title: Mechanisms of resistance to anti-EGFR therapy in colorectal cancer.
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.
authors.affiliation: Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Ben
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Peng
authors.affiliation: Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Yuan
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000068818:Cetuximab / Q000494:pharmacology / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects*; D006801:Humans; D009154:Mutation; D009362:Neoplasm Metastasis; D000077544:Panitumumab; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D047428:Protein Kinase Inhibitors; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D018631:ras Proteins; D000068818:Cetuximab
keywords: acquired resistance; colorectal cancer; epidermal growth factor receptor; primary resistance; targeted drug