|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
Consequently, MEK1 has attracted much interest as a target for cancer therapy to block the aberrant activity.
|
29753091 |
2019 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
Mitogen-activated protein kinases (MEK 1/2) are central components of the RAS signalling pathway and are attractive targets for cancer therapy.
|
30944457 |
2019 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
This study shows the importance of functional characterization of mutant alleles in single oncogenes and identifies a new class of MEK1 mutants, insensitive to current MEK1 inhibitors but treatable with a new ATP-competitive inhibitor.<i>Cancer Discov; 8(5); 648-61.
|
29483135 |
2018 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
A new class of MEK1 mutants is shown here to be RAF-independent, resistant to allosteric MEK inhibitors, and yet sensitive to treatment with a new ATP-competitive MEK inhibitor.<i>Cancer Discov; 8(5); 534-6.
|
29716939 |
2018 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
Targeting this node may provide a promising avenue for treatment of colon cancers that have acquired resistance to targeted therapies.<b>Significance:</b> MEK1 inhibitor-resistant colorectal cancer relies on the scaffold and endosomal protein CEMIP to maintain ERK1/2 signaling and Myc-driven transcription.<i>Cancer Res; 78(16); 4533-48.©2018 AACR</i>.
|
29915160 |
2018 |
|
Primary malignant neoplasm
|
0.100 |
AlteredExpression
|
group |
BEFREE |
We discovered multiple mosaic-activating variants in 4 genes of the RAS/MAPK pathway, KRAS, NRAS, BRAF, and MAP2K1, a pathway commonly activated in cancer and responsible for the germline RAS-opathies.
|
29461977 |
2018 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
In this issue of <i>Science Signaling</i>, Yuan <i>et al.</i> report that MEK1 homodimerization is necessary for signal transduction through the RAF-ERK pathway and that cancer-related MEK1 mutations confer enhanced dimerization and resistance to MEK inhibitors.
|
30377222 |
2018 |
|
Primary malignant neoplasm
|
0.100 |
AlteredExpression
|
group |
BEFREE |
The computational analysis suggested inhibitory effect due to bursehernin towards proteins related to cancer proliferation, including FMS kinase receptor, heat shock protein 90-α (Hsp90-α), adenylate cyclase 10 (ADCY10), mitogen-activated protein kinase kinase (MEK1), and α-tubulin.
|
28456097 |
2017 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
MEK1/2 MAPK kinases are very important for cancer survival and development.
|
28178630 |
2017 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
Using an RNAi-based screen targeting the majority of the known metabolic proteins, we recently found that oncogenic BRAF<sup>V600E</sup> up-regulates HMG-CoA lyase (HMGCL), which converts HMG-CoA to acetyl-CoA and a ketone body, acetoacetate, that selectively enhances BRAF<sup>V600E</sup>-dependent MEK1 activation in human cancer.
|
28468827 |
2017 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
We investigated receptor tyrosine kinase (RTK) alterations and MAP2K1 (MEK1) mutations in a large cohort of colorectal carcinoma patients studied by Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets and The Cancer Genome Atlas, focusing on amplifications, fusions, and hotspot mutations in RTK genes and MAP2K1.
|
26660078 |
2016 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
Their anticancer mechanisms of action, after binding to specific receptors on cancer cells, include targeting the Rat sarcoma-bound guanosine triphosphate (RAS) (95% inhibition)-mitogen activated protein kinase kinase 1/2 (MEK-1/2) (98% inhibition)-extracellular signal-related kinases 1/2 (ERK-1/2) (96% inhibition) cascade in cancer cells.They also inhibit MAPK9, i.e. c-JUN-N-terminal kinase 2.
|
24692673 |
2014 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
BRAF(V600E) phosphorylates and activates the MEK1 and MEK2 kinases, which in turn phosphorylate and activate the ERK1 and ERK2 kinases, stimulating the mitogen-activated protein kinase (MAPK) pathway to promote cancer.
|
24717435 |
2014 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
Therefore, PI3K inhibitor LY294002 (LY) and MEK1/2 inhibitor PD98059 (PD) are used to sensitize many types of cancer cell lines to chemotherapeutic agents, where AKT and ERK pathways are over activated.
|
23948751 |
2013 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
Furthermore, recently identified ERK1/2-inducing mutations in MEK1 and MEK2 (MEK1/2) MAPK genes in melanoma confer resistance to emerging therapeutic MEK inhibitors, underscoring the challenges facing direct kinase inhibition in cancer.
|
23603816 |
2013 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
We therefore assessed the safety and activity of selumetinib, an inhibitor of MEK1/2, for patients with this cancer.
|
23261356 |
2013 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
Taken together, these results reveal how MEK1/2 inhibition affects cancer cell metabolism in the context of BRAF oncogene addiction.
|
23639941 |
2013 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
In this issue of Cancer Discovery, Shi and colleagues add further insight into the role of exon 3 MEK1 mutations in BRAF inhibitor resistance by demonstrating the presence of P124SMEK1 and I111SMEK1 mutations concurrently with V600E/KBRAF mutations at baseline in 16% of melanoma specimens.
|
22588873 |
2012 |
|
Primary malignant neoplasm
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Given the addiction of cancer cells to the elevated MAP2K1 activity for proliferation, human cancers with such MAP2K1 mutations are suitable targets for the treatment with MAP2K1 inhibitors.
|
22327936 |
2012 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
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 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
Small-molecule inhibitors of MEK1/MEK2 are therefore viewed as attractive drug candidates for the targeted therapy of this malignancy.
|
19014680 |
2008 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
Response and determinants of cancer cell susceptibility to PI3K inhibitors: combined targeting of PI3K and Mek1 as an effective anticancer strategy.
|
18059185 |
2008 |
|
Primary malignant neoplasm
|
0.100 |
AlteredExpression
|
group |
BEFREE |
However, the role of MAPK kinases (MAPKKs or MEKs) in cancer is unclear, although constitutively activated MEK1, which does not exist in nature, is "oncogenic."
|
17631144 |
2007 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
In this study, we report novel BRAF mutations in exon 4 and exon 12 and also report the first mutation in MEK1 associated with human cancer.
|
18060073 |
2007 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
Gene expressions of CC3 and MEK1 were recognized to be induced by heat-shock in pharyngeal cancer cells (KB, T3M-1) and lingual cancer cells (SCC-TF).
|
12007959 |
2002 |