DEVELOPMENTAL CANCER THERAPEUTICS (DCT) PROGRAM: SUMMARY The Developmental Cancer Therapeutics (DCT) Program seeks to empower members to develop and implement new therapeutics that advance cancer treatment in our catchment population. DCT member's interests center around three aims: 1) to identify novel biomarker and lipid-specific metabolic cancer vulnerabilities; 2) to interrogate cancer-specific immunologic and oncogenic targets in human tumors; and 3) to develop and test small molecules and biologics in investigator-initiated clinical trials. Research Highlights: Intra- and inter-programmatic collaborations led to the identification of age-dependent ceramide signaling pathways that reduce anti-tumor T cell responses; elucidation of ancestry-dependent cancer risks through the identification of novel collagen modifications in a unique South Carolina Sea Island population in collaboration with Community Outreach and Engagement; identification of a critical kinase signaling pathway that results in CXCR4 dependent T-cell infiltration in T-ALL; and initiation of national trials to examine the efficacy of novel immunotherapy combinations. New compounds and biomarkers led to statewide opportunities for therapeutic intervention and prevention of human cancers impacting the HCC catchment area, including in the socioeconomically and geographically underserved Black/African American communities. Membership: DCT consists of 48 members from 12 departments, with 14 women and six members who identify as an underrepresented minority. DCT is co-led by two exceptional scientists: John O’Bryan, PhD, a basic scientist with expertise in therapeutic targeting of RAS, and Nancy Klauber-DeMore, MD, a physician-scientist surgical oncologist with expertise in translating fundamental discoveries into investigator-initiated clinical trials. Direct peer-reviewed funding is $7M, with 27 active NCI-funded projects totaling $5.1M, a 46% increase from the last funding cycle, and a growing number of multi-institutional and programmatic awards. In collaboration with Cancer Research Training and Education Coordination, multi-disciplinary collaborative research opportunities in DCT have enhanced the entire education and career development continuum, from undergraduates in minority colleges to graduate students, postdoctoral fellows, and junior clinical members leading to members mentoring 105 students and post-docs. DCT efforts culminated in 499 publications since 2018, the majority of which are collaborative (intra- and inter-programmatic and multi-institutional), with 103 published in top-tier journals (IF >10). Program Activities: DCT provides a structure to foster multidisciplinary research across programs and institutions. This process is mediated through one-on-one discussions with members, bi-weekly program meetings, annual retreats, and seminars. With investments in cutting-edge technologies, targeted faculty recruitment, inter-programmatic team-based funding initiatives ...