Targeted therapy for BRAFV600E malignant astrocytoma.

ABSTRACT:

Purpose

Malignant astrocytomas (MA) are aggressive central nervous system tumors with poor prognosis. Activating mutation of BRAF (BRAF(V600E)) has been reported in a subset of these tumors, especially in children. We have investigated the incidence of BRAF(V600E) in additional pediatric patient cohorts and examined the effects of BRAF blockade in preclinical models of BRAF(V600E) and wild-type BRAF MA.

Experimental design

BRAF(V600E) mutation status was examined in two pediatric MA patient cohorts. For functional studies, BRAF(V600E) MA cell lines were used to investigate the effects of BRAF shRNA knockdown in vitro, and to investigate BRAF pharmacologic inhibition in vitro and in vivo.

Results

BRAF(V600E) mutations were identified in 11 and 10% of MAs from two disti

SUBMITTER: Nicolaides TP 

PROVIDER: S-EPMC3638050 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature