Autophagy inhibition overcomes multiple mechanisms of resistance to BRAF inhibition in brain tumors.

ABSTRACT: Kinase inhibitors are effective cancer therapies, but tumors frequently develop resistance. Current strategies to circumvent resistance target the same or parallel pathways. We report here that targeting a completely different process, autophagy, can overcome multiple BRAF inhibitor resistance mechanisms in brain tumors. BRAF^V600Emutations occur in many pediatric brain tumors. We previously reported that these tumors are autophagy-dependent and a patient was successfully treated with the autophagy inhibitor chloroquine after failure of the BRAF^V600E inhibitor vemurafenib, suggesting autophagy inhibition overcame the kinase inhibitor resistance. We tested this hypothesis in vemurafenib-resistant brain tumors. Genetic and pharmacological autophagy inhibition over

SUBMITTER: Mulcahy Levy JM 

PROVIDER: S-EPMC5241115 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature