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 2 of the study. In Phase 2, the 50 drugs will receive testing against a broad variety of human neoplasms in order to identify potential niche indications for one or more of. these agents which would be worthy of clinical Phase II trials and to indicate whether total cell kill is a more robust in vitro endpoint than is cell proliferation.
Ou, Shu Xiao; Han, Dehui; Severson, Richard K et al. (2002) Birth characteristics, maternal reproductive history, hormone use during pregnancy, and risk of childhood acute lymphocytic leukemia by immunophenotype (United States). Cancer Causes Control 13:15-25 |
Swensen, A R; Ross, J A; Shu, X O et al. (2001) Pet ownership and childhood acute leukemia (USA and Canada). Cancer Causes Control 12:301-3 |
Wen, W Q; Shu, X O; Steinbuch, M et al. (2000) Paternal military service and risk for childhood leukemia in offspring. Am J Epidemiol 151:231-40 |
Ross, J A; Potter, J D; Shu, X O et al. (1997) Evaluating the relationships among maternal reproductive history, birth characteristics, and infant leukemia: a report from the Children's Cancer Group. Ann Epidemiol 7:172-9 |
Franken, M; Annis, B; Ali, A N et al. (1995) 5' Coding and regulatory region sequence divergence with conserved function of the Epstein-Barr virus LMP2A homolog in herpesvirus papio. J Virol 69:8011-9 |