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.
Copyright 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.