Mechanisms of resistance to anti-EGFR therapy in colorectal cancer

// Ben Zhao 1 , Lu Wang 1 , Hong Qiu 1 , Mingsheng Zhang 1 , Li Sun 1 , Ping Peng 1 , Qianqian Yu 1 and Xianglin Yuan 1 1 Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China Correspondence to: Xianglin Yuan, email: // Keywords : colorectal cancer, epidermal growth factor receptor, targeted drug, primary resistance, acquired resistance Received : May 31, 2016 Accepted : December 05, 2016 Published : December 18, 2016 Abstract Targeting the epidermal growth factor receptor (EGFR) either alone or in combination with chemotherapy is effective for patients with RAS wild type metastatic colorectal cancer (mCRC). However, only a small percentage of mCRC patients are sensitive to anti-EGFR therapy and even the best cases finally become refractory to this therapy. It has become apparent that the RAS mutations correlate with resistance to anti-EGFR therapy. However, these resistance mechanisms only account for nearly 35% to 50% of nonresponsive patients, suggesting that there might be additional mechanisms. In fact, several novel pathways leading to escape from anti-EGFR therapy have been reported in recent years. In this review, we provide an overview of known and novel mechanisms that contribute to both primary and acquired anti-EGFR therapy resistance, and enlist possible treatment strategies to overcome or reverse this resistance.