title: Treating advanced hepatocellular carcinoma: How to get out of first gear.
abstract: Hepatocellular carcinoma is a common malignancy with a poor prognosis. Sorafenib is the only systemic therapy known to improve the overall survival of patients with advanced disease. The clinical benefit of sorafenib is modest and the mechanistic basis for its activity is unknown. Four phase 3 clinical trials have failed to improve on sorafenib in the frontline setting and no agent has been shown to impact outcomes after sorafenib failure. Several factors have contributed to this recent stall in drug development but new approaches hold promise and currently are being investigated. This review will focus on the current pipeline of experimental therapeutics for patients with advanced hepatocellular carcinoma and shed a light on scientific limitations that hamper the advancement of new therapies for this disease, and ways around it.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, New York.
authors.forename: James J
authors.initials: JJ
authors.lastname: Harding
authors.forename: Ghassan K
authors.initials: GK
authors.lastname: Abou-Alfa
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D011379:Prognosis; D000077157:Sorafenib
chemical_list: D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: angiogenic; cabozantinib; doxorubicin; everolimus; hepatocellular carcinoma; pegylated arginine deiminase (ADI-PEG 20); sorafenib; targeted therapy; tivantinib; tremelimumab