Abstract:
Purpose of review B-type proto-oncogene (BRAF) mutations have been observed in about 10.8% of patients with colorectal cancer (CRC). These patients do not respond to standard therapy with anti-epidermal growth factor receptor kinase (EGFR). Here we review novel BRAF inhibitors that are currently being investigated in these tumors. Recent findings Clinical experience with the BRAF inhibitor vemurafenib in CRC suggests significant differences in response compared with melanoma. Based on preclinical data, resistance to BRAF inhibitors employs alternative signaling pathways that in turn induce cell proliferation and survival. Therapeutic strategies that combine BRAF inhibitors in addition to targeted therapy with anti-EGFR monoclonal antibodies and phosphoinositide 3-kinase pathway inhibitors or standard therapy have yielded promising results in preclinical models and some reported cases. Summary Results from current clinical trials that are exploring novel BRAF inhibitors and others that employ combined therapy are eagerly awaited for the treatment of BRAF-mutated CRC. Video abstract http://links.lww.com/COON/A13. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
