Using BRAF(V600E) as a marker of autophagy dependence in pediatric brain tumors

Autophagy inhibition is a potential therapeutic strategy in central nervous system (CNS) tumors. The BRAF(V600E) mutation is known to affect autophagy. Our studies indicate CNS tumor cells with BRAF(V600E) mutant cells (but not wild type) display high rates of induced autophagy, are sensitive to autophagy inhibition, and display synergy when chloroquine is combined with the RAF kinase inhibitor vemurafenib or standard chemotherapeutics. Our studies also indicate chloroquine can improve vemurafenib sensitivity in intrinsically resistant cells and in a patient with induced-vemurafenib resistance. These findings suggest CNS tumors with BRAF(V600E) are autophagy-dependent and that identification of BRAF(V600E) may be a marker to identify pediatric patients with the best potential response to autophagy inhibition.