Fresh Tumor Assay for Rediscovery of Closed-Ind Drugs

Cancer drug development suffers greatly from a lack of preclinical models to reveal human disease-specific activity of new agents. We will determine whether skilled and insightful application of a fresh human tumor assay based on the concept of total tumor cell kill can identify clinical situations in which "abandoned" drugs have important clinical antineoplastic activity. We will take 40 drugs with INDs issued between 1960 and 1980 and 10 reference agents and test these drugs against fresh human normal and neoplastic tissues using the DiSC assay. The study will attempt to identify potential clinical indications for 40 closed-IND drugs. Drugs will be tested in normal human cell types, hematologic neoplasms, and solid tumors to get pilot data as to normal cell versus hematologic versus solid tumor specificity and to prepare for more extensive testing in Phase II of the study. In Phase II, the 50 drugs will receive testing against a broad variety of human neoplasms. This testing is imperative in order to identify potential niche indications for agents which would be worthy of clinical Phase II trials. This testing will also indicate whether total cell kill is a more robust in vitro endpoint than is cell proliferation.