Molecular Targeted Therapy of Hepatocellular Carcinoma – Results of the First Clinical Studies

M.      W. Wiedmann; J.      Mossner

doi:10.2174/156800911796191033

Abstract

Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis and worldwide rising incidence during the last years. Although orthotopic liver transplantation, surgical resection and local destruction (alcohol or acetic acid and thermal ablation) are the only curative approaches, this can be accomplished in a minority of patients, since most of them present with advanced disease. In addition, those patients who have undergone curative treatment experience a high tumor recurrence rate. Non-resectable HCC is associated with a poor prognosis due to wide resistance to chemotherapeutic agents. It is therefore essential to search for new therapeutical approaches. After several years of preclinical research, the first clinical study data on molecular targeting therapy are now available for this tumor entity. Inhibitors of the epidermal growth factor receptor (EGFR) family, such as erlotinib and lapatinib were recently investigated. Furthermore, bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF), sunitinib, a multiple kinase inhibitor that blocks several receptor tyrosine kinases, and sorafenib (BAY 43-9006), a multiple kinase inhibitor that blocks not only receptor tyrosine kinases but also serine/threonine kinases along the RAS/RAF/MEK/ERK pathway, were studied, as well. Until now, the only agent that has to be proven to be effective in terms of survival outcome in two phase III placebo-controlled studies is sorafenib, which became the current standard for palliative treatment.

Keywords: Hepatocellular carcinoma, molecular targeted therapy, tyrosine kinase inhibitor, non-alcoholic steatohepatitis, HER2-R, HER4-R, NEU-R, ErbB-2-R, HER3-R, heparin binding EGF, Gefitinib, Fibroblast growth factor (receptor), Percutaneous ethanol ablation, Transarterial chemo-embolization