Hepatitis C Virus Mediated Metastasis in Hepatocellular Carcinoma as a Therapeutic Target for Cancer Management.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer associated deaths. Prognosis is relatively poor in cases where Hepatitis C Virus (HCV) is associated as causative agent, mainly due to increased risk of metastasis. Metastasis is the major cause of all cancer related deaths. We reviewed reports linking expression of HCV encoded proteins with changes in cellular functions. We also compared reports on HCV-induced HCC with those on non-viral and Hepatitis B Virus (HBV) induced HCC. Novel therapeutic approaches for handling metastatic HCC were also reviewed. HCV infection is associated with expression of multiple pro-metastatic factors in HCC patients. HCV encoded proteins can directly induce pro-metastasis cellular functions. HCV-induced HCC has a greater chance of recurrence than any non-viral and Hepatitis B Virus (HBV) induced HCC. Recent advances in understanding of evolutionary dynamics of tumor argue that trying to prevent spreading of cancer may ultimately prove to be a better approach than striving to cure it. Inhibiting the metastasis can thereby substantially increase the survival period in patients. Host cell protein Nm23-H1 is a known suppressor of tumor metastasis and has been shown to be modulated by proteins encoded by different viruses associated with cancers. Nm23-H1 is an important therapeutic target for virus mediated malignancies. This review is an attempt to summarize the current state of understanding of cancer cell metastasis in HCV induced tumors, and argues for approaches based on targeting host and viral factors critical for cancer metastasis as therapeutic targets.