Non-Small Cell Lung Carcinoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
As a proof of concept, we applied this approach to a KRAS-dependent non-small cell lung cancer (NSCLC) cell line, H23-KRAS<sup>G12C</sup> Using a combination of phenotypic screens, signaling analyses, and kinase inhibitors, we found that dual inhibition of MEK1/2 and insulin-like growth factor 1 receptor (IGF1R)/insulin receptor (INSR) is critical for blocking proliferation in cells.
|
30858179 |
2019 |
Non-Small Cell Lung Carcinoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Selumetinib (AZD6244, ARRY142886), a MEK1/2 inhibitor combined with chemotherapy in patients with NSCLC was evaluated in two schedules to evaluate efficacy and toxicity.
|
31200828 |
2019 |
Non-Small Cell Lung Carcinoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Further research aimed at discovering biomarkers of response and resistance to MEK1/2 inhibitors will be needed to develop rational combination strategies for the treatment of NSCLC driven by aberrant MAPK signaling.
|
29216787 |
2018 |
Non-Small Cell Lung Carcinoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Aldehyde Dehydrogenase 1 (ALDH1) Promotes the Toxicity of TRAIL in Non-Small Cell Lung Cancer Cells via Post-Transcriptional Regulation of MEK-1 Expression.
|
30448845 |
2018 |
Non-Small Cell Lung Carcinoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
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.
|
27467210 |
2016 |
Non-Small Cell Lung Carcinoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
In a recent phase II study, selumetinib (AZD6244, ARRY-142886), an oral, potent and selective, allosteric MEK1/2 inhibitor with a short half-life, combined with docetaxel, improved clinical outcome as second-line treatment for patients with KRASm NSCLC.
|
26837474 |
2016 |
Non-Small Cell Lung Carcinoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
According to the current knowledge, the incidence of MEK1 gene mutation in CNS metastatic lesion of NSCLC is the first such report worldwide.
|
26860843 |
2016 |
Non-Small Cell Lung Carcinoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC)†.
|
25722381 |
2015 |
Non-Small Cell Lung Carcinoma
|
0.500 |
CausalMutation
|
disease |
CLINVAR |
Prospective enterprise-level molecular genotyping of a cohort of cancer patients.
|
25157968 |
2014 |
Non-Small Cell Lung Carcinoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
With 8 μg of tumor aspirates, we precisely quantified the response of 18 signaling molecules to erlotinib and MEK1 inhibitor treatments in an NSCLC patient.
|
23979919 |
2013 |
Non-Small Cell Lung Carcinoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
EML4-ALK, PIK3CA, and MEK1 mutations occurred in NSCLC with various distinct clinicopathological characteristics.
|
23277484 |
2013 |
Non-Small Cell Lung Carcinoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Here, we identified a novel MEK1/2 inhibitor, CZ0775, and compared its cytotoxic effects to those of AZD6244 (selumetinib) in non-small cell lung cancer (NSCLC) cell lines harboring EGFR mutations.
|
24068620 |
2013 |
Non-Small Cell Lung Carcinoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Exposure of human NSCLC cell lines H1975 and H1650 to curcumin decreased MMC-elicited phosphorylated MKK1/2-ERK1/2 protein levels.
|
21973306 |
2012 |
Non-Small Cell Lung Carcinoma
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
We found that (1) H358, LC2, and H1975 cell lines highly expressed NAMPT-mRNA; (2) NAMPT-specific siRNA and FK866 suppressed proliferation of these NSCLCs; (3) FK866 reduced intracellular ATP levels in H1975 cells; (4) FK866 dephosphorylated EGFR signal proteins, including EGFR, Akt, Map kinase kinase 1/2, and extracellular signal-regulated kinase 1/2 (ERK 1/2); (5) FK866 induced apoptosis of H1975 cells; and (6) FK866 suppressed growth of H1975 xenograft tumors and attenuated expression of phospho-ERK 1/2 in the tumors in a tumor-bearing mouse model.
|
22089115 |
2012 |
Non-Small Cell Lung Carcinoma
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
Exposure of two human non-small lung cancer (NSCLC) cell lines (A549 and H1975) to curcumin could suppress MMC-induced MKK1/2-ERK1/2 signal activation and Rad51 protein expression.
|
21810436 |
2011 |
Non-Small Cell Lung Carcinoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
We investigated the MEK1 mutation (n = 280) and AKT2 mutation (n = 273) in surgically treated non-small cell lung cancer cases.
|
20354455 |
2010 |
Non-Small Cell Lung Carcinoma
|
0.500 |
CausalMutation
|
disease |
CLINVAR |
Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma.
|
18632602 |
2008 |
Non-Small Cell Lung Carcinoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
We also screened 85 NSCLC cell lines for MEK1 exon 2 mutations; one line (NCI-H1437) harbors a Q56P substitution, a known transformation-competent allele of MEK1 originally identified in rat fibroblasts, and is sensitive to treatment with AZD6244.
|
18632602 |
2008 |
Non-Small Cell Lung Carcinoma
|
0.500 |
CausalMutation
|
disease |
CLINVAR |
Mutation analysis of BRAF, MEK1 and MEK2 in 15 ovarian cancer cell lines: implications for therapy.
|
18060073 |
2007 |
Non-Small Cell Lung Carcinoma
|
0.500 |
CausalMutation
|
disease |
CLINVAR |
RAS signalling is abnormal in a c-raf1 MEK1 double mutant.
|
7651428 |
1995 |
Non-Small Cell Lung Carcinoma
|
0.500 |
CausalMutation
|
disease |
CGI |
|
|
|