Molecular targeted therapy of hepatocellular carcinoma - results of the first clinical studies.

Abstract

Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis and worldwide rising incidence during the last years. Although orthotopic liver transplatation, 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.

• Authors: Marcus W Wiedmann, Joachim Mössner
• Journal: Current cancer drug targets (Curr Cancer Drug Targets) Vol. 11 Issue 6 Pg. 714-33 (Jul 2011) ISSN: 1873-5576 [Electronic] Netherlands
• PMID: 21599629 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Vascular Endothelial Growth Factor A
• ErbB Receptors

Topics

• Antineoplastic Agents (therapeutic use)
• Carcinoma, Hepatocellular (drug therapy, metabolism)
• Clinical Trials, Phase III as Topic
• ErbB Receptors (antagonists & inhibitors)
• Humans
• Liver Neoplasms (drug therapy, metabolism)
• Molecular Targeted Therapy
• Protein Kinase Inhibitors (therapeutic use)
• Signal Transduction (drug effects)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors)