Pathways and gene expression profiles in hepatocellular carcinoma.

ABSTRACT

Hepatocarcinogenesis is a process attributed to progressive genomic changes which alter the hepatocellular phenotype producing cellular intermediates evolving into clearly neoplastic cells (hepatocellular carcinoma, HCC). During the preneoplastic phase, the liver is often the site of chronic hepatitis and/or cirrhosis, and this process leads to the production of monoclonal populations of aberrant and dysplastic hepatocytes that develop genetic and chromosomal alterations. At the moment three main molecular pathways of liver carcinogenesis have been described and several attempts of genetic classification of HCC have been proposed. The definition of genomic and molecular changes which occur during the development of HCC should improve the classification and prognostis of liver tumors. The development of sorafenib and other new targeted developing therapies were rendered possible by the discovery and understanding of the molecular and genetic pathogenesis of hepatocellular carcinoma. Besides viruses, such as Hepatitis B virus (HBV) and Hepatitis C virus (HCV), may contribute to cancer development by several ways; however, additional factors, such as host immunity and chronic inflammation and host cellular mutations also play a role in the transformation process. The understanding of these pathways will in the future enable the clinician to focus the treatment patients with HCC and customize single or combination therapy.