Mechanisms of resistance to anti-EGFR therapy in colorectal cancer

• Published in: Oncotarget Vol. 8; no. 3; pp. 3980 - 4000
• Main Authors: Zhao, Ben, Wang, Lu, Qiu, Hong, Zhang, Mingsheng, Sun, Li, Peng, Ping, Yu, Qianqian, Yuan, Xianglin
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 17.01.2017
• Subjects: Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Cetuximab - pharmacology; Cetuximab - therapeutic use; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic - drug effects; Gene Regulatory Networks - drug effects; Humans; Mutation; Neoplasm Metastasis; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; ras Proteins - genetics; Receptor, Epidermal Growth Factor - genetics; Research Paper; Signal Transduction; primary resistance; colorectal cancer; epidermal growth factor receptor; targeted drug; acquired resistance
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.14012

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.