PRE-CLINICAL CORE FACILITY B The adolescent and young adult patients with SS18-SSX-driven synovial sarcoma are a specifically underserved population. Curative systemic therapies for synovial sarcoma are lacking and represent a critical gap in knowledge and unmet medical need. Pre-Clinical Core Facility B represents a collaboration between a synovial sarcoma mouse modeler and a sarcoma clinical and preclinical quantitative imaging specialist. They already have assembled robust genetic mouse models as well as patient-derived xenograft models of synovial sarcoma for the testing of therapies recommended by the Research Projects and Core A of the proposed SS18-SSX Biology in Synovial Sarcoma Research Center. They have also already generated rigorous protocols for the quantitative assessment of multi- modal imaging in these models and tested a number of therapeutic agents. Preliminary data point encouragingly toward the observation that localized induction of mouse genetic models of synovial sarcoma share response patterns that are strikingly similar to human synovial sarcomas, with partial responses common, but in a minority of each population tested with standard cytotoxic agents. The co-directors of this core have also generated an innovative paradigm for the induction, systemic treatment, and surgical local control of genetically-initiated limb synovial sarcomas in mice that subsequently develop pulmonary metastasis at a high and measurable prevalence in the months following local control. This matches the clinical care of human patients receiving neoadjuvant chemotherapy and allows the assessment of any therapeutic strategy on both primary tumor viability and the promotion of metastatic potential. This core will perform experiments to further optimize the available models for efficient and rigorous pre-clinical trials, as well as performing such trials for a list of therapeutic opportunities already advanced by preliminary data from the Research Projects and Core A. In addition to testing efficacy in cytoreduction and prevention of metastasis, the core is poised to deliver immediately translatable imaging biomarkers of response and resistance.
