patients with metastatic pancreatic adenocarcinoma for whom gemcitabine-based chemotherapy had failed. AZD 6244 97-108 KRAS proto-oncogene, GTPase Homo sapiens 89-93 28492898-0 2017 Selumetinib Plus Docetaxel Compared With Docetaxel Alone and Progression-Free Survival in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer: The SELECT-1 Randomized Clinical Trial. AZD 6244 0-11 KRAS proto-oncogene, GTPase Homo sapiens 104-108 28492898-2 2017 Objective: To compare efficacy of the mitogen-activated protein kinase kinase (MEK) inhibitor selumetinib + docetaxel with docetaxel alone as a second-line therapy for advanced KRAS-mutant NSCLC. AZD 6244 94-105 KRAS proto-oncogene, GTPase Homo sapiens 177-181 27467210-3 2016 Selumetinib (AZD6244, ARRY-142886) is a potent and selective inhibitor of MEK1/2 which has demonstrated significant efficacy in combination with docetaxel in patients with KRAS mutant pretreated advanced NSCLC. AZD 6244 0-11 KRAS proto-oncogene, GTPase Homo sapiens 172-176 27467210-3 2016 Selumetinib (AZD6244, ARRY-142886) is a potent and selective inhibitor of MEK1/2 which has demonstrated significant efficacy in combination with docetaxel in patients with KRAS mutant pretreated advanced NSCLC. AZD 6244 13-20 KRAS proto-oncogene, GTPase Homo sapiens 172-176 27467210-3 2016 Selumetinib (AZD6244, ARRY-142886) is a potent and selective inhibitor of MEK1/2 which has demonstrated significant efficacy in combination with docetaxel in patients with KRAS mutant pretreated advanced NSCLC. AZD 6244 22-33 KRAS proto-oncogene, GTPase Homo sapiens 172-176 26893312-3 2016 Preclinical evidence of the activity of MEK inhibitors in KRAS-mutant NSCLC has pushed forward the clinical development of these agents (namely selumetinib and trametinib) in KRAS-mutant NSCLC particularly in combination with other agents. AZD 6244 144-155 KRAS proto-oncogene, GTPase Homo sapiens 58-62 27422710-3 2016 To determine whether additional adaptive resistance mechanisms may coexist, we characterized global phosphoproteomic changes after MEK inhibitor selumetinib (AZD6244) treatment in KRAS-mutant A427 and A549 lung adenocarcinoma cell lines employing mass spectrometry-based phosphoproteomics. AZD 6244 145-156 KRAS proto-oncogene, GTPase Homo sapiens 180-184 26893312-3 2016 Preclinical evidence of the activity of MEK inhibitors in KRAS-mutant NSCLC has pushed forward the clinical development of these agents (namely selumetinib and trametinib) in KRAS-mutant NSCLC particularly in combination with other agents. AZD 6244 144-155 KRAS proto-oncogene, GTPase Homo sapiens 175-179 27068338-10 2016 After re-mining our sequencing data, we found that more than a half of our KRAS mutant NSCLC patients could potentially benefit from the addition of a MEK inhibitor such as selumetinib to standard chemotherapeutic agents. AZD 6244 173-184 KRAS proto-oncogene, GTPase Homo sapiens 75-79 27231576-3 2016 CASE PRESENTATION: In this case report, we present a patient with recurrent LGSOC with KRAS mutation whose tumor has not progressed and who has maintained a good general condition without severe toxicities following treatment with selumetinib for more than 7 years. AZD 6244 231-242 KRAS proto-oncogene, GTPase Homo sapiens 87-91 26837474-0 2016 Study Design and Rationale for a Randomized, Placebo-Controlled, Double-Blind Study to Assess the Efficacy and Safety of Selumetinib in Combination With Docetaxel as Second-Line Treatment in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer (SELECT-1). AZD 6244 121-132 KRAS proto-oncogene, GTPase Homo sapiens 205-209 28154798-4 2016 Here, we mapped global ATP-binding proteomes perturbed by two clinical MEK inhibitors, AZD6244 and MEK162, in KRAS mutant lung cancer cells as a model system harnessing a desthiobiotin-ATP probe coupled with LC-MS/MS. AZD 6244 87-94 KRAS proto-oncogene, GTPase Homo sapiens 110-114 26802155-0 2016 Selumetinib with and without erlotinib in KRAS mutant and KRAS wild-type advanced nonsmall-cell lung cancer. AZD 6244 0-11 KRAS proto-oncogene, GTPase Homo sapiens 42-46 26802155-0 2016 Selumetinib with and without erlotinib in KRAS mutant and KRAS wild-type advanced nonsmall-cell lung cancer. AZD 6244 0-11 KRAS proto-oncogene, GTPase Homo sapiens 58-62 26802155-11 2016 The ORR in the KRAS mutant group was 0% (95% CI 0.0% to 33.6%) for selumetinib alone and 10% (95% CI 2.1% to 26.3%) for the combination. AZD 6244 67-78 KRAS proto-oncogene, GTPase Homo sapiens 15-19 26666244-3 2016 We hypothesized that targeting MEK with selumetinib could overcome resistance to cetuximab in KRAS mutant CRC. AZD 6244 40-51 KRAS proto-oncogene, GTPase Homo sapiens 94-98 27141064-16 2016 It has been reported that cancer cell lines with Kras G12v mutation are more sensitive to selumetinib than cell lines with wild-type Kras. AZD 6244 90-101 KRAS proto-oncogene, GTPase Homo sapiens 49-53 25322874-0 2015 Phase II study of selumetinib (AZD6244, ARRY-142886) plus irinotecan as second-line therapy in patients with K-RAS mutated colorectal cancer. AZD 6244 18-29 KRAS proto-oncogene, GTPase Homo sapiens 109-114 26125448-0 2015 Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer. AZD 6244 66-77 KRAS proto-oncogene, GTPase Homo sapiens 96-100 26125448-1 2015 BACKGROUND: Selumetinib (AZD6244, ARRY-142886)+docetaxel increases median overall survival (OS) and significantly improves progression-free survival (PFS) and objective response rate (ORR) compared with docetaxel alone in patients with KRAS mutant, stage IIIB/IV non-small-cell lung cancer (NSCLC; NCT00890825). AZD 6244 12-23 KRAS proto-oncogene, GTPase Homo sapiens 236-240 26125448-3 2015 RESULTS: In patients receiving selumetinib+docetaxel and harbouring KRAS G12C or G12V mutations there were trends towards greater improvement in OS, PFS and ORR compared with other KRAS mutations. AZD 6244 31-42 KRAS proto-oncogene, GTPase Homo sapiens 68-72 26125448-3 2015 RESULTS: In patients receiving selumetinib+docetaxel and harbouring KRAS G12C or G12V mutations there were trends towards greater improvement in OS, PFS and ORR compared with other KRAS mutations. AZD 6244 31-42 KRAS proto-oncogene, GTPase Homo sapiens 181-185 26125448-4 2015 CONCLUSION: Different KRAS mutations in NSCLC may influence selumetinib/docetaxel sensitivity. AZD 6244 60-71 KRAS proto-oncogene, GTPase Homo sapiens 22-26 25961376-3 2015 Here, we identified that Signal Transducer and Activator of Transcription 3 (STAT3) was significantly activated following the MEK inhibition using AZD6244, PD98059 and Trametinib in K-Ras mutant pancreatic and colon cancer cells. AZD 6244 147-154 KRAS proto-oncogene, GTPase Homo sapiens 182-187 25667274-3 2015 Patients were enrolled onto a not-otherwise-specified arm and treated with standard-of-care therapies or one of the following five biomarker-matched treatment groups: erlotinib for EGFR mutations; selumetinib for KRAS, NRAS, HRAS, or BRAF mutations; MK2206 for PIK3CA, AKT, or PTEN mutations; lapatinib for ERBB2 mutations or amplifications; and sunitinib for KIT or PDGFRA mutations or amplification. AZD 6244 197-208 KRAS proto-oncogene, GTPase Homo sapiens 213-217 25516890-2 2015 KRAS-mutant cells may exhibit resistance to the allosteric MEK1/2 inhibitor selumetinib (AZD6244; ARRY-142886) and allosteric AKT inhibitors (such as MK-2206), the combination of which may overcome resistance to both monotherapies. AZD 6244 76-87 KRAS proto-oncogene, GTPase Homo sapiens 0-4 25516890-2 2015 KRAS-mutant cells may exhibit resistance to the allosteric MEK1/2 inhibitor selumetinib (AZD6244; ARRY-142886) and allosteric AKT inhibitors (such as MK-2206), the combination of which may overcome resistance to both monotherapies. AZD 6244 89-96 KRAS proto-oncogene, GTPase Homo sapiens 0-4 25342139-0 2015 BYL719, a selective inhibitor of phosphoinositide 3-Kinase alpha, enhances the effect of selumetinib (AZD6244, ARRY-142886) in KRAS-mutant non-small cell lung cancer. AZD 6244 89-100 KRAS proto-oncogene, GTPase Homo sapiens 127-131 25342139-0 2015 BYL719, a selective inhibitor of phosphoinositide 3-Kinase alpha, enhances the effect of selumetinib (AZD6244, ARRY-142886) in KRAS-mutant non-small cell lung cancer. AZD 6244 102-109 KRAS proto-oncogene, GTPase Homo sapiens 127-131 25342139-7 2015 RESULTS: The combination of BYL719 and selumetinib resulted in synergistic cytotoxic activity compared with the single agents alone in KRAS-mutant NSCLC cells. AZD 6244 39-50 KRAS proto-oncogene, GTPase Homo sapiens 135-139 26567773-4 2015 For absence of NRAS, KRAS and BRAF mutation, SGC7901 and BGC823 gastric cancer cells were relative resistance to AZD6244 in vitro. AZD 6244 113-120 KRAS proto-oncogene, GTPase Homo sapiens 21-25 25342139-8 2015 At the molecular level, we found that AKT activation strongly influenced the sensitivity of KRAS-mutant NSCLC cells to selumetinib. AZD 6244 119-130 KRAS proto-oncogene, GTPase Homo sapiens 92-96 25342139-9 2015 Selumetinib upregulated phospho-AKT and phosphorylated BAD at ser136, which is responsible for intrinsic drug resistance in KRAS-mutant NSCLC cells. AZD 6244 0-11 KRAS proto-oncogene, GTPase Homo sapiens 124-128 24935174-6 2014 KRAS amplification was associated with worse clinical outcomes, and the KRAS gene mutation predicted sensitivity to the MEK1/2 inhibitor AZD6244 in gastric cancer cell lines. AZD 6244 137-144 KRAS proto-oncogene, GTPase Homo sapiens 72-76 25385055-7 2015 Expert opinion: Given the frequency of activated MAPK signaling in multiple tumor types, the potent MEK inhibitor selumetinib had strong preclinical and early clinical rationale, particularly in those tumors harboring KRAS or BRAF mutations. AZD 6244 114-125 KRAS proto-oncogene, GTPase Homo sapiens 218-222 24716986-9 2014 CONCLUSIONS: Compared with current chemotherapy, selumetinib has modest clinical activity as monotherapy in patients with advanced cancer, but combinations of selumetinib with cytotoxic agents in patients with BRAF or KRAS mutations hold great promise for cancer treatment. AZD 6244 159-170 KRAS proto-oncogene, GTPase Homo sapiens 218-222 24406751-6 2014 Selumetinib added to docetaxel has improved outcome compared with docetaxel in a randomized phase II trial in patients with advanced KRAS-mutant NSCLC and this combination is currently studied in a phase III trial. AZD 6244 0-11 KRAS proto-oncogene, GTPase Homo sapiens 133-137 25342991-4 2014 For patients with KRAS mutant NSCLC, a phase III trial of the MEK inhibitor, selumetinib, has been initiated. AZD 6244 77-88 KRAS proto-oncogene, GTPase Homo sapiens 18-22 21674991-8 2011 Knockdown of KRAS reversed AZD6244 resistance in HCT116 cells as well as reduced the activation of ERK1/2 and protein kinase B; however, the combined inhibition of ERK1/2 and phosphatidylinositol 3-kinase signaling had little effect on AZD6244 resistance, suggesting that additional KRAS effector pathways contribute to this process. AZD 6244 236-243 KRAS proto-oncogene, GTPase Homo sapiens 13-17 23414467-0 2013 Selumetinib: a promising pharmacologic approach for KRAS-mutant advanced non-small-cell lung cancer. AZD 6244 0-11 KRAS proto-oncogene, GTPase Homo sapiens 52-56 23414467-4 2013 Importantly, as a MEK inhibitor, selumetinib could be particularly effective in tumors with a hyperactivated Ras/Raf/MEK/ERK pathway, which might be the case of KRAS-mutant non-small-cell lung cancers (NSCLCs). AZD 6244 33-44 KRAS proto-oncogene, GTPase Homo sapiens 161-165 23414467-5 2013 Accordingly, a recent randomized Phase II study evaluating docetaxel plus selumetinib or placebo in KRAS-mutant pretreated advanced NSCLC patients has demonstrated a significant improvement in terms of response rate, progression-free survival and patient-reported outcomes in favor of the combination arm. AZD 6244 74-85 KRAS proto-oncogene, GTPase Homo sapiens 100-104 22082529-1 2012 Previously, we found that KRAS mutant cancer cells showed variable response to AZD6244, a MEK inhibitor through differential activation of EGFR/AKT. AZD 6244 79-86 KRAS proto-oncogene, GTPase Homo sapiens 26-30 22173548-4 2012 The activity of selumetinib and vorinostat against the KRAS-mutant SW620 and SW480 CRC cell lines was studied in vitro and in vivo. AZD 6244 16-27 KRAS proto-oncogene, GTPase Homo sapiens 55-59 22173548-11 2012 CONCLUSION: These data indicate that the rationally based combination of the mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor, selumetinib, with the HDAC inhibitor vorinostat results in synergistic antiproliferative activity against KRAS-mutant CRC cell lines in vitro. AZD 6244 159-170 KRAS proto-oncogene, GTPase Homo sapiens 265-269 21385921-8 2011 Combination treatments of erlotinib and two MAP kinase kinase (MEK) inhibitors, RDEA119 and AZD6244, showed significant synergistic effect for both combinations (RDEA119-erlotinib and AZD6244-erlotinib) compared with the corresponding single drug treatments in pancreatic cancer cell lines with wild-type KRAS (BxPC-3 and Hs 700T) but not in cell lines with mutant KRAS (MIA PaCa-2 and PANC-1). AZD 6244 92-99 KRAS proto-oncogene, GTPase Homo sapiens 305-309 21385921-8 2011 Combination treatments of erlotinib and two MAP kinase kinase (MEK) inhibitors, RDEA119 and AZD6244, showed significant synergistic effect for both combinations (RDEA119-erlotinib and AZD6244-erlotinib) compared with the corresponding single drug treatments in pancreatic cancer cell lines with wild-type KRAS (BxPC-3 and Hs 700T) but not in cell lines with mutant KRAS (MIA PaCa-2 and PANC-1). AZD 6244 92-99 KRAS proto-oncogene, GTPase Homo sapiens 365-369 21385921-8 2011 Combination treatments of erlotinib and two MAP kinase kinase (MEK) inhibitors, RDEA119 and AZD6244, showed significant synergistic effect for both combinations (RDEA119-erlotinib and AZD6244-erlotinib) compared with the corresponding single drug treatments in pancreatic cancer cell lines with wild-type KRAS (BxPC-3 and Hs 700T) but not in cell lines with mutant KRAS (MIA PaCa-2 and PANC-1). AZD 6244 184-191 KRAS proto-oncogene, GTPase Homo sapiens 305-309 21385921-8 2011 Combination treatments of erlotinib and two MAP kinase kinase (MEK) inhibitors, RDEA119 and AZD6244, showed significant synergistic effect for both combinations (RDEA119-erlotinib and AZD6244-erlotinib) compared with the corresponding single drug treatments in pancreatic cancer cell lines with wild-type KRAS (BxPC-3 and Hs 700T) but not in cell lines with mutant KRAS (MIA PaCa-2 and PANC-1). AZD 6244 184-191 KRAS proto-oncogene, GTPase Homo sapiens 365-369 21118963-7 2011 Inhibition of MEK by AS703026 or AZD6244 also suppressed cetuximab-resistant colorectal cancer cells attributed to K-ras mutation both in vitro and in vivo. AZD 6244 33-40 KRAS proto-oncogene, GTPase Homo sapiens 115-120 24130864-7 2013 While BxPC-3 (KRAS wild type) and MIA PaCa-2 (KRAS mutated) cell lines were sensitive to GDC0941 and AZD6244 as single agents, synergistic inhibition of tumor cell growth and induction of apoptosis were observed in both cell lines when the two drugs were combined. AZD 6244 101-108 KRAS proto-oncogene, GTPase Homo sapiens 14-18 24130864-7 2013 While BxPC-3 (KRAS wild type) and MIA PaCa-2 (KRAS mutated) cell lines were sensitive to GDC0941 and AZD6244 as single agents, synergistic inhibition of tumor cell growth and induction of apoptosis were observed in both cell lines when the two drugs were combined. AZD 6244 101-108 KRAS proto-oncogene, GTPase Homo sapiens 46-50 24063423-0 2013 Selumetinib in advanced non small cell lung cancer (NSCLC) harbouring KRAS mutation: endless clinical challenge to KRAS-mutant NSCLC. AZD 6244 0-11 KRAS proto-oncogene, GTPase Homo sapiens 70-74 24063423-0 2013 Selumetinib in advanced non small cell lung cancer (NSCLC) harbouring KRAS mutation: endless clinical challenge to KRAS-mutant NSCLC. AZD 6244 0-11 KRAS proto-oncogene, GTPase Homo sapiens 115-119 24063423-8 2013 Selumetinib (AZD6244; ARRY-142886) is an oral, tight-binding, uncompetitive inhibitor of mitogen-activated protein kinase kinases (MEK) 1 and 2, downstream of KRAS, with preclinical evidence of synergistic activity with docetaxel in KRAS-mutant cancers and currently in clinical development. AZD 6244 0-11 KRAS proto-oncogene, GTPase Homo sapiens 159-163 24063423-8 2013 Selumetinib (AZD6244; ARRY-142886) is an oral, tight-binding, uncompetitive inhibitor of mitogen-activated protein kinase kinases (MEK) 1 and 2, downstream of KRAS, with preclinical evidence of synergistic activity with docetaxel in KRAS-mutant cancers and currently in clinical development. AZD 6244 0-11 KRAS proto-oncogene, GTPase Homo sapiens 233-237 24063423-8 2013 Selumetinib (AZD6244; ARRY-142886) is an oral, tight-binding, uncompetitive inhibitor of mitogen-activated protein kinase kinases (MEK) 1 and 2, downstream of KRAS, with preclinical evidence of synergistic activity with docetaxel in KRAS-mutant cancers and currently in clinical development. AZD 6244 13-20 KRAS proto-oncogene, GTPase Homo sapiens 159-163 24063423-8 2013 Selumetinib (AZD6244; ARRY-142886) is an oral, tight-binding, uncompetitive inhibitor of mitogen-activated protein kinase kinases (MEK) 1 and 2, downstream of KRAS, with preclinical evidence of synergistic activity with docetaxel in KRAS-mutant cancers and currently in clinical development. AZD 6244 13-20 KRAS proto-oncogene, GTPase Homo sapiens 233-237 24063423-10 2013 Recently, in a randomised, phase II trial selumetinib plus docetaxel has proven to improve progression free survival compared to docetaxel alone in previously treated patients with advanced KRAS-mutant NSCLC. AZD 6244 42-53 KRAS proto-oncogene, GTPase Homo sapiens 190-194 23200175-0 2013 Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study. AZD 6244 0-11 KRAS proto-oncogene, GTPase Homo sapiens 31-35 23200175-2 2013 Selumetinib is an inhibitor of MEK1/MEK2, downstream of KRAS, with preclinical evidence of synergistic activity with docetaxel in KRAS-mutant cancers. AZD 6244 0-11 KRAS proto-oncogene, GTPase Homo sapiens 56-60 23200175-2 2013 Selumetinib is an inhibitor of MEK1/MEK2, downstream of KRAS, with preclinical evidence of synergistic activity with docetaxel in KRAS-mutant cancers. AZD 6244 0-11 KRAS proto-oncogene, GTPase Homo sapiens 130-134 23200175-3 2013 We did a prospective, randomised, phase 2 trial to assess selumetinib plus docetaxel in previously treated patients with advanced KRAS-mutant NSCLC. AZD 6244 58-69 KRAS proto-oncogene, GTPase Homo sapiens 130-134 23200175-16 2013 INTERPRETATION: Selumetinib plus docetaxel has promising efficacy, albeit with a higher number of adverse events than with docetaxel alone, in previously treated advanced KRAS-mutant NSCLC. AZD 6244 16-27 KRAS proto-oncogene, GTPase Homo sapiens 171-175 23200175-17 2013 These findings warrant further clinical investigation of selumetinib plus docetaxel in KRAS-mutant NSCLC. AZD 6244 57-68 KRAS proto-oncogene, GTPase Homo sapiens 87-91 21447798-2 2011 We modeled acquired resistance to the MEK1/2 (mitogen-activated or extracellular signal-regulated protein kinase kinases 1 and 2) inhibitor selumetinib (AZD6244) in colorectal cancer cell lines harboring mutations in BRAF (COLO205 and HT29 lines) or KRAS (HCT116 and LoVo lines). AZD 6244 140-151 KRAS proto-oncogene, GTPase Homo sapiens 250-254 21447798-7 2011 Knockdown of KRAS reversed AZD6244 resistance in HCT116 cells as well as reduced the activation of ERK1/2 and protein kinase B; however, the combined inhibition of ERK1/2 and phosphatidylinositol 3-kinase signaling had little effect on AZD6244 resistance, suggesting that additional KRAS effector pathways contribute to this process. AZD 6244 27-34 KRAS proto-oncogene, GTPase Homo sapiens 13-17 21447798-7 2011 Knockdown of KRAS reversed AZD6244 resistance in HCT116 cells as well as reduced the activation of ERK1/2 and protein kinase B; however, the combined inhibition of ERK1/2 and phosphatidylinositol 3-kinase signaling had little effect on AZD6244 resistance, suggesting that additional KRAS effector pathways contribute to this process. AZD 6244 236-243 KRAS proto-oncogene, GTPase Homo sapiens 13-17 21118963-0 2011 MEK1/2 inhibitors AS703026 and AZD6244 may be potential therapies for KRAS mutated colorectal cancer that is resistant to EGFR monoclonal antibody therapy. AZD 6244 31-38 KRAS proto-oncogene, GTPase Homo sapiens 70-74 21118963-3 2011 In this study, we investigated the ability of two MEK inhibitors currently in clinical trials, AS703026 and AZD6244, to address the challenge posed by the resistance of K-ras mutated colorectal cancers to EGFR mAb. AZD 6244 108-115 KRAS proto-oncogene, GTPase Homo sapiens 169-174 21674991-3 2011 We modeled acquired resistance to the MEK1/2 (mitogen-activated or extracellular signal-regulated protein kinase kinases 1 and 2) inhibitor selumetinib (AZD6244) in colorectal cancer cell lines harboring mutations in BRAF (COLO205 and HT29 lines) or KRAS (HCT116 and LoVo lines). AZD 6244 140-151 KRAS proto-oncogene, GTPase Homo sapiens 250-254 21674991-8 2011 Knockdown of KRAS reversed AZD6244 resistance in HCT116 cells as well as reduced the activation of ERK1/2 and protein kinase B; however, the combined inhibition of ERK1/2 and phosphatidylinositol 3-kinase signaling had little effect on AZD6244 resistance, suggesting that additional KRAS effector pathways contribute to this process. AZD 6244 27-34 KRAS proto-oncogene, GTPase Homo sapiens 13-17 20923857-0 2010 Identification of predictive markers of response to the MEK1/2 inhibitor selumetinib (AZD6244) in K-ras-mutated colorectal cancer. AZD 6244 73-84 KRAS proto-oncogene, GTPase Homo sapiens 98-103 20923857-0 2010 Identification of predictive markers of response to the MEK1/2 inhibitor selumetinib (AZD6244) in K-ras-mutated colorectal cancer. AZD 6244 86-93 KRAS proto-oncogene, GTPase Homo sapiens 98-103 20923857-9 2010 Baseline gene array data from CRC cell lines and xenografts were used to develop a k-top scoring pair (k-TSP) classifier, which predicted with 71% accuracy which of a test set of patient-derived K-ras mutant CRC explants would respond to AZD6244, providing the basis for a patient-selective clinical trial. AZD 6244 238-245 KRAS proto-oncogene, GTPase Homo sapiens 195-200 19637312-8 2009 We conclude that AZD6244 is effective in colorectal cancer cell lines with BRAF or KRAS mutations. AZD 6244 17-24 KRAS proto-oncogene, GTPase Homo sapiens 83-87 19637312-9 2009 Sensitivity to MEK1/2 inhibition correlates with a biochemical signature; those cells with high ERK1/2 activity (whether mutant for BRAF or KRAS) evolve a dependency upon that pathway and tend to be sensitive to AZD6244 but this can be offset by high PI3K-dependent signalling. AZD 6244 212-219 KRAS proto-oncogene, GTPase Homo sapiens 140-144 18676837-5 2008 In the majority of cell lines tested, including those with K-ras or non-V600E BRAF mutations, AZD6244 induced the accumulation of phospho-MEK, an effect not observed in the most sensitive BRAF V600E-containing cells. AZD 6244 94-101 KRAS proto-oncogene, GTPase Homo sapiens 59-64