B. J. Abbott

Human Tumour Xenograft Models for Use with an In Vitro-Based, Disease-Oriented Antitumour Drug Screening Program

Both short-term and long-term xenograft models may be useful in conjunction with an in vitro based disease-oriented drug screening program. Shortterm models may be most valuable in making initial assessments of the potential in vitro drug screening leads for in vivo use. We have previously shown that a substantial number of such leads may be subject to metabolic inactivation (1) and that this may be associated with a lack of therapeutic activity and a relative lack of toxicity in vivo. Certainly, rapid excretion or other pharmacologic factors may also render compounds inactive in vivo. Short-term as says may be very useful for identifying such compounds and thus setting priorities for further testing of in vitro drug leads in more rigorous longer-term models. Rational application of these longer-term models with particular attention to modeling of in situ vascular barriers, tumor microenvironment, and the natural history of the target diseases may facilitate identification and development of new drugs with significant clinical activity against the common adult solid tumors.