Resistance to EGF receptor-targeted monoclonal antibodies in the management of advanced colorectal cancer

SUMMARY Molecular markers that predict benefit associated with treatments for advanced colon cancer are now part of routine clinical practice. Monoclonal antibodies that target the EGF receptor have been shown to lack efficacy in cancers that have KRAS gene mutations. The antibodies are now used exclusively for patients with KRAS wild-type colon cancer. Such cancers may not respond to EGF receptor-targeted therapy at all. Those that initially respond will eventually develop resistance and inevitably progress. We will review mechanisms of primary and secondary resistance to EGF receptor monoclonal antibody therapy and suggest strategies to overcome resistance.