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Histopathologic and Mechanistic Assessment of Angiogenesis Inhibitor Related Toxicities: A Cross-Sectoral, Multi-disciplinary Approach (ANGIOTOX)
Start date: Jul 1, 2010, End date: Jun 30, 2014 PROJECT  FINISHED 

Inhibition of angiogenesis, the formation of new blood vessels from pre-existing vasculature, is a well established therapeutic strategy against cancer. Inhibitors of angiogenesis have been developed to block tumour growth and metastasis, and a number of these inhibitors are now clinically approved. However, contrary to initial expectations, angiogenesis inhibitors can cause a range of toxicities in patients. AngioTox is a cross-sectoral collaboration in the field of biomedicine, responding to a pressing need to understand mechanisms of toxicity associated with angiogenesis inhibitor treatment. AngioTox is comprised of academic groups, SMEs, a global pharmaceutical leader in angiogenesis inhibitor development, and a large company concerned with monitoring drug modulation of cellular pathways. The goal of this consortium is to facilitate comprehensive histopathologic and mechanistic assessment of angiogenesis inhibitor related toxicities following treatment with the two main class of angiogenesis inhibitor; monoclonal antibodies and tyrosine kinase inhibitors. A combined in vivo modelling and digital histopathology approach will be engaged to comprehensively describe a new AngioTox Safety Panel of toxicologic markers. We will develop automated image analysis algorithms to enable quantification of morphological markers of angiogenesis inhibitor toxicity, and will undertake molecular profiling and ex-vivo studies to gain insight into mechanistic pathways. Specialized secondments proposed within AngioTox will facilitate several opportunities for high-end training of researchers across both industry and academia. Findings from the AngioTox programme may be directly utilised by academic, clinical and industry-based investigators to facilitate improved screening of angiogenesis inhibitor toxicologic parameters, inform clinical drug dosing regimens, facilitate the development of more specific and potent angiogenesis inhibitors, and significantly improve patient care.

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