TY - JOUR
T1 - Biology, Epidemiology, Clinical Aspects of Hepatocellular Carcinoma and the Role of Sorafenib
AU - Mazzoccoli, G
AU - Miele, Luca
AU - Oben, J
AU - Grieco, Antonio
AU - Vinciguerra, Maria
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Animals
KW - Autophagy
KW - Carcinoma
KW - Clinical Trials as Topic
KW - Female
KW - Genetic Predisposition to Disease
KW - Hepatocellular
KW - Humans
KW - Liver Neoplasms
KW - Male
KW - Niacinamide
KW - Non-alcoholic Fatty Liver Disease
KW - Phenylurea Compounds
KW - Protein Kinase Inhibitors
KW - Survival Analysis
KW - Treatment Outcome
KW - Animals
KW - Autophagy
KW - Carcinoma
KW - Clinical Trials as Topic
KW - Female
KW - Genetic Predisposition to Disease
KW - Hepatocellular
KW - Humans
KW - Liver Neoplasms
KW - Male
KW - Niacinamide
KW - Non-alcoholic Fatty Liver Disease
KW - Phenylurea Compounds
KW - Protein Kinase Inhibitors
KW - Survival Analysis
KW - Treatment Outcome
UR - https://publicatt.unicatt.it/handle/10807/94619
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84964227484&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84964227484&origin=inward
U2 - 10.2174/1389450117666151209120831
DO - 10.2174/1389450117666151209120831
M3 - Article
SN - 1389-4501
VL - 17
SP - 783
EP - 799
JO - Current Drug Targets
JF - Current Drug Targets
IS - 7
ER -