An N-terminal BRAF deletion accounting for acquired resistance to RAF/EGFR inhibition in colorectal cancer

Although combination therapy with RAF and EGFR inhibitors have improved the survival outcomes of patients with BRAF-mutated colorectal cancer (CRC), acquired resistance invariably develops. The mechanisms of acquired resistance to RAF inhibitors have been largely attributed to activating Ras mutations, MAP2K mutations, and amplifications in BRAF, Ras, and EGFR. In this report, we describe a patient with BRAF-mutated CRC who acquired a N-terminal BRAF deletion involving the Ras-binding domain (RBD) after treatment with RAF/EGFR inhibitor therapy. N-terminal BRAF deletions involving the RBD are a rare mechanism of acquired resistance to RAF inhibitors, particularly in CRC where there is only one prior report in the literature.