RNA interference-mediated prevention and therapy for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death and is on the increase worldwide. Hepatocellular carcinoma results from chronic liver disease and cirrhosis most commonly associated with chronic hepatitis B (HBV) or hepatitis C (HCV) infection. The highest incidences of HCC are found in China and Africa, where chronic HBV infection is the major risk component. In the United States, Europe and Japan, the significant increase in HCC and HCC-related deaths within the last three decades is mainly attributed to the rise in the number of HCV-infected individuals; smaller increases of HCC are associated with HBV. Given that HCV and HBV infection account for the majority of HCCs, therapeutic and prophylactic approaches to control or eliminate virus infection may prove effective in reducing the occurrence of HCC. Although anti-viral therapies exist for both HBV and HCV infections, they are ineffective for a significant number of patients. In addition, some treatments such as interferon therapy are dose limiting owing to toxic side effects. Clearly, new approaches are needed. RNA interference (RNAi)-based approaches may meet this need and have already shown promising preclinical results in cell culture and animal models. Although this paper focuses on the potential of RNAi as a prophylactic for HCC development, the potential use of RNAi-mediated approaches for HCC therapy will also be discussed.