ABSTRACT, In Vivo Therapeutics Core (IVTC) The In Vivo Therapeutics Core (IVTC) is a multi-faceted Shared Resource of the Indiana University Simon Comprehensive Cancer Center (IUSCCC) that was established to facilitate the discovery and testing of novel pharmacological and cellular therapies. The IVTC is divided into five hubs of research expertise: breeding of specialized mouse strains, preclinical toxicity and efficacy testing in xenograft models, patient-derived xenograft pipelines, hematopoietic stem-cell transplant studies, and noninvasive imaging (IVIS SpectrumCT). Importantly, the IVTC is structured in a way to provide the necessary infrastructure, oversight, and expertise required to successfully meet the needs of IUSCCC investigators. The IVTC aligns with the IUSCCC Strategic Plan to prioritize testing of mechanism-based therapeutics and enhance team-catalyzed research. Given the heavy reliance of IUSCCC investigators on services provided by IVTC, there is strong rationale to support this centralized Shared Resource that will facilitate the discovery of new therapies for cancers prominent in the catchment area of Indiana. In FY2023, 57% of IVTC users were IUSCCC members conducting research for peer review (scholarly papers or grant proposals); those projects accounted for >90% of the services invoiced. For the majority of IUSCCC members, utilization of mouse models is an essential component of their ongoing research activities focused on development of novel therapies for liquid and solid tumors. To support these needs, the aims of the IVTC are to: 1) maintain on-site breeding colonies of mice, and establish patient- derived xenografts essential for the exploration, testing, and refinement of novel cancer therapeutics; 2) provide specialized core services, technology, and consultation for in vivo studies; and 3) serve as an educational resource for IUSCCC investigators and trainees. Specifically, the IVTC manages the radiation facility and performs irradiation services needed for in vitro and in vivo experiments, including hematopoietic stem-cell transplantations. The IVTC coordinates all aspects of procedures and assists with experimental design, regulatory requirements, methodology, and data interpretation for each Research Program. To increase cost- effectiveness and improve study coordination, the IVTC assumed management of the IVIS SpectrumCT for noninvasive tumor imaging during the current grant period. In addition, the IVTC works with IUSCCC research teams to coordinate timely delivery of mice and samples to other core facilities in IUSCCC and the IU School of Medicine. As a centralized facility, the IVTC will continue to provide IUSCCC investigators with advanced resources for analytical and investigational studies essential for the preclinical validation of novel drug targets and biomarkers of cancer so that innovative investigator-initiated trials can be successfully developed.