DEVELOPMENTAL THERAPEUTICS RESEARCH PROGRAM PROGRAM CODE: DT PROJECT SUMMARY/ABSTRACT The highly collaborative, transdisciplinary Developmental Therapeutics (DT) Research Program is a critical translational innovation hub for Yale Cancer Center (YCC), bridging drug discovery and experimental therapeutics to translate preclinical discoveries to patients, while returning clinical advances to the bench for refinement. To achieve this mission, DT capitalizes on the science of all six YCC Research Programs. DT assembles a critical mass of laboratory and clinical investigators who command expertise from basic and translational science to science-driven clinical trial design and implementation. DT members have the proven ability to translate findings into development, evaluation, and approval of new therapies. The breadth of expertise in DT allows its members collectively to serve as a translational touchpoint for all YCC Programs. DT’s most important focus is the transition from identification of a novel therapeutic target or strategy, through development of a drug candidate, to early-phase clinical trials and correlative science. Our goal is to translate inventive YCC science in directions informed by YCC’s strategic priorities accompanied by bidirectional community interaction. We pursue three specific aims: 1) To translate basic discoveries into clinical candidates and strategies, with a particular focus on historically undruggable targets such as p53, RAS, MYC, and immunotherapy-resistant cancers; 2) To conduct rationally designed trials of novel anticancer therapies and hypothesis-driven combinations, including immunotherapy with conventional targeted or cytotoxic therapies; and 3) To rapidly validate new anticancer therapies by incorporating molecular selection. YCC promotes transdisciplinary collaboration within DT and enhances cancer focus via inter- and intra-programmatic meetings, recruitment, space, pilot funding, support for multi-investigator grant applications, mentorship, and Shared Resource improvements. YCC members are intimately involved in pivotal advances in cancer medicine, including molecular profiling, innovations in chemical biology, and immunotherapy. We leverage scientific breadth and exceptional early-phase clinical research capacity to overcome barriers to progress in cancer therapeutics. The Early Phase Clinical Trials Network UM1, Hybrid Decentralization Project, P50 Lung, Head and Neck, and Skin SPOREs and Lead Academic Participating Site grant from the NCI National Clinical Trials Network add resources and drive DT translational efforts. DT is also focused on increasing engagement with underserved communities. DT has 59 members from 16 departments across the Schools of Medicine, Public Health, Faculty of Arts and Sciences, and Engineering & Applied Sciences. Total cancer-related funding is $23.4M (direct costs). This includes $7.9M in peer-reviewed funding, of which $4.4M is from NCI, representing a 26% increase in NCI f...