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.