Review in DepthPathogenesis of hepatocellular carcinomaMoradpour, Darius; Blum, Hubert E.Editor(s): Blum, Hubert E. Author Information Department of Medicine II, University of Freiburg, Germany Correspondence to Prof. Darius Moradpour, Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Rue du Bugnon 44, CH-1011 Lausanne, Switzerland Tel: +41 21 314 47 23; fax: +41 21 314 47 18; e-mail: [email protected] European Journal of Gastroenterology & Hepatology: May 2005 - Volume 17 - Issue 5 - p 477-483 Buy Abstract Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. The major aetiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. However, no clear picture of how and in what sequence these factors interact at the molecular level has emerged yet. Malignant transformation of hepatocytes may occur as a consequence of various aetiologies, such as chronic viral hepatitis, alcohol, and metabolic disorders, in the context of increased cellular turnover induced by chronic liver injury, regeneration and cirrhosis. Activation of cellular oncogenes, inactivation of tumour suppressor genes, genomic instability, including DNA mismatch repair defects and impaired chromosomal segregation, overexpression of growth and angiogenic factors, and telomerase activation may contribute to the development of HCC. Overall, HCCs are genetically very heterogeneous tumours. New technologies, including gene expression profiling and proteomic analyses, should allow us to further elucidate the molecular events underlying HCC development and identify novel diagnostic markers as well as therapeutic targets. © 2005 Lippincott Williams & Wilkins, Inc.