Abstract 2595: Predictive value tools as an aid in chemopreventive agent development

• Published in: Cancer research (Chicago, Ill.) Ill.), 2013-04, Vol.73 (8_Supplement), p.2595-2595
• Main Authors: Dunn, Barbara K., Steele, Vernon E., Fagerstrom, Richard M., Topp, Carol F., Ransohoff, David, Cunningham, Christopher, Lubet, Ronald A., Ford, Leslie G., Kramer, Barnett S.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2013-2595

Over the past 25 years the Chemoprevention Agent Development Research Group of the Division of Cancer Prevention in the NCI has entered approximately 800 agents into a program designed to test for cancer preventive efficacy. The first 2 key steps in the testing pathway are in vitro/in vitro morphologic assays and, for agents successful in these, anti-tumor testing (tumor incidence and multiplicity reduction) in animal tumor models. Ultimately, agents that successfully decrease tumor incidence and multiplicity in animal models could progress to testing in humans. The goal of the current project is to evaluate the success of our program by determining how accurately the earlier stage assays (morphologic assays) predict efficacy in the later-stage assays (animal tumor assays). In our approach the 208 agents that were tested in both morphologic and animal tumor assays in this program were included in our analysis. Statistical modeling of the input from the 6 most commonly used morphologic assays into predicting the efficacy of agents in animal tumor models was carried out by multimodel inference. The statistical models that were generated predicted the ability of these 6 morphologic assays to predict tumor outcomes in animal models representing (1) all tumor types, (2) breast cancer only, and (3) colon cancer only. The statistical models assigned each morphologic assay a value describing how strongly it predicted outcomes in each of the 3 animal tumor assay settings. The development of these predictive models will guide our future decision-making with respect to agent selection as well as morphologic and animal tumor assay use. Our goal is to improve the efficiency of the overall process of chemoprevention agent development. Citation Format: Barbara K. Dunn, Vernon E. Steele, Richard M. Fagerstrom, Carol F. Topp, David Ransohoff, Christopher Cunningham, Ronald A. Lubet, Leslie G. Ford, Barnett S. Kramer. Predictive value tools as an aid in chemopreventive agent development. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2595. doi:10.1158/1538-7445.AM2013-2595