Presently, the screening and testing of new drugs for efficacy against cancer cells is an expensive and time consuming process. In addition, traditional methodologies rely heavily on static in vitro assays, the use of live animal tests, extrapolation of results to humans, and clinical trials. The use of new techniques that can streamline this process have the potential to speed product development by reducing costs and increasing the amount of information derived from testing. It is the long-range goal to develop a system for the in vitro screening and testing of agents for anti-neoplastic activity and toxicity using human target and non-target cells. The specific aims of the experiments are to validate a prototype, intra-active, in vitro system as a screening method for drugs and pro-drugs with anti-neoplastic potential. Cyclophosphamide and tamoxifen, with known anti-neoplastic activity, will be used in a proprietary, multicellular, in vitro system with appropriate transformed human target cells and transformed, but relatively differentiated non-target cell types. Human, metabolically competent cells will be included within this system to examine the potential effects of Phase 1 and 11 enzymes on the activation and detection of pro-drugs and the detoxification of active compounds.Awardee's statement of the potential commercial applications of the research: Current procedures for screening natural products and new compounds for antineoplastic activity depends upon an involved and complex series of in vitro and in vivo assays. We have been involved in developing an intra-active system using different types of human cells to model human pharmacokinetics. This system holds the promise of reducing the use of animals in drug screening and the time that it presently required to adequately test new compounds.National Cancer Institute (NCI)
