Sorafenib (BAY 43-9006) in hepatocellular carcinoma patients: from discovery to clinical development.
Angiogenesis and signaling through the RAS/RAF/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK cascade have been reported to play important roles in the development of hepatocellular carcinoma (HCC). Sorafenib (Nexavar), a novel bi-aryl urea BAY 43-9006, is an orally administered multikinase inhibitor with activity against RAS/RAF kinases multikinase inhibitor with activity against RAF kinases and several receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), FLT3, Ret, and c-Kit. It is involved in angiogenic pathway and cell proliferation. Sorafenib has demonstrated potent anti-tumor activity in in vitro studies, preclinical xenograft models of different tumor types and human clinical trials. This review summarizes the history of sorafenib from its discovery by the medicinal chemistry approach through to clinical development and ongoing trials on the combination between sorafenib and trans-arterial chemoembolization (TACE) in HCC patients.
Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Centre "Giovanni Paolo II" Bari, Bari, Italy. giroran@tiscalinet.it
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D000970:Antineoplastic Agents / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000188:drug therapy*; D015394:Molecular Structure; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000627:therapeutic use*; D000077157:Sorafenib
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib