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World J Gastroenterol. Oct 7, 2014; 20(37): 13343-13368
Published online Oct 7, 2014. doi: 10.3748/wjg.v20.i37.13343
Gene therapy in pancreatic cancer
Si-Xue Liu, Zhong-Sheng Xia, Ying-Qiang Zhong
Si-Xue Liu, Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
Zhong-Sheng Xia, Ying-Qiang Zhong, Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
Author contributions: Liu SX performed the research; Liu SX and Xia ZS analyzed the data; Liu SX and Zhong YQ wrote the review.
Correspondence to: Ying-Qiang Zhong, MD, PhD, Professor, Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Yanjiang West Road 107, Guangdong Province, China. zhongyingqiang@21cn.com
Telephone: +86-20-81332598 Fax: +86-20-81332244
Received: October 28, 2013
Revised: December 29, 2013
Accepted: June 12, 2014
Published online: October 7, 2014
Processing time: 344 Days and 16 Hours
Abstract

Pancreatic cancer (PC) is a highly lethal disease and notoriously difficult to treat. Only a small proportion of PC patients are eligible for surgical resection, whilst conventional chemoradiotherapy only has a modest effect with substantial toxicity. Gene therapy has become a new widely investigated therapeutic approach for PC. This article reviews the basic rationale, gene delivery methods, therapeutic targets and developments of laboratory research and clinical trials in gene therapy of PC by searching the literature published in English using the PubMed database and analyzing clinical trials registered on the Gene Therapy Clinical Trials Worldwide website (http://www. wiley.co.uk/genmed/ clinical). Viral vectors are main gene delivery tools in gene therapy of cancer, and especially, oncolytic virus shows brighter prospect due to its tumor-targeting property. Efficient therapeutic targets for gene therapy include tumor suppressor gene p53, mutant oncogene K-ras, anti-angiogenesis gene VEGFR, suicide gene HSK-TK, cytosine deaminase and cytochrome p450, multiple cytokine genes and so on. Combining different targets or combination strategies with traditional chemoradiotherapy may be a more effective approach to improve the efficacy of cancer gene therapy. Cancer gene therapy is not yet applied in clinical practice, but basic and clinical studies have demonstrated its safety and clinical benefits. Gene therapy will be a new and promising field for the treatment of PC.

Keywords: Pancreatic cancer; Gene therapy; Tumor suppressor; Suicide; Anti-angiogenesis; Immunotherapy; Oncogene; Multidrug resistance; Clinical trial

Core tip: This paper tries to present a full picture of gene therapy in pancreatic cancer, providing an unambiguous classification and comprehensive analysis, especially in therapeutic targets and clinical trials worldwide. From our work, you may find the hotspots in related research and the reason why they get there.