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

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