title: Development of molecularly targeted therapies in hepatocellular carcinoma: where do we go now?
abstract: Hepatocellular carcinoma (HCC), once considered an orphan disease in the West, has become a global health concern. It is the third leading cause of cancer death worldwide, and its incidence continues to increase. Historically, the development of new systemic agents for advanced HCC has been lacking despite no clear benefit with traditional cytotoxic therapies. Although two randomized studies with sorafenib for the treatment of HCC patients have recently been completed, survival benefits have been modest and highlight the unmet medical need among patients with HCC. Given the clear need, clinical development of novel systemic agents in HCC has begun in earnest. These clinical studies are founded on a growing body of basic and translational science that has identified several potential molecular targets in HCC. The successful development of such targeted agents in the future will be linked to our ability to appropriately select patients for treatment based on their clinical stage (including extent of liver disease and extent of tumor) and on potential predictive markers of response. Here, we review these data in the context of rational drug development in HCC in the front-line setting and in previously treated patients.
authors.affiliation: Division of Hematology/Oncology, Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, California, USA. rfinn@mednet.ucla.edu
authors.forename: Richard S
authors.initials: RS
authors.lastname: Finn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002626:Chemistry, Pharmaceutical / Q000639:trends; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib