|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
These results highlight tumor microenvironment regulation of targeted inhibitor resistance in WT/WT melanoma and provide a rationale for combining MEK inhibitors with anti-ErbB3/ErbB2 antibodies in patients with WT/WT cutaneous melanoma, for whom there are no effective targeted therapy options.<b>Significance:</b> This work suggests a mechanism by which NRG1 regulates the sensitivity of WT NRAS/BRAF melanomas to MEK inhibitors and provides a rationale for combining MEK inhibitors with anti-ErbB2/ErbB3 antibodies in these tumors.<i>Cancer Res; 78(19); 5680-93.©2018 AACR</i>.
|
30115691 |
2018 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
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
|
0.100 |
Biomarker
|
group |
BEFREE |
Consistently, inhibition of SHP2 (also known as PTPN11), which links receptor tyrosine kinase signaling to the RAS-RAF-MEK-ERK pathway<sup>11,12</sup>, was shown to be ineffective in KRAS-mutant or BRAF-mutant cancer cell lines<sup>13</sup>.
|
29808006 |
2018 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
This has driven the development of a variety of pharmaceutical agents to inhibit RAF-MEK1/2-ERK1/2 signalling in cancer and both RAF and MEK inhibitors are now approved and used in the clinic.
|
29454854 |
2018 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Fedele and colleagues demonstrate that SHP2 inhibitors prevent adaptive MEK inhibitor resistance; therefore, combining MEK and SHP2 inhibitors represents an exciting new therapeutic approach for the treatment of RAS-driven cancers.<i>Cancer Discov; 8(10); 1210-2.
|
30279193 |
2018 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
A ranked list revealed MAP2K7, an essential mediator of the c-Jun N-terminal kinase (JNK) pathway, as a candidate tumor suppressor in gastric cancer, despite its mutational frequency falling within the mutational noise for this cancer type.
|
29666306 |
2018 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Inhibition of Stearoyl-CoA desaturase 1 reverts BRAF and MEK inhibition-induced selection of cancer stem cells in BRAF-mutated melanoma.
|
30558661 |
2018 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Although aberrant pathway activation occurs mostly upstream of the kinase MEK, mutations in MEK are prevalent in some cancer subsets.
|
30377225 |
2018 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
MEK inhibition is of interest in cancer drug development, but clinical activity in metastatic colorectal cancer (mCRC) has been limited.
|
30042150 |
2018 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
The RAS-RAF-MEK-ERK signaling cascade is among the most frequently mutated pathways in human cancer.
|
29540830 |
2018 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Targeting MEK protein in cancer cells usually leads to acquired resistance to MEK inhibitors and activation of the prosurvival protein Akt.
|
30647839 |
2018 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Comparative analyses demonstrate that DREBIC predicts drug response in cancer cells from a wide range of tissues with high accuracy and identifies therapeutic vulnerabilities of cancer-causing mutations to MEK inhibitors in various cancer types.
|
30323222 |
2018 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Here, we tested the frequency of activation of both kinases in HGSOC and the therapeutic potential of dual kinase inhibition.<b>Experimental Design:</b> MEK and Src activation was assayed in primary HGSOC from The Cancer Genome Atlas (TGGA).
|
29959144 |
2018 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
These studies highlight a potential to enhance the clinical benefit of BET and MEK inhibitors and provide a strong rationale for clinical evaluation of BET/MEK combination therapies in cancer.
|
29674704 |
2018 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
However, CDK4/6 inhibitor-resistant models were sensitized to MEK inhibitors, revealing reliance on active MAPK signaling to promote tumor cell growth and invasion.<b>Conclusions:</b> In sum, these studies identify MAPK reliance in acquired CDK4/6 inhibitor resistance that promotes aggressive disease, while nominating MEK inhibition as putative novel therapeutic strategy to treat or prevent CDK4/6 inhibitor resistance in cancer.<i></i>.
|
29739788 |
2018 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Combined MEKi/STAT3i overcomes these resistances and provides a novel therapeutic strategy to target the RAS and STAT3 pathway in PDAC.<b>Significance:</b> This report describes an inverse correlation between MEK and STAT3 signaling as key mechanisms of resistance in PDAC and shows that combined inhibition of MEK and STAT3 overcomes this resistance and provides an improved therapeutic strategy to target the RAS pathway in PDAC.<b>Graphical Abstract:</b> http://cancerres.aacrjournals.org/content/canres/78/21/6235/F1.large.jpg <i>Cancer Res; 78(21); 6235-46.©2018 AACR</i>.
|
30154150 |
2018 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Cell-based assays revealed that ibrutinib treatment inhibited cell growth and decreased phosphorylation of ERBB4 and downstream targets MEK and ERK in cancer cell lines with high levels of endogenous ERBB4.
|
29398709 |
2018 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Ras-MEK Signaling Mediates a Critical Chk1-Dependent DNA Damage Response in Cancer Cells.
|
28138032 |
2017 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
These studies demonstrate that serial genetic changes at the Kras/KRAS locus are frequent in cancer and modulate competitive fitness and MEK dependency.
|
28215705 |
2017 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The dual targeting of MEK and cancer metabolism may provide a useful strategy to treat this subset of lung cancer.
|
28938614 |
2017 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
The therapeutic activity depended on induction of mitochondrial cell death pathways initiated by NOXA-mediated MCL1 degradation.<b>Conclusions:</b> Our preclinical findings provide a rationale for the clinical testing of combination HDAC and MEK pathway inhibition for TNBC and IBC that exhibit elevated baseline tumor MCL1 expression.<i>Clin Cancer Res; 23(16); 4780-92.©2017 AACR</i>.
|
28465444 |
2017 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Metformin alone or in combination with MEK and glycolytic inhibitors may be a potential therapy for LGSOC, a cancer that is indolent but chemo-resistant.
|
28545687 |
2017 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
KRAS is the dominant oncogene in this cancer type and molecular rationale would indicate, that inhibitors of the downstream target MEK could be appropriate targeted agents, but clinical trials have failed so far to achieve statistically significant benefit in unselected patients.
|
28957417 |
2017 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Bilateral blockade of MEK- and PI3K-mediated pathways downstream of mutant KRAS as a treatment approach for peritoneal mucinous malignancies.
|
28640835 |
2017 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
PTEN status is a crucial determinant of the functional outcome of combined MEK and mTOR inhibition in cancer.
|
28220839 |
2017 |