Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF^V600E-Mutant Human Glioma.

ABSTRACT:

Purpose

Selective RAF-targeted therapy is effective in some patients with BRAF^V600E-mutated glioma, though emergent and adaptive resistance occurs through ill-defined mechanisms.

Experimental design

Paired pre-/post- RAF inhibitor (RAFi)-treated glioma samples (N = 15) were obtained and queried for treatment-emergent genomic alterations using DNA and RNA sequencing (RNA-seq). Functional validation of putative resistance mechanisms was performed using established and patient-derived BRAF^V600E-mutant glioma cell lines.

Results

Analysis of 15 tissue sample pairs identified 13 alterations conferring putative resistance were identified among nine paired samples (including mutations involving ERRFI1, BAP1, ANKHD1, and MAP2K1). We p

SUBMITTER: Schreck KC 

PROVIDER: S-EPMC8595717 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature