title: RAS and BRAF in metastatic colorectal cancer management.
abstract: The treatment of metastatic colorectal cancer (mCRC) has been further refined with the development of monoclonal antibodies, cetuximab and panitumumab, towards the epidermal growth factor receptor (EGFR). Anti-EGFR therapy has afforded improved survival in those with wild-type RAS mCRC but provides no benefit and even harm in those with RAS-mutant tumors.BRAFmutations have also been shown to predict lack of clinically meaningful benefit to anti-EGFR therapy in mCRC. Mechanisms of resistance to EGFR blockade in wild-typeRASorBRAFmetastatic colorectal tumors appear to converge on the mitogen-activated protein kinase (MAPK) signaling pathway. Clinical trials involving combined BRAF, EGFR, and/or MAPK kinase (MEK) inhibition have shown promising activity inBRAF-mutant mCRC. Here, we review pivotal clinical trials that have redefined our treatment approach in mCRC with respect to anti-EGFR therapy based onRASandBRAFmutation status. Future studies will likely focus on improving efficacy of anti-EGFR-based therapy in mCRC through sustained MAPK pathway inhibition.
authors.affiliation: Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: May
authors.initials: M
authors.lastname: Cho
authors.affiliation: Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
authors.forename: Marwan
authors.initials: M
authors.lastname: Fakih
keywords: BRAF; RAS; cetuximab; colorectal cancer (CRC); panitumumab