|
Colorectal Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
MEK inhibitor enhanced the antitumor effect of oxaliplatin and 5‑fluorouracil in MEK1 Q56P‑mutant colorectal cancer cells.
|
30535504 |
2019 |
|
Colorectal Carcinoma
|
0.100 |
Biomarker
|
disease |
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></i>.
|
29915160 |
2018 |
|
Colorectal Carcinoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
CRC tumors in AA patients also appeared to harbor more mutations of mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1), MPL proto-oncogene (MPL), thrombo-poietin receptor, and neurofibromin 1 (NF1) than those from CC patients.
|
29599344 |
2018 |
|
Colorectal Carcinoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Wild-type and mutant KRAS/BRAF human CRC cell lines were treated with escalating doses of 5-FU or trifluridine with MEK162 (MEK1/2 inhibitor) for 72 h. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and synergism expressed by the combination index was calculated using CalcuSyn.
|
28551618 |
2017 |
|
Colorectal Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
The RNF183-IL-8 axis is responsible for the resistance of CRC cells to the MEK1/2 inhibitor trametinib and may serve as a candidate target for combined therapy for CRC.
|
28756770 |
2017 |
|
Colorectal Carcinoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
MAP2K1-mutated colorectal carcinoma showed no RAS/RAF mutations.
|
26660078 |
2016 |
|
Colorectal Carcinoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Rare mutations not typically associated with CRC included AKT1 (4), AKT2 (1), IDH1 (1), KIT (1), MAP2K1 (1), PTEN (2), and GNAS (6).
|
25683705 |
2015 |
|
Colorectal Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
In addition, the efficacy of OSI-906 combined with the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886) was evaluated in vivo using human colorectal cancer xenograft models.
|
24045180 |
2013 |
|
Colorectal Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Current MEK1-directed pharmacological strategies could thus be exploited, in combination with p38α inhibition, to develop new approaches for CRC treatment.
|
22579651 |
2012 |
|
Colorectal Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
We evaluated the antitumor activity of selumetinib (AZD6244, ARRY-142886), a potent and selective MEK1/2 inhibitor, on a panel of colorectal carcinoma (CRC) cells and found no inhibition of KRAS mutant CRC cell anchorage-independent growth.
|
21199803 |
2011 |
|
Colorectal Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
MEK1/2 inhibitors AS703026 and AZD6244 may be potential therapies for KRAS mutated colorectal cancer that is resistant to EGFR monoclonal antibody therapy.
|
21118963 |
2011 |
|
Colorectal Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Collectively, our findings indicate that oncogenic Kras regulates ADAM17 activity and thereby growth factor ligand shedding in a MEK1/2/Erk1/2-dependent manner and that KrasMT CRC tumors are vulnerable to MEK1/2 inhibitors, at least in part, due to their dependency on ADAM17 activity.
|
21148749 |
2011 |
|
Colorectal Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
The aim of this study was to develop and characterize predictive biomarkers of response to the MEK1/2 inhibitor AZD6244 in CRC in order to maximize the clinical utility of this agent.
|
20923857 |
2010 |
|
Colorectal Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
KRAS/BRAF mutation status and ERK1/2 activation as biomarkers for MEK1/2 inhibitor therapy in colorectal cancer.
|
19372556 |
2009 |
|
Colorectal Carcinoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
BIM is de-phosphorylated and upregulated following MEK1/2 inhibition in all CRC cell lines studied and knockdown of BIM reduces cell death, indicating that repression of BIM is a major part of the ability of BRAF(V600E) to confer growth factor-independent survival.
|
18806830 |
2008 |
|
Colorectal Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
However, the exact contribution of MEK1 and MEK2 to the pathogenesis of colorectal cancer remains to be established.
|
19014680 |
2008 |