|
Malignant Neoplasms
|
0.400 |
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 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
We evaluated the safety and efficacy of the MEK 1/2 inhibitor binimetinib in advanced myeloid malignancies.
|
30635233 |
2019 |
|
Malignant Neoplasms
|
0.400 |
GeneticVariation
|
group |
BEFREE |
This review discussed the function of MEK1 mutations, retrieved the frequency and distribution of MEK1 mutations in various malignancies, and reviewed the basic experiments and clinical case reports on trametinib in the treatment of cell lines or patients with MEK1 mutations.
|
31715422 |
2019 |
|
Malignant Neoplasms
|
0.400 |
GeneticVariation
|
group |
BEFREE |
Utility of targeting the MAPK pathway has been demonstrated by clinical responses to inhibitors of MEK1/2 or RAF kinases in some mutant BRAF-activated malignancies.
|
30275173 |
2019 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Consequently, MEK1 has attracted much interest as a target for cancer therapy to block the aberrant activity.
|
29753091 |
2019 |
|
Malignant Neoplasms
|
0.400 |
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 |
|
Malignant Neoplasms
|
0.400 |
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 |
|
Malignant Neoplasms
|
0.400 |
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 |
|
Malignant Neoplasms
|
0.400 |
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 |
|
Malignant Neoplasms
|
0.400 |
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 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
MEK1/2 MAPK kinases are very important for cancer survival and development.
|
28178630 |
2017 |
|
Malignant Neoplasms
|
0.400 |
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 |
|
Malignant Neoplasms
|
0.400 |
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 |
|
Malignant Neoplasms
|
0.400 |
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 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Selumetinib is an allosteric, ATP-noncompetitive inhibitor of MEK1/2, which has benn known as effective antineoplastic drugs for several malignant tumors.
|
27769200 |
2016 |
|
Malignant Neoplasms
|
0.400 |
AlteredExpression
|
group |
BEFREE |
AZD6244, an ATP-uncompetitive inhibitor of mitogen-activated protein kinase 1/2 (MEK1/2), has shown activity in several malignant tumours.
|
24375836 |
2014 |
|
Malignant Neoplasms
|
0.400 |
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 |
|
Malignant Neoplasms
|
0.400 |
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 |
|
Malignant Neoplasms
|
0.400 |
AlteredExpression
|
group |
BEFREE |
The targeted small-molecule drug AZD6244 is an allosteric, ATP-noncompetitive inhibitor of MEK1/2 that has shown activity against several malignant tumors.
|
24938872 |
2014 |
|
Malignant Neoplasms
|
0.400 |
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 |
|
Malignant Neoplasms
|
0.400 |
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 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
MEK1/2 inhibitors such as AZD6244 are in clinical trials for the treatment of multiple cancers, including breast cancer.
|
23530058 |
2013 |
|
Malignant Neoplasms
|
0.400 |
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 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Selumetinib is a potent and selective inhibitor of MEK1 and 2 that is currently being clinically developed for the treatment of several human malignancies.
|
23414467 |
2013 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
We therefore assessed the safety and activity of selumetinib, an inhibitor of MEK1/2, for patients with this cancer.
|
23261356 |
2013 |