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Growth factor receptors and related signalling pathways as targets for novel treatment strategies of hepatocellular cancer

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World Journal of Gastroenterology 2008年第1期14卷 1-14页

作者： Michael Hpfner Detlef Schuppan Hans Scherübl Institute of Physiology Charité-Universittsmedizin Berlin Campus Benjamin Franklin Berlin 12200 Germany Beth Israel Deaconess Medical Center Harvard Medical School Boston MA 02215 United States Klinik für Innere Medizin Gastroenterologie und Gastrointestinale Onkologie Klinikum am Urban Vivantes Netzwerk für Gesundheit Berlin 10967 Germany

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, roTOR 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.

关键词： Growth factor receptor Hepatocellular cancer Small molecule inhibitor Monoclonal antibody innovative cancer treatment Sorafenib Bevacizumab Erlotinib

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Targeted medical therapy of biliary tract cancer:Recent advances and future perspectives

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World Journal of Gastroenterology 2008年第46期14卷 7021-7032页

作者： Michael Hpfner Detlef Schuppan Hans Scherübl Institute of Physiology Charité-Universittsmedizin BerlinCampus Benjamin Franklin Beth Israel Deaconess Medical Center and Harvard Medical School Klinik für Innere Medizin Gastroenterologieund Gastrointestinale OnkologieKlinikum am Urban Vivantes Netzwerk für Gesundheit10967 BerlinGermany

The limited efficacy of cytotoxic therapy for advanced biliary tract and gallbladder cancers emphasizes the need for novel and more effective medical treatment options. A better understanding of the specific biological features of these neoplasms led to the development of new targeted therapies, which take the abundant expression of several growth factors and cognate tyrosine kinase receptors into account. This review will briefly summarize the status and future perspectives of antiangiogenic and growth factor receptor-based pharmacological approaches for the treatment of biliary tract and gallbladder cancers. In view of multiple novel targeted approaches, the rationale for innovative therapies, such as combinations of growth factor (receptor)-targeting agents with cytotoxic drugs or with other novel anticancer drugs will be highlighted.

关键词： Growth factor receptor Biliary tract cancer Small molecule inhibitor lonoclonal antibody innovative cancer treatment Sorafenib Bevacizumab Erlotinib

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