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Next generation patient-derived, genetically-defined kidney and bladder cancer xenograft models for anti-cancer drug development

Yuzhuo Wang

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Canadian Institutes of Health Research (CIHR)
Over 13 thousand people are diagnosed with kidney (5,900) and bladder (7,900) cancers each year and more than 36 hundred patients die of these cancers annually (1,750 and 1,900 respectively) in Canada. New effective drugs to treat late-staged kidney and bladder cancers are highly demanded in clinic. One essential component in anti-cancer drug development is the drug evaluation models. Currently, such drug evaluation task is commonly carried out with preclinical cancer research models that consist of special, immune-deficient mice carrying grafts of cultured, commercially available human cancer cells. While such commercial cancer cell line models have merits for basic cancer research, the cell lines used in research have evolved biologically during generations of cultures and do not properly represent patients' cancers and consequently do not adequately predict efficacy of anticancer drugs in the clinic. Even when new anticancer drug candidates have successfully passed all stages of efficacy testing performed with commercial cancer cell line models, only about 5% gets approval for clinical usage by the US Food and Drug Administration. The high number of ineffective new drug candidates entering clinical trials indicates an urgent need for better ways of predicting clinical drug efficacy before drugs are tested in humans. Drs. Wang, Collins and So at the BC Cancer Agency and the Vancouver Prostate Centre propose, in collaboration with BRI Biopharmaceutical Research Inc. (www.bripharm.com), to establish next-generation patient-derived kidney and bladder cancer models, which more closely resemble patients' cancers than any existing bladder and kidney cancer models. Such developed next generation models will provide valuable tools for studying the molecular and cellular development and progression of kidney and bladder cancers, and for the development of new therapies and their application in personalized prostate cancer therapy.

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