Epigenetic Mechanisms of Escape from BRAF Oncogene Dependency
Abstract
About eight percent of all human tumors (including 50% of melanomas) carry gain-of-function mutations in the BRAF oncogene. Mutated BRAF and subsequent hyperactivation of the MAPK signaling pathway has motivated the use of MAPK-targeted therapies for these tumors. Despite great promise, however, MAPK-targeted therapies in BRAF-mutant tumors are limited by the emergence of drug resistance. Mechanisms of resistance include genetic, non-genetic and epigenetic alterations. Epigenetic plasticity, often modulated by histone-modifying enzymes and gene regulation, can influence a tumor cell’s BRAF dependency and therefore, response to therapy. In this review, focusing primarily on class 1 BRAF-mutant cells, we will highlight recent work on the contribution of epigenetic mechanisms to inter- and intratumor cell heterogeneity in MAPK-targeted therapy response.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 01, 2019
- Source ID
- 10.3390/cancers11101480
Entities
People
- Fallahi-sichani
- Khaliq
Organizations
- Elsa U. Pardee Foundation
- National Cancer Institute
- United States Department of Defense
- V Foundation for Cancer Research