Harnessing the RNA interference pathway to advance treatment and prevention of hepatocellular carcinoma.
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.
Arbuthnot
Patrick
P
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
Thompson
Liam-Jed
LJ
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000517:prevention & control / Q000628:therapy* / Q000821:virology; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006509:Hepatitis B / Q000150:complications / Q000235:genetics / Q000628:therapy; D006526:Hepatitis C / Q000150:complications / Q000235:genetics / Q000628:therapy; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000517:prevention & control / Q000628:therapy* / Q000821:virology; D035683:MicroRNAs / Q000378:metabolism; D034622:RNA Interference; D012307:Risk Factors
D035683:MicroRNAs