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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2016; 22(30): 6876-6889
Published online Aug 14, 2016. doi: 10.3748/wjg.v22.i30.6876
Mechanisms of drug resistance in colon cancer and its therapeutic strategies
Tao Hu, Zhen Li, Chun-Ying Gao, Chi Hin Cho
Tao Hu, Chi Hin Cho, School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong, China
Zhen Li, Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, United States
Chun-Ying Gao, Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195, United States
Chi Hin Cho, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan Province, China
Author contributions: Hu T and Li Z wrote the paper; Gao CY and Cho CH contributed critical revision of the manuscript.
Conflict-of-interest statement: None.
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: Tao Hu, PhD, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China. taohu1985@hotmail.com
Telephone: +852-39436886 Fax: +852-26035139
Received: March 15, 2016
Peer-review started: March 18, 2016
First decision: May 12, 2016
Revised: May 24, 2016
Accepted: June 13, 2016
Article in press: June 13, 2016
Published online: August 14, 2016
Processing time: 142 Days and 5.1 Hours
Abstract

Drug resistance develops in nearly all patients with colon cancer, leading to a decrease in the therapeutic efficacies of anticancer agents. This review provides an up-to-date summary on over-expression of ATP-binding cassette (ABC) transporters and evasion of apoptosis, two representatives of transport-based and non-transport-based mechanisms of drug resistance, as well as their therapeutic strategies. Different ABC transporters were found to be up-regulated in colon cancer, which can facilitate the efflux of anticancer drugs out of cancer cells and decrease their therapeutic effects. Inhibition of ABC transporters by suppressing their protein expressions or co-administration of modulators has been proven as an effective approach to sensitize drug-resistant cancer cells to anticancer drugs in vitro. On the other hand, evasion of apoptosis observed in drug-resistant cancers also results in drug resistance to anticancer agents, especially to apoptosis inducers. Restoration of apoptotic signals by BH3 mimetics or epidermal growth factor receptor inhibitors and inhibition of cancer cell growth by alternative cell death pathways, such as autophagy, are effective means to treat such resistant cancer types. Given that the drug resistance mechanisms are different among colon cancer patients and may change even in a single patient at different stages, personalized and specific combination therapy is proposed to be more effective and safer for the reversal of drug resistance in clinics.

Keywords: Colon cancer; Drug resistance; ATP-binding cassette transporters; Evasion of apoptosis; Autophagy

Core tip: Drug resistance in colon cancer is still an obstacle to successful chemotherapy. This review focuses on over-expression of ATP-binding cassette transporters and evasion of apoptosis, two representatives of transport-based and non-transport-based mechanisms of drug resistance, as well as their therapeutic strategies. Given that the drug resistance mechanisms are different among colon cancer patients and may change even in a single patient at different stages, personalized and specific combination therapy is proposed to be more effective and safer for the reversal of drug resistance in the clinical setting.