Malignant neoplasm of colon and/or rectum
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Detection of the V600E hotspot mutation in BRAF oncogene is extremely useful for the screening of hereditary non-polyposis colorectal cancer (Lynch's syndrome) and for the prediction of sensitivity to MEK inhibitors.
|
18428050 |
2008 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
Oncogenic K-ras activates p38 to maintain colorectal cancer cell proliferation during MEK inhibition.
|
20413844 |
2010 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
Interestingly, combination of RTK and MEK inhibitors led to concomitant inhibition of PI3K and MEK signaling, marked growth suppression, and robust apoptosis of human KRAS mutant colorectal cancer cell lines in vitro and upon xenografting in mice.
|
21985784 |
2011 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Initial clinical results of MEK inhibitors have yielded limited single-agent activity in colorectal cancer, indicating that rational combination strategies are needed.
|
23757356 |
2013 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
Thymoquinone-induced conformational changes of PAK1 interrupt prosurvival MEK-ERK signaling in colorectal cancer.
|
25174975 |
2014 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer.
|
24576621 |
2014 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
Small interfering RNA (siRNA) screening of 37 KRAS mutant colorectal cancer cell lines showed that RAF1 suppression was synthetic lethal with MEK inhibition.
|
25199829 |
2014 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
ADAM17-dependent c-MET-STAT3 signaling mediates resistance to MEK inhibitors in KRAS mutant colorectal cancer.
|
24931611 |
2014 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
Furthermore, the combination of pan-RAF and MEK inhibitors displayed strong synergy in melanoma and colorectal cancer cell lines with RAS-activating events such as RTK activation, KRAS mutation, or NF1 loss-of-function mutations.
|
26351322 |
2015 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
HDAC Inhibition Overcomes Acute Resistance to MEK Inhibition in BRAF-Mutant Colorectal Cancer by Downregulation of c-FLIPL.
|
25813020 |
2015 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer.
|
26392102 |
2015 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
Finally, the positive correlation of RHBDD1 expression with the EGFR/Raf/MEK/ERK signalling pathway is further corroborated in a murine model of colitis-associated colorectal cancer.
|
26300397 |
2015 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
Combined inhibition of both MEK and CDK4/6 is effective in preclinical models of KRAS mutant CRC and justifies a planned phase II clinical trial in patients with refractory KRAS-mutant CRC.Efficacy of the combination of MEK and CDK4/6 inhibitors in vitro and in vivo in KRAS mutant colorectal cancer models.
|
27167191 |
2016 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
KRAS mutations have a significant role in the consecutive activation of RAS.RAF.MEK.ERK pathway in colorectal cancer.Approximately 30.35% of sporadic colorectal cancers have KRAS mutation.
|
27072218 |
2016 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
In this study, we determined that colorectal cancer progression specimens invariably harbored lesions in elements of the RAS-RAF-MEK-ERK pathway.
|
28951457 |
2017 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The response of BRAF mutant colorectal cancer to recent targeted strategies such as anti-BRAF or combinations with MEK and EGFR inhibitors remains limited and highly heterogeneous within BRAF V600E cohorts.
|
27354468 |
2017 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Alterations in <i>MEK1/2</i> occur in cancers, both in the treatment-naïve state and following targeted therapies, most notably BRAF and MEK inhibitors in <i>BRAF</i>-V600E-mutant melanoma and colorectal cancer.
|
28655712 |
2017 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
Oncogenic KRAS-associated gene signature defines co-targeting of CDK4/6 and MEK as a viable therapeutic strategy in colorectal cancer.
|
28459468 |
2017 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
Using a recently described tumor-selective nanoparticle containing a β-catenin-targeting RNAi trigger, in combination with the FDA-approved MEK inhibitor (MEKi) trametinib, we demonstrate synergistic tumor growth inhibition in <i>in vivo</i> models of colorectal cancer, melanoma, and hepatocellular carcinoma.
|
29282298 |
2018 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Thus, targeting adaptive feedback pathways in <i>BRAF</i><sup>V600E</sup> colorectal cancer can improve efficacy, but MAPK reactivation remains an important primary and acquired resistance mechanism.<b>Significance:</b> This trial demonstrates that combined BRAF + EGFR + MEK inhibition is tolerable, with promising activity in patients with <i>BRAF</i><sup>V600E</sup> colorectal cancer.
|
29431699 |
2018 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
<i>BRAF</i><sup>V600E</sup> mutations occur in ∼10% of colorectal cancer cases, are associated with poor survival, and have limited responses to BRAF/MEK inhibition with or without EGFR inhibition.
|
29483217 |
2018 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
The combination of autophagy inhibition, anti-EGFR antibodies and checkpoint inhibitors as well as autophagy targeting, MEK inhibition and anti-EGFR antibodies or checkpoint inhibitors appears to be the best treatment approach for microsatellite instability high and stable colorectal cancer cell lines, respectively.
|
30427914 |
2018 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Efficacy of the MEK Inhibitor Cobimetinib and its Potential Application to Colorectal Cancer Cells.
|
29794421 |
2018 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
Pfizer announced plans to acquire Array BioPharma, maker of a BRAF-MEK inhibitor combination that is currently approved for melanoma and could become a first-in-class treatment for colorectal cancer.
|
31227516 |
2019 |
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
Excitingly, we have identified novel therapeutic opportunities to overcome intrinsic and acquired resistance to MEK inhibition in colorectal cancer.
|
30353166 |
2019 |