Molecular pathogenesis of hepatocellular carcinoma

Abstract

Hepatocarcinogenesis is a multistep process evolving from chronic hepatitis and cirrhosis to dysplastic nodules and ultimately hepatocellular carcinoma. Recent advances in molecular methods have led to a growing understanding of the underlying mechanisms of hepatocarcinogenesis. Hepatocarcinogenesis is closely associated with allelic losses, chromosomal changes, gene mutations, and epigenetic alterations. Allelic losses show a stepwise increase at different stages of hepatocarcinogenesis. Chromosomal, genetic, and epigenetic abnormalities can lead to deregulation in many cell signaling pathways implicated in tumour proliferation, progression, and survival. Discoveries and insight into these complex pathways have created opportunities for targeted agents and new therapeutic approaches for this malignant disease. More recent evidence also suggests the involvement of aberrant microRNA expression and the concept of liverspecific cancer stem cells in hepatocarcinogenesis. Detailed undeㄴstanding of the molecular pathogenesis is crucial for the development of new therapeutic approaches against hepatocellular carcinoma. This talk summarises the molecular mechanisms currently implicated in the pathogenesis of hepatocellular carcinoma and their potential roles in improving the clinical management of this disease.