title: Biology, Epidemiology, Clinical Aspects of Hepatocellular Carcinoma and the Role of Sorafenib.
abstract: Sorafenib is a small molecular inhibitor of intracellular tyrosine and serine/threonine protein kinases (VEGFR, PDGFR, CRAF and BRAF), and is thought also to induce autophagy, a chief mechanism influencing tumor growth. Sorafenib shows efficacy in the management of non-resectable hepatocellular carcinoma (HCC), which is refractory to other chemotherapeutic drugs. HCC represents a major end point of chronic liver diseases and the third leading cause of cancer-related death. In HCC patients Sorafenib increases overall survival compared to placebo. The most common chronic liver disease affecting up to 30% of the population in Western countries is non-alcoholic fatty liver disease (NAFLD), an intra-hepatic amassing of triglycerides deemed as the hepatic manifestation of insulin resistance and obesity. NAFLD encompasses a range of disorders with grades of liver damage varying from steatosis to non-alcoholic steatohepatitis (NASH), hallmarked by hepatocellular injury/inflammation in the presence or not of fibrosis. NAFLD patients progress to NASH in 10% of cases, which may progress to cirrhosis and HCC. Recent exciting studies uncovered a potential therapeutic role for Sorafenib that goes beyond HCC, and extends to cirrhotic portal hypertensive syndrome during cirrhosis, and to selective anti-fibrotic effects mediated through direct inhibition of activated hepatic stellate cells (HSC), the cellular mediators of intra-hepatic matrix deposition. The aim of this review is to concisely summarize our current knowledge of the biology, epidemiology and clinical aspects of HCC, as well as the previously under-appreciated therapeutic efficacy of Sorafenib beyond HCC. The review therefore utilizes data along the spectrum of liver diseases, including from experimental via pre-clinical to clinical.
authors.affiliation: Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit, IRCCS "Casa Sollievo della Sofferenza", Opera di Padre Pio da Pietrelcina, Cappuccini Av., San Giovanni Rotondo (FG), 71013, Italy. g.mazzoccoli@operapadrepio.it.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Mazzoccoli
authors.forename: Luca
authors.initials: L
authors.lastname: Miele
authors.forename: Jude
authors.initials: J
authors.lastname: Oben
authors.forename: Antonio
authors.initials: A
authors.lastname: Grieco
authors.forename: Manlio
authors.initials: M
authors.lastname: Vinciguerra
mesh_terms: D000818:Animals; D001343:Autophagy; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D002986:Clinical Trials as Topic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications* / Q000235:genetics; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000077157:Sorafenib; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib