|
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 |
|
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
Combined blockade of MEK and PI3KCA as an effective antitumor strategy in HER2 gene amplified human colorectal cancer models.
|
31164152 |
2019 |
|
Malignant neoplasm of colon and/or rectum
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Correction: Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer.
|
31147600 |
2019 |
|
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
MEK inhibitors activate Wnt signalling and induce stem cell plasticity in colorectal cancer.
|
31097693 |
2019 |
|
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
By treating a panel of 47 human colorectal cancer cell lines with a combination of MEK- and PI3K-inhibitors, we observe a synergistic inhibition of growth in almost all cell lines.
|
30905967 |
2019 |
|
Malignant neoplasm of colon and/or rectum
|
0.100 |
Biomarker
|
disease |
BEFREE |
PI3K activation plays a central role in the acquired resistance to the combination of anti-EGFR and MEK-inhibitor in KRAS mutated colorectal cancer cell lines.
|
30691487 |
2019 |
|
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 |
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 |
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 |
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 |
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 |