PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33081092-4 2020 In our study, we investigated the MEK inhibitor selumetinib and PI3K/mTOR dual inhibitor BEZ235 alone and in combination in BRAF-only mutant and BRAF + PI3K/PTEN double mutant cancer cells using short- and long-term 2D viability assays, spheroid assays, and immunoblots. AZD 6244 48-59 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 145-149 35489723-9 2022 Lenvatinib and selumetinib decreases SREBP1 expression in the BRAF-mutant cell line BHT-101. AZD 6244 15-26 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 62-66 35250023-3 2022 The MEK1/2 Inhibitor AZD6244 Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib. AZD 6244 21-28 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 40-44 32880495-11 2020 There are several highly successful non-NSCLC selumetinib trials involving, e.g., patients with neurofibromatosis type 1 related tumors and children with low-grade BRAF-driven gliomas. AZD 6244 46-57 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 164-168 34831012-12 2021 The negative impact on NIS expression induced by the MAPK-activating alterations, NRAS Q61R and BRAF V600E, was partially reversed by the presence of the MEK 1/2 inhibitors AZD6244 and CH5126766. AZD 6244 173-180 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 96-100 33081092-5 2020 In the 2D assays, selumetinib was more effective on BRAF-only mutant lines when compared to BRAF + PI3K/PTEN double mutants. AZD 6244 18-29 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 52-56 31502118-9 2019 Treatment with selumetinib and trametinib, but not dabrafenib, restored the sensitivity to osimertinib and enhanced cell death in the resistant clones with the BRAF G469A mutation. AZD 6244 15-26 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 160-164 32181767-9 2020 Finally, in non-V600 BRAF mutant cell lines combined inhibition of pan-RAF and MEK with sorafenib/AZ628 and selumetinib showed significantly stronger cell growth, cell migration and Erk activation inhibition and also increased apoptosis induction compared to single treatments. AZD 6244 108-119 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 21-25 23847359-1 2013 Selumetinib plus dacarbazine prolongs progression-free survival in BRAF-mutant melanoma. AZD 6244 0-11 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 67-71 30579838-0 2019 Schedule-dependent synergistic effects of 5-fluorouracil and selumetinib in KRAS or BRAF mutant colon cancer models. AZD 6244 61-72 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 84-88 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 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 134-138 27813079-5 2017 The MEK inhibitor selumetinib-similarly to that of the BRAF-specific inhibitor-also increases PMCA4b levels in both BRAF and NRAS mutant melanoma cells suggesting that the MAPK pathway is involved in the regulation of PMCA4b expression. AZD 6244 18-29 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 116-120 26672083-2 2015 Although selumetinib did not improve survival or response, most responders had BRAF-activating mutations, and selumetinib has since demonstrated efficacy in BRAF-mutant melanoma. AZD 6244 110-121 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 157-161 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 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 30-34 25981859-6 2015 RESULTS: Inhibition of MEK signaling by selumetinib suppressed TORC1 signaling only in the context of the BRAF-mutant both in vitro and in vivo. AZD 6244 40-51 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 106-110 25981859-8 2015 CONCLUSIONS: Selumetinib suppressed TORC1 signaling in the context of BRAF mutation. AZD 6244 13-24 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 70-74 25297634-2 2014 We found that a subset of BRAF- and NRAS-mutant human melanomas resistant to the MEK inhibitor selumetinib displayed increased oxidative phosphorylation (OxPhos) mediated by the transcriptional coactivator PGC1alpha. AZD 6244 95-106 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 26-30 24567366-3 2014 The aim of this study was to assess the efficacy and safety of selumetinib plus docetaxel as first-line treatment in patients with wild-type BRAF advanced melanoma. AZD 6244 63-74 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 141-145 24200969-7 2014 Further analysis of 46 melanoma cell lines that harbored BRAF mutation showed that 7 pathways, including TNFalpha, EGFR, IFNalpha, hypoxia, IFNgamma, STAT3, and MYC, were significantly differently expressed in AZD6244-resistant compared with responsive melanoma cells. AZD 6244 210-217 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 57-61 24200969-8 2014 A SVM classifier built on this 7-pathway activation pattern correctly predicted the response of 10 BRAF-mutated melanoma cell lines to the MEK inhibitor AZD6244 in our experiments. AZD 6244 153-160 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 99-103 30847387-5 2019 However, MAPKi (dabrafenib or selumetinib) induced these effects only in BRAF V600E-mutant cells. AZD 6244 30-41 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 73-77 30847387-6 2019 Combined treatment with panobinostat and MAPKi (dabrafenib or selumetinib) displayed a more robust BRAF V600E-dependent redifferentiation effect than panobinostat alone via further improving the acetylation level of histone at the sodium-iodide symporter (NIS) promoter. AZD 6244 62-73 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 99-103 29737325-0 2018 The MEK1/2 Inhibitor AZD6244 Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib. AZD 6244 21-28 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 40-44 29040023-2 2017 We report a patient with disseminated LGG with the BRAFV600E mutation, which was refractory to selumetinib, a MEK inhibitor, but subsequently showed immediate clinical and radiographic response to dabrafenib, a BRAF inhibitor, with sustained effect for 9 months prior to clinical progression. AZD 6244 95-106 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 51-55 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 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 226-230 25199829-6 2014 MEK inhibition induces RAS activation and BRAF-RAF1 dimerization and sustains MEK-ERK signaling, which is responsible for intrinsic resistance to selumetinib. AZD 6244 146-157 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 42-46 23735514-0 2013 Selumetinib plus dacarbazine versus placebo plus dacarbazine as first-line treatment for BRAF-mutant metastatic melanoma: a phase 2 double-blind randomised study. AZD 6244 0-11 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 89-93 23735514-2 2013 Selumetinib, a MEK1/2 inhibitor, has shown antitumour activity in patients with BRAF-mutant melanoma and in preclinical models when combined with chemotherapy. AZD 6244 0-11 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 80-84 23735514-14 2013 INTERPRETATION: Selumetinib plus dacarbazine showed clinical activity in patients with BRAF-mutant cutaneous or unknown primary melanoma, reflected by a significant benefit in progression-free survival compared with placebo plus dacarbazine group, although no significant change in overall survival was noted. AZD 6244 16-27 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 87-91 23234544-7 2013 Finally, cancer cells in which acquired resistance to selumetinib arises through BRAF(V600E) amplification remained sensitive to ABT-263, whereas selumetinib-resistant HCT116 cells (KRAS(G13D) amplification) were cross-resistant to ABT-263. AZD 6244 54-65 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 81-86 23444215-1 2013 PURPOSE: Test the hypothesis that in BRAF-mutated melanomas, clinical responses to selumetinib, a MEK inhibitor, will be restricted to tumors in which the PI3K/AKT pathway is not activated. AZD 6244 83-94 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 37-41 22972589-2 2013 The authors hypothesized that the presence of BRAF or NRAS mutations would correlate with clinical benefit among patients who received treatment with combination regimens that included the MEK inhibitor selumetinib. AZD 6244 203-214 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 46-50 23406027-10 2013 Selumetinib increased the uptake of iodine-124 in 12 of the 20 patients (4 of 9 patients with BRAF mutations and 5 of 5 patients with NRAS mutations). AZD 6244 0-11 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 94-98 22972589-11 2013 CONCLUSIONS: Higher response rates and longer TTP were observed with selumetinib-containing regimens in patients who had tumors that harbored a BRAF mutation compared with patients who had wild-type BRAF. AZD 6244 69-80 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 144-148 22972589-11 2013 CONCLUSIONS: Higher response rates and longer TTP were observed with selumetinib-containing regimens in patients who had tumors that harbored a BRAF mutation compared with patients who had wild-type BRAF. AZD 6244 69-80 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 199-203 22895053-3 2012 As a follow-up to that study, treatment of BRAF-mutant and NRAS-mutant melanoma lines with WNT3A and the MEK inhibitor AZD6244 also induces apoptosis. AZD 6244 119-126 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 43-47 22895053-5 2012 Apoptosis-resistant NRAS-mutant lines can sensitize to AZD6244 by pretreatment with AXIN1 siRNA, similar to what we previously reported in BRAF-mutant cell lines. AZD 6244 55-62 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 139-143 22293660-0 2012 A prolonged complete response in a patient with BRAF-mutated melanoma stage IV treated with the MEK1/2 inhibitor selumetinib (AZD6244). AZD 6244 113-124 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 48-52 22293660-0 2012 A prolonged complete response in a patient with BRAF-mutated melanoma stage IV treated with the MEK1/2 inhibitor selumetinib (AZD6244). AZD 6244 126-133 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 48-52 21447798-6 2011 Inhibition of BRAF reversed resistance to AZD6244 in COLO205 cells, which suggested that combined inhibition of MEK1/2 and BRAF may reduce the likelihood of acquired resistance in tumors with BRAF(600E). AZD 6244 42-49 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 14-18 22394161-7 2012 The results of early clinical studies of selumetinib suggest that selumetinib may have a role in melanoma therapy, especially in certain subsets of patients, such as those whose tumor harbors a BRAF mutation. AZD 6244 66-77 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 194-198 21828154-5 2011 RESULTS: BRAF-mutant UM cells were sensitive to both PLX4720 and AZD6244, undergoing cell cycle arrest but not apoptosis. AZD 6244 65-72 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 9-13 21828154-8 2011 The combination of AZD6244 with PLX4720 had synergistic anticancer activity in BRAF-mutant cells but not in Galpha-mutant cells. AZD 6244 19-26 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 79-83 22451620-2 2012 Here, selumetinib targets the mitogen-activated protein kinase pathway in papillary thyroid carcinoma and shows limited single-agent activity in the patients with tumors that harbor the (V600E)BRAF mutation. AZD 6244 6-17 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 193-197 22048237-8 2012 However, five of the six selumetinib partial responders were BRAF mutated. AZD 6244 25-36 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 61-65 22048237-11 2012 Five of six patients with partial response to selumetinib had BRAF mutant tumors. AZD 6244 46-57 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 62-66 22808163-4 2012 While synergistic reductions in cell viability were observed with AZD8055/selumetinib in both BRAF and GNAQ mutant cell lines, apoptosis was preferentially induced in BRAF mutant cells only. AZD 6244 74-85 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 94-98 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 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 217-221 21447798-6 2011 Inhibition of BRAF reversed resistance to AZD6244 in COLO205 cells, which suggested that combined inhibition of MEK1/2 and BRAF may reduce the likelihood of acquired resistance in tumors with BRAF(600E). AZD 6244 42-49 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 123-127 21447798-6 2011 Inhibition of BRAF reversed resistance to AZD6244 in COLO205 cells, which suggested that combined inhibition of MEK1/2 and BRAF may reduce the likelihood of acquired resistance in tumors with BRAF(600E). AZD 6244 42-49 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 123-127 20959481-0 2010 Basal and treatment-induced activation of AKT mediates resistance to cell death by AZD6244 (ARRY-142886) in Braf-mutant human cutaneous melanoma cells. AZD 6244 83-90 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 108-112 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 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 217-221 21674991-7 2011 Inhibition of BRAF reversed resistance to AZD6244 in COLO205 cells, which suggested that combined inhibition of MEK1/2 and BRAF may reduce the likelihood of acquired resistance in tumors with BRAF600E. AZD 6244 42-49 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 14-18 21674991-7 2011 Inhibition of BRAF reversed resistance to AZD6244 in COLO205 cells, which suggested that combined inhibition of MEK1/2 and BRAF may reduce the likelihood of acquired resistance in tumors with BRAF600E. AZD 6244 42-49 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 123-127 21098728-3 2010 To identify potential mechanisms of acquired drug resistance, we generated clones resistant to the allosteric MEK inhibitor AZD6244 from two BRAF V600E mutant colorectal cancer cell lines that are highly sensitive to MEK or BRAF inhibition. AZD 6244 124-131 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 141-145 21098728-4 2010 These AZD6244-resistant (AR) clones, which exhibited cross-resistance to BRAF inhibitors, acquired resistance through amplification of the BRAF gene. AZD 6244 6-13 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 73-77 21098728-4 2010 These AZD6244-resistant (AR) clones, which exhibited cross-resistance to BRAF inhibitors, acquired resistance through amplification of the BRAF gene. AZD 6244 6-13 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 139-143 21098728-7 2010 In cell lines, BRAF amplification increased the abundance of phosphorylated MEK and impaired the ability of AZD6244 to inhibit ERK (extracellular signal-regulated kinase) phosphorylation. AZD 6244 108-115 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 15-19 21098728-8 2010 The ability of AZD6244 to inhibit ERK phosphorylation in AR cells was restored by treatment with a BRAF inhibitor at low concentrations that reduced the abundance of phosphorylated MEK to amounts observed in parental cells. AZD 6244 15-22 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 99-103 20959481-7 2010 RPPA characterization of the time-dependent changes in signaling pathways revealed that AZD6244 produced durable and potent inhibition of P-MAPK in sensitive and resistant Braf-mutant cell lines, but several resistant lines showed AZD6244-induced activation of AKT. AZD 6244 88-95 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 172-176 20959481-10 2010 These findings identify basal and treatment-induced regulation of the PI3K-AKT pathway as a critical regulator of AZD6244 sensitivity in Braf-mutant cutaneous melanoma cells and the novel regulation of PTEN expression by AZD6244 in sensitive cells, and suggest new combinatorial approaches for patients. AZD 6244 114-121 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 137-141 20802351-13 2010 Based on preclinical data and recent clinical observations, further development of AZD6244 in NSCLC should focus on BRAF or RAS mutation-positive patients and/or AZD6244-based combination regimens. AZD 6244 83-90 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 116-120 18381570-11 2008 AZD6244 was more potent at inhibiting growth of NPA (BRAF +) than Cal62 (KRAS +) xenografts. AZD 6244 0-7 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 53-57 20806365-13 2010 However, AZD6244 was highly active against BT-40 JPA xenografts that harbor constitutively activated BRAF, causing complete regressions. AZD 6244 9-16 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 101-105 19915144-8 2009 However, exposing BRAF-mutant melanoma cells to AZD6244 and PLX4720 in combination prevented emergence of resistant clones. AZD 6244 48-55 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 18-22 19861964-0 2009 Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study. AZD 6244 80-87 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 13-17 19637312-8 2009 We conclude that AZD6244 is effective in colorectal cancer cell lines with BRAF or KRAS mutations. AZD 6244 17-24 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 75-79 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 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 132-136 18676837-0 2008 BRAF V600E disrupts AZD6244-induced abrogation of negative feedback pathways between extracellular signal-regulated kinase and Raf proteins. AZD 6244 20-27 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 0-4 18676837-3 2008 AZD6244 induced G(0)-G(1) cell cycle arrest in sensitive cell lines that primarily included cells containing the BRAF V600E mutation. AZD 6244 0-7 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 113-117 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 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 78-82 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 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 188-192 18676837-9 2008 Specific suppression of endogenous BRAF V600E does not confer resistance to AZD6244 but enhances sensitivity to AZD6244. AZD 6244 112-119 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 35-39 17699718-4 2007 In vitro cell viability inhibition screening of a tumor cell line panel found that lines harboring BRAF or RAS mutations were more likely to be sensitive to AZD6244. AZD 6244 157-164 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 99-103 17878251-0 2007 Selective growth inhibition in BRAF mutant thyroid cancer by the mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244. AZD 6244 119-126 B-Raf proto-oncogene, serine/threonine kinase Homo sapiens 31-35