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Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Mar 21, 2008; 14(11): 1670-1681
Published online Mar 21, 2008. doi: 10.3748/wjg.14.1670
Harnessing the RNA interference pathway to advance treatment and prevention of hepatocellular carcinoma
Patrick Arbuthnot, Liam Jed Thompson
Patrick Arbuthnot, Liam Jed Thompson, Antiviral Gene Therapy Research Unit, Department of Molecular Medicine and Haematology, University of the Witwatersrand Medical School, Private Bag 3, WITS 2050, South Africa
Author contributions: Arbuthnot PB and Thompson LJ wrote this paper, with Arbuthnot PB concentration on RNAi and Thompson LJ concentrating on HBV.
Correspondence to: Patrick Arbuthnot, Antiviral Gene Therapy Research Unit, Department of Molecular Medicine and Haema-tology, University of the Witwatersrand Medical School, Private Bag 3, WITS 2050, South Africa. patrick.arbuthnot@wits.ac.za
Telephone: +27-11-7172365
Fax: +27-11-7172395
Received: December 4, 2007
Revised: January 27, 2008
Published online: March 21, 2008
Abstract

Primary liver cancer is the fifth most common malignancy in the world and is a leading cause of cancer-related mortality. Available treatment for hepatocellular carcinoma (HCC), the commonest primary liver cancer, is rarely curative and there is a need to develop therapy that is more effective. Specific and powerful gene silencing that can be achieved by activating RNA interference (RNAi) has generated enthusiasm for exploiting this pathway for HCC therapy. Many studies have been carried out with the aim of silencing HCC-related cellular oncogenes or the hepatocarcinogenic hepatitis B virus (HBV) and hepatitis C virus (HCV). Proof of principle studies have demonstrated promising results, and an early clinical trial assessing RNAi-based HBV therapy is currently in progress. Although the data augur well, there are several significant hurdles that need to be overcome before the goal of RNAi-based therapy for HCC is realized. Particularly important are the efficient and safe delivery of RNAi effectors to target malignant tissue and the limitation of unintended harmful non-specific effects.

Keywords: RNA interference, Hepatocellular carcinoma, Hepatitis B virus, Hepatitis C virus, Molecular pathogenesis, Delivery vectors