Emre Tkacik, Kunhua Li, Gonzalo Gonzalez-Del Pino, Byung Hak Ha, Javier Vinals, Eunyoung Park, Tyler S Beyett, Michael J Eck
Upon activation by RAS, RAF-family kinases initiate signaling through the MAP kinase cascade to control cell growth, proliferation, and differentiation. Among RAF isoforms (ARAF, BRAF, and CRAF), oncogenic mutations are by far most frequent in BRAF. The BRAFV600E mutation drives more than half of all malignant melanoma and is also found in many other cancers. Selective inhibitors of BRAFV600E (vemurafenib, dabrafenib, encorafenib) are used clinically for these indications, but they are not effective inhibitors in the context of oncogenic RAS, which drives dimerization and activation of RAF, nor for malignancies driven by aberrantly dimerized truncation/fusion variants of BRAF...
March 22, 2023: Journal of Biological Chemistry