Title:Biology, Epidemiology, Clinical Aspects of Hepatocellular Carcinoma and the Role of Sorafenib
Volume: 17
Issue: 7
Author(s): Gianluigi Mazzoccoli, Luca Miele, Jude Oben, Antonio Grieco, Manlio Vinciguerra
Affiliation:
关键词:
索拉非尼；肝细胞癌；NASH； HBV；HCV；肝硬化。
摘要: 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.
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