Virology Group, International Centre for Genetic Engineering and Biotechnology, P.O. Box 10504, New Delhi-110067, India.
Hepatocellular carcinoma (HCC) is the fifth most common cancers in the world. Though many etiological factors are known to be associated with HCC, overwhelming lines of epidemiological evidence suggest that chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is the major risk factor. Preclinical animal models have served as a valuable tool in understanding the mechanism of HCC. While the woodchuck and duck models of hepadnaviruses have been extremely helpful in understanding the mechanism of viral replication and developing antiviral drugs against HBV, the transgenic mouse models have established the involvement of HBV in hepatocarcinogenesis. For HCV, the related flaviviruses have been used as surrogate systems for such studies. Although mice are not susceptible to HBV and HCV, their ability to replicate these viruses and to develop liver diseases characteristic of human infections provides new opportunities to study pathogenesis and develop novel therapeutics. From a number of transgenic studies, it has become evident that the X protein of HBV and the core protein of HCV have an oncogenic potential, although the signaling pathways triggered by these two viral proteins may be different. Besides, other factors such as continued cell death and regeneration associated with chronic hepatitis and accumulation of genetic aberrations, as seen in case of colorectal cancer, may have a role in multi-stage development of HCC. Examples of successful application of these models to validate known antiviral and anticancer drugs will be discussed.
