Preclinical efficacy of a RAF inhibitor that evades paradoxical MAPK pathway activation in protein kinase BRAF-mutant lung cancer.

ABSTRACT: Oncogenic activation of protein kinase BRAF drives tumor growth by promoting mitogen-activated protein kinase (MAPK) pathway signaling. Because oncogenic mutations in BRAF occur in ∼2-7% of lung adenocarcinoma (LA), BRAF-mutant LA is the most frequent cause of BRAF-mutant cancer mortality worldwide. Whereas most tumor types harbor predominantly the BRAF^V600E-mutant allele, the spectrum of BRAF mutations in LA includes BRAF^V600E (∼60% of cases) and non-V600E mutant alleles (∼40% of cases) such as BRAF^G469A and BRAF^G466V The presence of BRAF^V600E in LA has prompted clinical trials testing selective BRAF inhibitors such as vemurafenib in BRAF^V600E-mutant patients. Despite promising clinical efficacy, both innate and acquired re

SUBMITTER: Okimoto RA 

PROVIDER: S-EPMC5127364 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature