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NIH Clinical Pharmacology 3-25-10Xenograft Disadvantages• Atypical biological behavior– Metastases are rare– Survival not an ideal endpoint, with historical deaths from tumorbulk, not invasion– Short doubling times– Less necrosis, better blood supply• Positive predictive value is poor• Poorly mimics the tumor microenvironment– Human tumor cells with murine stroma– Host directed therapies (immunomodulation, stromal tissuetargets) may not be applicable• Species specific differences between humans and mice– Examples: Antibody biopharmaceutics that only recognizehuman targets22
NIH Clinical Pharmacology 3-25-10Low Passage Patient TumorgraftsPrimary human tumors•Primary--R. A. Weinberg, in The Biology of Cancer, 2007(Courtesy of W. Hait)23
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