BRAF — a tumour-agnostic drug target with lineage-specific dependencies

Nature Reviews Clinical Oncology, Published online: 26 January 2024; doi:10.1038/s41571-023-00852-0Various BRAF alterations are found and function as oncogenic drivers across diverse cancer types. BRAF inhibitor-based therapy has improved outcomes for patients with cancers harbouring BRAFV600 mutations, although resistance develops in most, and the current inhibitors are not effective against other types of BRAF alterations. In this Review, the authors describe the mechanisms underlying oncogenic BRAF signalling, as well as pan-cancer and lineage-specific mechanisms of intrinsic, adaptive and acquired resistance to BRAF inhibitors. They also discuss novel RAF inhibitors and drug combinations designed to overcome these resistance mechanisms and/or expand the applicability of molecularly targeted therapy to a broader range of BRAF-mutant cancers.
Source: Nature Reviews Clinical Oncology - Category: Cancer & Oncology Authors: Source Type: research