Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jan 7, 2008; 14(1): 1-14
Published online Jan 7, 2008. doi: 10.3748/wjg.14.1
Growth factor receptors and related signalling pathways as targets for novel treatment strategies of hepatocellular cancer
Michael Höpfner, Detlef Schuppan, Hans Scherübl
Michael Höpfner, Institute of Physiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin 12200, Germany
Hans Scherübl, Klinik für Innere Medizin, Gastroenterologie und Gastrointestinale Onkologie, Klinikum am Urban, Vivantes Netzwerk für Gesundheit, Berlin 10967, Germany
Detlef Schuppan, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
Correspondence to: Hans Scherübl, Professor, Dr, Klinik für Innere Medizin, Gastroenterologie und Gastrointestinale Onkologie, Klinikum Am Urban, Vivantes Netzwerk für Gesundheit, Dieffenbachstrasse 1, Berlin 10967, Germany. hans.scheruebl@vivantes.de
Telephone: +49-30-130225201
Fax: +49-30-130225205
Received: May 22, 2007
Revised: October 10, 2007
Published online: January 7, 2008

Growth factors and their corresponding receptors are commonly overexpressed and/or dysregulated in many cancers including hepatocellular cancer (HCC). Clinical trials indicate that growth factor receptors and their related signalling pathways play important roles in HCC cancer etiology and progression, thus providing rational targets for innovative cancer therapies. A number of strategies including monoclonal antibodies, tyrosine kinase inhibitors (“small molecule inhibitors”) and antisense oligonucleotides have already been evaluated for their potency to inhibit the activity and downstream signalling cascades of these receptors in HCC. First clinical trials have also shown that multi-kinase inhibition is an effective novel treatment strategy in HCC. In this respect sorafenib, an inhibitor of Raf-, VEGF- and PDGF-signalling, is the first multi-kinase inhibitor that has been approved by the FDA for the treatment of advanced HCC. Moreover, the serine-threonine kinase of mammalian target of rapamycin (mTOR) upon which the signalling of several growth factor receptors converge plays a central role in cancer cell proliferation. mTOR inhibition of HCC is currently also being studied in preclinical trials. As HCCs represent hypervascularized neoplasms, inhibition of tumour vessel formation via interfering with the VEGF/VEGFR system is another promising approach in HCC treatment. This review will summarize the current status of the various growth factor receptor-based treatment strategies and in view of the multitude of novel targeted approaches, the rationale for combination therapies for advanced HCC treatment will also be taken into account.

Keywords: Growth factor receptor, Hepatocellular cancer, Small molecule inhibitor, Monoclonal antibody, Innovative cancer treatment, Sorafenib, Bevacizumab, Erlotinib