The fundamental problem in drug discovery for cancer is that the model systems are not predictive at all. ancer research at Merck Research Laboratories in West Point, Pennsylvania…Researchers blamed the failures on the fact that the drugs were being tested against mouse, not human, tumors… the xenograft tumors don't behave like naturally occurring tumors in humans – they don't spread to other tissues, for example. Thus, drugs tested in the xenografts appeared effective but worked poorly in humans.
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Science fiction is not predictive; it is descriptive.
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The in vitro cell line model was predictive for non-small cell lung cancer under the disease-oriented approach, for breast and ovarian cancers under the compound-oriented approach, and for all four tumor types together. The mouse allograft model was not predictive. The human xenograft model was not predictive for breast or colon cancers, but was predictive for non-small cell lung and ovarian cancers when panels of xenografts were used.
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In summary, mouse xenograft models should not be viewed as ideal models for cancer drug development. Altered, nonhuman host stroma, poor predictive value when applied in an empirical sense, and questionable relation to the naturally occurring human disease are but a few features, which temper enthusiasm for their use.
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It’s been well known for maybe two decades that many of these preclinical human cancer models have very little predictive power in terms of how actual human beings – actual human tumours inside patients – will respond…Preclinical models of human cancer, in large part, stink…Hundreds of millions of dollars are being wasted every year by drug companies using these [animal] models…
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The problem with animal carcinogenicity tests is not their lack of sensitivity for human carcinogens, but rather their lack of human specificity. A positive result has poor predictive value for humans.
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'Animal studies are done for legal reasons and not for scientific reasons. the predictive value of such studies is meaningless--which means our research may be meaningless.'
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