PROJECT SUMMARY/ABSTRACT (DEVELOPMENTAL THERAPEUTICS) Members of the Developmental Therapeutics (DT) Program use breakthrough insights made at the Rogel Cancer Center basic science programs to discover small molecule anticancer agents that can be advanced into biomarker-driven clinical trials. The Program serves as the forum for investigators with shared interest in identification and validation of new cancer-relevant targets and development of novel anti-cancer agents that perturb epigenetic modifiers, block protein-protein interactions, inhibit kinase activities or induce degradation of cancer-relevant protein targets. The DT Program comprises 31 members from 14 departments across four schools and colleges at the University of Michigan. Total annual direct research support is $14.3M, with $6.2M (43%) from the NCI, $2.9M (21%) from other NIH support and $0.8M (5%) from other peer-reviewed sources. During the last funding period, and in close collaboration with the Structure and Drug Screening as well as Pharmacokinetics Shared Resources, DT Program members authored 552 publications, of which 16.5% are intra-programmatic and 32.8% are inter-programmatic. To further these advances, DT Program research is focused on one or more of the following Specific Aims: 1) validate novel cancer targets that are amenable to pharmacologic intervention, 2) discover, optimize and evaluate promising therapeutic agents and potential biomarkers of response in clinically relevant preclinical model systems, and 3) advance DT drug candidates into clinical trials through structured collaborations with clinical investigator teams. The overarching goal of program members is to generate critical preclinical proof-of-concept data for promising new cancer therapies in a manner that will serve to guide clinical trial design and maximize translational impact.