Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Dig Dis 2012;30:284–288 DOI: 10.1159/000336993 Molecular Targeted Therapy in Hepatocellular Carcinoma: Present Achievements and Future Challenges Anna Giacomin a Adriana Sergio a Veronica Vanin a Alessia Gazzola a Nora Cazzagon b Fabio Farinati a a Section of Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, Padua University, and b IRCCS-IOV, Padua, Italy hormonal therapy and immunotherapy have not demon- strated significant effects in randomized clinical trials. Recently, the discovery of new therapeutic targets in the molecular pathways involved in hepatocarcinogenesis has led to exciting results [2]. Growth Factors and Their Receptors Vascular endothelial growth factor (VEGF) plays a central role in HCC growth and invasiveness, and the hu- manized monoclonal antibody bevacizumab has been applied in advanced HCC with encouraging results. In phase II trials it showed, as a single agent, a significant reduction in tumor arterial enhancement and circulating VEGF-A, with a 6-month progression-free survival of 65% and 13% objective responses. In combination with gemcitabine or capecitabine and oxaliplatin, the response rates were 10–20% and stable disease 27–78%, respective- ly [3, 4]. Bevacizumab has a favorable safety profile and rare severe adverse events, especially in elderly patients. Vatalanib and sunitinib have also been tested to block VEGF receptor (VEFGR). The former, an oral inhibitor of VEGF, platelet-derived growth factor (PDGF) and ba- Key Words Hepatocellular carcinoma  Targeted therapy  Molecular agents Abstract Therapeutic options in advanced stage hepatocellular carci- noma have been very poor until the discovery of new thera- peutic agents that target the molecular pathways involved in hepatocarcinogenesis. In this paper we try to review the most important molecular agents in development, with a specific focus on sorafenib’s role and safety profile, especial- ly in the treatment of patients with suboptimal liver function. Copyright © 2012 S. Karger AG, Basel Introduction Hepatocellular carcinoma (HCC) represents the fifth most common neoplasm in the world and the third in terms of mortality, maintaining a dismal prognosis since intermediate and advanced stages still account for a large percentage of cases [1]. Therapeutic options in advanced stage have been quite limited so far, as chemotherapy, Prof. Fabio Farinati Department of Surgical, Oncological and Gastroenterological Sciences Section of Gastroenterology, University of Padua Via Giustiniani 2, IT–35128 Padua (Italy) Tel. +39 049 821 1305, E-Mail fabio.farinati  @  unipd.it © 2012 S. Karger AG, Basel 0257–2753/12/0303–0284$38.00/0 Accessible online at: www.karger.com/ddi