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However, there are a number of tumours that did not respond at all or responded in an early stage but became resistant in a late stage to VEGF inhibition in preclinical mouse models. In addition, anti-VEGF therapy alone appears to be ineffective in most, if not all, clinical trials. Thus, additional factors/pathways may directly drive tumour angiogenesis or switch on at certain stages to regulate tumour angiogenesis and growth in anti-VEGF-resistant tumours and combined approaches for interrupting the VEGF pathway and additi onal pathways may improve anti-angiogenic therapeutic efficacy.

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