Molecular Therapies in Hepatocellular Carcinoma beyond Sorafenib: Lessons from Failed Phase III Trials and Novel Targets

摘要

As the third most common cause of cancer-related mortality worldwide, hepatocellular carcinoma (HCC) continues to evade our abilities to find effective treatment. Most patients present with advanced disease with evidence of extra-hepatic spread or vascular invasion. Sorafenib was approved by the Food & Drug Administration in 2007 for the treatment of advanced HCC based on the demonstrated improved overall survival (OS) benefits, and this has led to a renewed interest in the development of molecularly targeted drugs in this disease. However, although several targeted agents have demonstrated early evidence of antitumor activity in phase I/II studies, they have failed in randomized phase III trials, highlighting the challenge of new drug development in HCC. Several new classes of molecularly targeted agents are currently under investigation in advanced HCC.