Viral Targeted Gene Therapy and Hepatocellular Carcinoma: Possible Therapeutic Prospects and Drawbacks

Abstract

Hepatocellular carcinoma (HCC) is the second leading cause of liver cancer-related death in humans; it can be a malignant or localized tumor of liver cells (hepatocytes) and development is by a multistep complex process called Hepatocarcinogenesis. Etiological agents of HCC include liver cirrhosis, chronic hepatitis due to hepatitis B virus and or hepatitis C virus infection, alcoholism, exposure to dietary carcinogenic aflatoxins and hemochromatosis. HCC may also result from production of aberrant hepatocytes and the formation of dysplastic nodules. Recent researches have revealed the involvement of aberrant microRNA (miRNA) expression and liver-specific cancer stem cells (CSCs) in HCC development. The progression of hepatocarcinogenesis is associated with multiple molecular mechanisms that involve genetic, epigenetic, and cell signaling alterations. DNA Methylation, an important epigenetic event in human carcinogenesis has been studied extensively to understand the mechanisms underlying HCC progression for optimized clinical management of HCC and the development of new therapeutic approaches to the disease. Despite current progress with the treatment of human cancers, existing therapies are limited in their abilities to cure HCC and fatality still remains high. Hence, this review critically examine the prospects of viral targeted gene therapy for effective management of HCC and the current drawbacks encountered in the use of viral vectors for immunotherapy of various human metastatic cancer stem cell forms.