Harnessing the RNA interference pathway to advance treatment and prevention of hepatocellular carcinoma

World J Gastroenterol. 2008 Mar 21;14(11):1670-81. doi: 10.3748/wjg.14.1670.

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 effecters to target malignant tissue and the limitation of unintended harmful non-specific effects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / prevention & control
  • Carcinoma, Hepatocellular / therapy*
  • Carcinoma, Hepatocellular / virology
  • Gene Expression Regulation, Neoplastic*
  • Genetic Therapy / adverse effects
  • Genetic Therapy / methods*
  • Hepatitis B / complications
  • Hepatitis B / genetics
  • Hepatitis B / therapy
  • Hepatitis C / complications
  • Hepatitis C / genetics
  • Hepatitis C / therapy
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / prevention & control
  • Liver Neoplasms / therapy*
  • Liver Neoplasms / virology
  • MicroRNAs / metabolism
  • RNA Interference*
  • Risk Factors

Substances

  • MicroRNAs