melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
BRAF and MEK1/2 inhibitors are effective in melanoma but resistance inevitably develops.
|
31727888 |
2019 |
melanoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Combinatorial inhibition of MEK1/2 and CDK4/6 is currently undergoing clinical investigation in NRAS-mutant melanoma.
|
30819666 |
2019 |
melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
It inhibited colorectal cancer and melanoma cell proliferation much more effectively than its negative control MS432N (<b>24</b>), and its effect was phenocopied by MEK1/2 knockdown.
|
31730343 |
2019 |
melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
A MEK1/2 inhibitor, binimetinib is promising as a therapeutic agent for malignant melanoma with N-RAS mutation.
|
31129802 |
2019 |
melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
Biomarker results from a phase II study of MEK1/2 inhibitor binimetinib (MEK162) in patients with advanced <i>NRAS</i>- or <i>BRAF</i>-mutated melanoma.
|
30956763 |
2019 |
melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
Together, these pathways provide a way to activate MAPK signaling downstream of BRAF and MEK1 inhibitors, which are commonly used to treat melanoma.
|
30543563 |
2019 |
melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
ERK1 is the immediate downstream target of MEK1/2, which is druggable with trametinib, an approved therapeutic for melanoma.
|
30804427 |
2019 |
melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
Recent clinical and therapeutic success with RAF and MEK1/2 inhibitors has revolutionized the existing treatment schemes for previously incurable cancers like melanomas.
|
31662208 |
2019 |
melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
While the role of the BRAF-MEK1/2-ERK1/2 pathway in melanoma is well established, the involvement of mitogen-activated protein kinases MEK5-ERK5 remains poorly explored.
|
29483645 |
2018 |
melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
Coupling MEK1/2 inhibitors with B-Raf inhibitors is more effective in treating such melanomas and dual therapy is now the standard of care.
|
30118796 |
2018 |
melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
The mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2) inhibitor trametinib has shown promising therapeutic effects on melanoma, but its efficacy on colorectal cancer (CRC) is limited.
|
28756770 |
2017 |
melanoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
In patients with BRAF-mutated melanoma specific inhibitors of BRAF<sup>V600E</sup> and MEK1/2 frequently induce initial tumor reduction, frequently followed by relapse.
|
28720543 |
2017 |
melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
Targeting BMK1 Impairs the Drug Resistance to Combined Inhibition of BRAF and MEK1/2 in Melanoma.
|
28387310 |
2017 |
melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
phase II and III clinical trials demonstrated modest anti- tumor activity of Binimetinib (MEK162) - a potent allosteric inhibitor of MEK1 and MEK2- in patients with advanced NRAS mutant melanoma.
|
28919996 |
2017 |
melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
Corrigendum: Targeting BMK1 Impairs the Drug Resistance to Combined Inhibition of BRAF and MEK1/2 in Melanoma.
|
28548101 |
2017 |
melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
MEK1/2 and BRAF<sup>V600E</sup> inhibitors are used to treat BRAF<sup>V600E</sup>-positive melanoma, with other cancers under evaluation.
|
28986383 |
2017 |
melanoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Cobimetinib: inhibiting MEK1/2 in BRAF V600-mutant melanoma.
|
28112278 |
2016 |
melanoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Taken together, our data indicate that preexisting MEK1(P124) mutations are associated with a reduced response to BRAF inhibitor therapy and identify a subset of patients with BRAF-mutant melanoma likely to benefit from combination therapies involving MEK or ERK inhibitors.
|
25370473 |
2015 |
melanoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
This MEK1(T55delins) (RT) mutation could be traced back to a fraction of the pre-treatment lesion and not only provided protection against vemurafenib but also promoted local invasion of transplanted melanomas.
|
26105199 |
2015 |
melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
PI3'-kinase inhibition forestalls the onset of MEK1/2 inhibitor resistance in BRAF-mutated melanoma.
|
25472943 |
2015 |
melanoma
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
Single treatment of BRAF mutant melanoma cell lines with vemurafenib or dabrafenib (BRAF inhibitors) alone or in combination with trametinib (MEK1/2 inhibitor) resulted in overexpression of Mcl-1.
|
26497853 |
2015 |
melanoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
In recent years, intracellular signal transduction via RAS-RAF-MEK-ERK has been successfully targeted in new treatment approaches for melanoma using small molecule inhibitors against activated BRAF (V600E mutation) and activated MEK1/2.
|
25654738 |
2015 |
melanoma
|
0.700 |
CausalMutation
|
disease |
CLINVAR |
Novel ATP-competitive MEK inhibitor E6201 is effective against vemurafenib-resistant melanoma harboring the MEK1-C121S mutation in a preclinical model.
|
24448821 |
2014 |
melanoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Our data confirming that MEK2(C125S), but not the synonymous MEK1(C121S) protein, confers resistance to combination therapy highlight the functional differences between these kinases and the preponderance of MEK2 mutations in combination therapy-resistant melanomas.
|
25452114 |
2014 |
melanoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
We found that the acquired MEK1-C121S mutation in BRAF-V600E mutant melanoma conferred resistance to both vemurafenib and selumetinib but not E6201.
|
24448821 |
2014 |