ABSTRACT
Serine/threonine-protein kinase BRAF, a downstream effector of the RAS-MEK-ERK signaling pathway, has emerged as an important biological marker for diagnosis, prognostication, and therapeutic selection for patients with cancer. Emerging biomarkers assessing BRAF and the pathway focus on identifying actionable drivers and determinants of resistance. BRAF mutations also occur at a low frequency in other cancers, including glioma, ependymoma, non-Hodgkin's lymphoma, acute lymphoblastic leukemia, as well as non-small cell lung, hepatocellular, gastric, and esophageal carcinomas. Although single agent and combinations BRAF and MEK induce tumor response in multiple cancers and improve progression free survival and OS in melanoma, patient benefit from therapy may be short lived or even absent due to resistance mechanisms. BRAF gene mutation testing can assist with determining diagnosis, prognosis, and selection of treatment for patients with certain cancers. Multiple epigenetic resistance mechanisms have been identified from the analysis of preclinical models and patient-derived tumor samples.
