|
melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
New, highly selective inhibitors of BRAF and MEK1/2 have shown promise in clinical trials, including in previously intractable diseases such as melanoma.
|
22562245 |
2013 |
|
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 |
One such mutation, MEK1(P124L), was identified in a resistant metastatic focus that emerged in a melanoma patient treated with AZD6244.
|
19915144 |
2009 |
|
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 |
CLINVAR |
Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma.
|
23569304 |
2013 |
|
melanoma
|
0.700 |
CausalMutation
|
disease |
CLINVAR |
Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma.
|
23569304 |
2013 |
|
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 |
GeneticVariation
|
disease |
CLINVAR |
Phase II trial of MEK inhibitor selumetinib (AZD6244, ARRY-142886) in patients with BRAFV600E/K-mutated melanoma.
|
23444215 |
2013 |
|
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 |
CausalMutation
|
disease |
CLINVAR |
Preexisting MEK1 exon 3 mutations in V600E/KBRAF melanomas do not confer resistance to BRAF inhibitors.
|
22588879 |
2012 |
|
melanoma
|
0.700 |
GeneticVariation
|
disease |
CLINVAR |
Prospective enterprise-level molecular genotyping of a cohort of cancer patients.
|
25157968 |
2014 |
|
melanoma
|
0.700 |
CausalMutation
|
disease |
CLINVAR |
Prospective enterprise-level molecular genotyping of a cohort of cancer patients.
|
25157968 |
2014 |
|
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 |
GeneticVariation
|
disease |
BEFREE |
Screening a larger cohort of individuals with melanoma revealed the presence of recurring somatic MAP2K1 and MAP2K2 mutations, which occurred at an overall frequency of 8%.
|
22197931 |
2011 |
|
melanoma
|
0.700 |
Biomarker
|
disease |
CTD_human |
Screening a larger cohort of individuals with melanoma revealed the presence of recurring somatic MAP2K1 and MAP2K2 mutations, which occurred at an overall frequency of 8%.
|
22197931 |
2011 |
|
melanoma
|
0.700 |
CausalMutation
|
disease |
CLINVAR |
Screening a larger cohort of individuals with melanoma revealed the presence of recurring somatic MAP2K1 and MAP2K2 mutations, which occurred at an overall frequency of 8%.
|
22197931 |
2011 |
|
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 |
Biomarker
|
disease |
LHGDN |
Surprisingly, MEK1 and ERK1/2 activities were restored in integrin alphav-negative melanoma cells by suppression of p53, whereas concomitant block of MEK1 induced apoptosis.
|
15557124 |
2004 |
|
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 |
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 |
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 |
Biomarker
|
disease |
BEFREE |
The purpose of this study was to determine the response rate (RR) for the selective, allosteric MEK1/MEK2 inhibitor trametinib (GSK1120212), in patients with metastatic BRAF-mutant melanoma.
|
23248257 |
2013 |
|
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 |
GeneticVariation
|
disease |
BEFREE |
Thus, activating MEK1 exon 3 mutations identified herein and concurrent with V600E/KBRAF do not cause BRAFi resistance in melanoma.
|
22588879 |
2012 |
|
melanoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
To compare the efficacy and tolerability of the mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase (MEK) 1/2 inhibitor selumetinib versus temozolomide in chemotherapy-naive patients with unresectable stage III/IV melanoma.
|
22048237 |
2012 |