DEVELOPMENTAL THERAPEUTICS PROGRAM: PROJECT SUMMARY/ABSTRACT The objectives of the Developmental Therapeutics (DT) program are to develop new insights in to the mechanisms of action of new and established anti-cancer agents, and to exploit these findings by translating them into the clinical arena in the form of innovative phase I and II trials. The scientific goals of the program are to: (1) elucidate the mechanisms of action of new and existing therapeutic agents and approaches, and to seek opportunities for beneficial therapeutic interventions based upon promising discoveries in cancer biology emanating from the DT program and other Virginia Commonwealth University Massey Cancer Center (MCC) programs; (2) develop strategies capable of overcoming drug resistance of human malignancies to single targeted agents through the design of rational drug combinations that circumvent multiple compensatory survival pathways characteristic of cancer cells; and (3) advance emerging concepts for the treatment of human cancers into early-phase clinical trials, focusing on concepts emanating from DT program member laboratories as well as those of other MCC programs. To advance these goals, research in the program has been organized into 4 interdigitating themes with the goal of maximizing fruitful intra- and interprogrammatic interactions. These research themes include: (1) structural and computational biology and drug design; (2) mechanism-of-action studies involving new and existing drugs; (3) rational combinations of targeted agents in clinical and preclinical studies; and (4) translational implementation of emerging strategies into investigator- initiated trials. The DT program has 43 members representing 13 departments and 3 schools. The DT program has a total cancer-related funding base of $6.2 million ($5 million in peer-reviewed direct costs), of which $2.4 million was from the NCI. During 2011-2015, the DT program had a total of 696 publications, of which 22% were intraprogrammatic and 24% were interprogrammatic.