Combined BRAF^V600E and MEK blockade for BRAF^V600E-mutant gliomas.

ABSTRACT: BRAF^V600E is a common finding in glioma (about 10-60% depending on histopathologic subclassification). BRAF^V600E monotherapy shows modest preclinical efficacy against BRAF^V600E gliomas and also induces adverse secondary skin malignancies. Here, we examine the molecular mechanism of intrinsic resistance to BRAF^V600E inhibition in glioma. Furthermore, we investigate BRAF^V600E/MEK combination therapy that overcomes intrinsic resistance to BRAF^V600E inhibitor and also prevents BRAF^V600E inhibitor induced secondary malignancies. Immunoblotting and Human Phospho-Receptor Tyrosine Kinase Array assays were used to interrogate MAPK pathway activation. The cellular effect of BRAF^V600E and MEK inhibition was deter

SUBMITTER: Zhang J 

PROVIDER: S-EPMC5560871 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature