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Free Content Editorial [Hot topic: Hepatocyte Growth Factor and cMET, New Development in Cancer Therapies (Guest Editors: T.A. Martin and W.G. Jiang)]

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Cancer metastasis is the most life threatening event in patients with solid tumours. As a result, understanding the underlying mechanisms and searching for factors that control the metastatic spread of cancer cells are critical in the area of cancer research. Furthermore, agents that interfere with the metastasis of cancer cells are of great value in cancer treatment. Of the complex nature of cancer metastasis, a few events are key to the metastatic process, namely, loss of cell adhesiveness (to each other), breakdown of the basement membrane and extracellular matrix, intravasation and extravasation, angiogenesis and lymphangiogenesis. There are few factors that are as widely involved in the regulation of metastatic spread of cancer as hepatocyte growth factor (HGF, also known as scatter factor).

Discovered in the nineteen eighties as a potent mitogen for hepatocyte and protein factor causing scatter of epithelial cells [1,2], HGF was soon found to be a power protein factor that stimulates the aggressiveness of cancer cells, from loss of cell-cell adhesion, increased invasiveness and motility of cancer cells, to being a powerful angiogenic and lymphangiogenic factor. The first article in the current issue summarises the main characteristics of the factor in cancer [3]. The broad and potential involved involvement of HGF in cancer has inspired a great deal of interest in targeting the factor and indeed its receptor, cMET. From the development of neutralising antibodies to both HGF and its receptor and the discovery of a complete antagonist and small molecule inhibitors, there are now multiple options in targeting the cytokine axis. In the current issue, the current status of cMET inhibitors, from the chemical structure to current preclinical and clinical studies, are comprehensively reviewed by Underiner et al [4], with an excellent article from Abounader’s group showing the impressive effect of one of the compounds [5]. The clinical implications for the HGF antagonist are clear evident from Matsumoto's work [6]. New methods of targeting HGF and its receptor have been development, including the HGF activation inhibitors, HAI, and a most unexpected enzyme, matriptase-2 [7,8]. Not covered in this issue are some other technologies targeting HGF and cMET which may also have potential therapeutic implications in cancer, including small inhibitory RNA, non-specific inhibitors to HGF and inhibitor to the cMET downstream signalling pathways.

As evident from this special issue and the rapid progress in this area, one cannot resist an expectation that some of the anti-HGF/cMET agents will eventually find their way into clinical practice, particularly in the treatment of advanced cancer. It is further hoped that the current issue will provide a valuable tool and reference for industry, clinical and laboratory research into this fascinating area of cancer research.

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Document Type: Research Article

Publication date: January 1, 2010

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