The present and the future landscape of treatment of advanced hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a highly lethal disease that is resistant to conventional cytotoxic drugs. Historically, effective systemic treatment options have not been available for patients with unresectable advanced disease. However, an improved understanding of the molecular mechanisms that regulate tumor initiation and progression over the past few years has led to the development of novel molecularly-targeted therapies that specifically block the different cellular signaling pathways involved. Recently, the antiangiogenesis and Raf kinase inhibitor, sorafenib showed a survival advantage in advanced stage HCC in two randomized, double-blind, controlled trials. These positive results were the first to demonstrate the efficacy of molecularly-targeted therapies in advanced HCC. Moreover, results from phase I and II trials evaluating other agents in this disease are promising and are under active clinical development. In the near future, we expect to have more data, knowledge, and evidence regarding the use of molecularly-targeted therapies in advanced HCC, both as single agents and in combination regimens. In this review, we will summarize the data concerning the present standard treatment for advanced HCC and discuss the newest, most promising clinical research that may affect the future treatment of this disease.
Rimassa
Lorenza
L
Department of Medical Oncology and Hematology, Istituto Clinico Humanitas, Via Manzoni 56, 20089 Rozzano, Milan, Italy.
Santoro
Armando
A
D001557:Benzenesulfonates / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D015195:Drug Design; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D000077157:Sorafenib; D016019:Survival Analysis
D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib