Impact of KRAS Mutations on Management of Colorectal Carcinoma

The epidermal growth factor receptor (EGFR) pathway is a therapeutic target in the management of colorectal cancer (CRC). EGFR antagonists are active in this disease; however, only a subset of patients respond to such therapy. A Kirsten ras sarcoma viral oncogene (KRAS) wild-type (WT) status of the tumor is necessary, but possibly not sufficient, for a response to anti-EGFR monoclonal antibody therapy. Mechanisms of primary resistance to such therapy in patients harboring KRAS WT tumors are discussed. Strategies to overcome resistance to anti-EGFR monoclonal antibody therapy, including novel agents and combinations of novel therapies, are explored. Also, the use of anti-EGFR monoclonal antibodies in the adjuvant and neoadjuvant setting is reviewed.