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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jan 15, 2016; 8(1): 1-7
Published online Jan 15, 2016. doi: 10.4251/wjgo.v8.i1.1
Clinical efficacy and drug resistance of anti-epidermal growth factor receptor therapy in colorectal cancer
Hakan Kocoglu, Fatih Mehmet Velibeyoglu, Mustafa Karaca, Deniz Tural
Hakan Kocoglu, Fatih Mehmet Velibeyoglu, Deniz Tural, Department of Medical Oncology, Bakirkoy Education and Research Hospital, 34900 Istanbul, Turkey
Mustafa Karaca, Department of Medical Oncology, Gazi University Faculty of Medicine, 06500 Ankara, Turkey
Author contributions: All authors contributed to this manuscript.
Conflict-of-interest statement: All authors declared no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Deniz Tural, MD, Department of Medical Oncology, Bakirkoy Education and Research Hospital, Zuhuratbaba District, Tevfik Saglam Street, No: 11, 34900 Istanbul, Turkey. deniztural@gmail.com
Telephone: +90-212-4147171 Fax: +90-212-4147172
Received: April 23, 2015
Peer-review started: April 24, 2015
First decision: September 2, 2015
Revised: November 12, 2015
Accepted: December 7, 2015
Article in press: December 8, 2015
Published online: January 15, 2016
Abstract

Colorectal cancer (CRC) ranked third in cancer related death and its incidence has been increasing worldwide. In recent decades important therapeutic advances have been developed in treatment of metastatic CRC (mCRC), such as monoclonal antibodies against epidermal growth factor receptor (anti-EGFR), which provided additional clinical benefits in mCRC. However, anti-EGFR therapies have limited usage due to approximately 95% of patients with KRAS mutated mCRC do not response to anti-EGFR treatment. Thus, KRAS mutation is predictive of nonresponse to anti-EGFR therapies but it alone is not a sufficient basis to decide who should not be received such therapies because; approximately fifty percent (40%-60%) of CRC patients with wild-type KRAS mutation also have poor response to anti-EGFR based treatment. This fact leads us to suspect that there must be other molecular determinants of response to anti-EGFR therapies which have not been identified yet. Current article summarizes the clinical efficacy of anti-EGFR therapies and also evaluates its resistance mechanisms.

Keywords: Colorectal cancer, Epidermal growth factor receptor, KRAS mutation, Anti-epidermal growth factor receptor antibody, Drug resistance

Core tip: Molecular targeting agents, such as monoclonal antibodies against epidermal growth factor receptor (anti-EGFR), provide additional clinical benefits in metastatic colorectal cancer (CRC). However, anti-EGFR therapies have limited usage due to approximately 95% of patients with KRAS mutated metastatic CRC do not response to anti-EGFR treatment. Thus, KRAS mutation is predictive of nonresponse to anti-EGFR therapies but it alone is not a sufficient basis to decide who should not be received such therapies because approximately fifty percent (40%-60%) of CRC patients with wild-type KRAS mutation also have poor response to anti-EGFR based treatment. This fact leads us to suspect that there must be other molecular determinants of response to anti-EGFR therapies which have not been identified yet. Current article summarizes the clinical efficacy of anti-EGFR therapies and also evaluates its resistance mechanisms.