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.

Mazzoccoli, G., Miele, L., Oben, J., Grieco, A., Vinciguerra, M., Biology, Epidemiology, Clinical Aspects of Hepatocellular Carcinoma and the Role of Sorafenib, <<CURRENT DRUG TARGETS>>, 2016; 17 (7): 783-799. [doi:10.2174/1389450117666151209120831] [http://hdl.handle.net/10807/94619]

Biology, Epidemiology, Clinical Aspects of Hepatocellular Carcinoma and the Role of Sorafenib

Miele, Luca
Secondo
;
Grieco, Antonio
Penultimo
;
2016

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.
2016
Inglese
Mazzoccoli, G., Miele, L., Oben, J., Grieco, A., Vinciguerra, M., Biology, Epidemiology, Clinical Aspects of Hepatocellular Carcinoma and the Role of Sorafenib, <<CURRENT DRUG TARGETS>>, 2016; 17 (7): 783-799. [doi:10.2174/1389450117666151209120831] [http://hdl.handle.net/10807/94619]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/94619
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