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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2015; 21(27): 8262-8270
Published online Jul 21, 2015. doi: 10.3748/wjg.v21.i27.8262
Clusterin: Review of research progress and looking ahead to direction in hepatocellular carcinoma
Peng Xiu, Xiao-Feng Dong, Xin-Ping Li, Jie Li
Peng Xiu, Xin-Ping Li, Jie Li, Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong Province, China
Xiao-Feng Dong, Department of Hepatobiliary Surgery, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Author contributions: Xiu P and Dong XF contributed equally to this work; Xiu P and Dong XF drafted the manuscript; Li XP retrieved the relevant literature; Li J designed the structure of this article and reviewed the final manuscript prior to submission.
Supported by National Nature Science Foundation of China, No. 81172331 and No. 30972890; and Shandong Provincial Medicine and Health Science Technology Development Planning, China, No. 2013WS0145.
Conflict-of-interest statement: The authors declare that they have 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: Jie Li, MD, PhD, Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766 Jingshi Road, Jinan 250014, Shandong Province, China. lijie0503@126.com
Telephone: +86-531-89268689 Fax: +86-531-89268689
Received: December 22, 2014
Peer-review started: December 23, 2014
First decision: March 10, 2015
Revised: April 1, 2015
Accepted: May 21, 2015
Article in press: May 21, 2015
Published online: July 21, 2015
Abstract

Liver cancer, a large proportion of which is hepatocellular carcinoma (HCC), is diagnosed in more than 700000 people each year worldwide. Liver cancer is particularly prevalent in Asia, Sub-Saharan Africa and the South Pacific, where hepatitis B and hepatitis C infection rates are very high. However, due to resistance to chemotherapy, patients with intermediate and advanced-stage disease cannot benefit from this treatment. Clusterin, which is overexpressed in many different cancers, is a stress-induced cytoprotective protein that confers treatment resistance. Custirsen (OGX-011) is a novel 2’-methoxyethyl modified phosphorothioate antisense oligonucleotide that targets secretory clusterin protein expression and is currently in clinical trials for patients with different cancers. In recent years, a number of different clinical trials have been performed, and two phase III clinical trials of custirsen evaluating combinations with chemotherapy in patients with metastatic castration-resistant prostate cancer and metastatic non-small cell lung cancer are currently in progress. The aims of this review are to summarize the current state of research on clusterin, predict future research directions and analyze the potential of the clinical application of custirsen in HCC.

Keywords: Hepatocellular carcinoma, Clusterin, Custirsen, Chemotherapy, Antisense oligonucleotides

Core tip: Resistance of liver cancer cells to chemotherapy continues to be a major clinical obstacle to extending the survival rate of patients with hepatocellular carcinoma (HCC). Custirsen, targeting secretory clusterin protein expression, is currently in clinical trials for patients with different cancers and considered to play a role in chemosensitization. This review is to summarize the current state of research on clusterin, to predict future research directions and to analyze the potential of the clinical application of custirsen in HCC.