PRECISION CANCER MODELING SHARED RESOURCE – PROJECT SUMMARY/ABSTRACT The need for institutional support for pre-clinical animal testing was noted in a prior Yale Cancer Center (YCC). This capability is a key component of translating YCC laboratory discoveries into new cancer therapies. The demand for this capability was identified in a YCC membership survey and was subsequently endorsed by the Shared Resources Oversight Committee (SROC) and the YCC Internal Advisory Board (IAB). The IAB was supportive and recommended that a facility be developed and based at Yale West Campus. A committee produced an implementation plan that was endorsed by YCC Mini-Cabinet. PCM opened as a YCC Core and shared resource in development in 2019 with support from CCSG Developmental Funds. The mission of the PCM is to enable YCC members to perform state-of-the-art pre-clinical evaluation of cancer therapies and advanced imaging studies via three aims. Aim 1. Provide expert consultation and technological services for preclinical evaluation of experimental cancer therapies. Aim 2. Generate and validate novel pre- clinical mouse models and make them available for evaluation of novel therapeutics under development at Yale and other institutions. Aim 3. Provide access to and instruction for the use of advanced small animal imaging. The PCM provides state-of-the-art in vivo preclinical pharmacology services by providing comprehensive consultation integrated with cutting-edge laboratory infrastructure capable of performing a full suite of studies for evaluation of experimental anti-cancer therapies. Apart from standard in vivo tumor models, the PCM custom- develops state-of-the-art animal models tailored to evaluate an experimental therapy based on its mechanism of action. Unique models developed by PCM include i) a disseminated metastasis model for evaluating local and abscopal effects of intra tumorally injected agents, ii) immunotherapy-resistant, engineered knock-out models, and iii) tumor models calibrated for responses to standard-of-care therapeutics. The PCM has also developed 3D ex vivo models with the potential for high throughput testing of therapeutics. The exclusive availability of innovative models, expert implementation, and rapid generation of preclinical data has fueled a great interest in utilizing the PCM models for validation of immune therapies within the Yale community. Sponsored Research Agreements have been established with pharma companies who have also expressed interest in these models that may found broader industry-academic partnerships. In 2020, in response to YSM user needs for in vivo imaging, PCM obtained two new IVIS imagers and a high-resolution MRI to form imaging clusters in the vivaria of both the YSM and Yale West campus (YWC). These instruments cover a broad range of in vivo applications including bioluminescence, fluorescence, X-ray and MR imaging of live animals. PCM provides training and oversees use at both locations.