Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2016; 22(35): 7999-8009
Published online Sep 21, 2016. doi: 10.3748/wjg.v22.i35.7999
Oncolytic viruses against cancer stem cells: A promising approach for gastrointestinal cancer
Fang Huang, Bin-Rong Wang, Ye-Qing Wu, Fan-Chao Wang, Jian Zhang, Yi-Gang Wang
Fang Huang, Bin-Rong Wang, Ye-Qing Wu, Fan-Chao Wang, Jian Zhang, Yi-Gang Wang, Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
Fang Huang, School of Public Health, Zhejiang University, Hangzhou 310058, Zhejiang Province, China
Author contributions: Huang F, Wang BR, Wu YQ, Wang FC, Zhang J and Wang YG performed the literature review and drafted the manuscript; Huang F and Wang YG revised the manuscript; Huang F and Wang BR contributed equally to this work; all the authors have read and approved the final version to be published.
Supported by the National Natural Science Foundation of China, No. 81272687; the Natural Science Foundation of Zhejiang Province of China, No. LZ13H160004 and No. LY16H160056; and the 521 Talent Project of Zhejiang Sci-Tech University.
Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.
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:
Correspondence to: Dr. Yi-Gang Wang, Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, No. 5, Road 2, Xiasha District, Hangzhou 310018, Zhejiang Province, China.
Telephone: +86-571-86843187 Fax: +86-571-86843185
Received: May 2, 2016
Peer-review started: May 3, 2016
First decision: June 20, 2016
Revised: July 12, 2016
Accepted: August 10, 2016
Article in press: August 10, 2016
Published online: September 21, 2016

Gastrointestinal cancer has been one of the five most commonly diagnosed and leading causes of cancer mortality over the past few decades. Great progress in traditional therapies has been made, which prolonged survival in patients with early cancer, yet tumor relapse and drug resistance still occurred, which is explained by the cancer stem cell (CSC) theory. Oncolytic virotherapy has attracted increasing interest in cancer because of its ability to infect and lyse CSCs. This paper reviews the basic knowledge, CSC markers and therapeutics of gastrointestinal cancer (liver, gastric, colon and pancreatic cancer), as well as research advances and possible molecular mechanisms of various oncolytic viruses against gastrointestinal CSCs. This paper also summarizes the existing obstacles to oncolytic virotherapy and proposes several alternative suggestions to overcome the therapeutic limitations.

Keywords: Cancer stem cells, Gastrointestinal cancer, Oncolytic virotherapy, Molecular mechanism

Core tip: Cancer stem cells (CSCs) are derived from tumor cells, which are responsible for tumor relapse and drug resistance. The high incidence, lethality, relapse and drug resistance of gastrointestinal cancer requires a novel therapeutic strategy against CSCs. Oncolytic viruses hold much promise because they kill tumor cells but are minimally toxic to normal cells. Isolation and identification of CSC markers for treatment of gastrointestinal cancer will benefit the engineering of oncolytic viruses and targeting anti-tumor effects. This paper reviews research on oncolytic viruses against gastrointestinal CSCs, and toxicity and immunological barriers to oncolytic virotherapy, and proposes alternative strategies.