Core D: Animal Models

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ABSTRACT – ANIMAL MODELS CORE (CORE D) The goals of the Animal Models Core (Core D) of the Mayo Clinic Ovarian SPORE are to improve understanding of ovarian cancer and enhance the development of novel therapies by providing clinically relevant models that will be highly translatable, thereby helping investigators bring these treatments into clinical practice. Accordingly, we will use models developed from our large orthotopic patient-derived xenograft (PDX) tumor bank to test novel therapies in three of four projects. These models were initiated through support from the SPORE, an R01, and other funding sources during Years 1-10, and recapitulate the histologic and molecular features of the source tumors in SCID mice. Importantly, they also recapitulate key clinical features of the source tumors: 1) spread in the peritoneal cavity and production of ascites mimic the patient counterpart; and 2) the responses of PDXs to platinum/taxane therapy closely parallel the responses of source patients. Since the last competitive renewal, we have developed 410 new models (for a cumulative total of 661), improved engraftment efficiency, developed methods to seamlessly transfer study data to Biostatistics and Bioinformatics Core (Core C), and successfully developed ex vivo 3D culture methods. We will continue collaborating with Core C and the Biospecimens and Patient Registry Core (Core B) to select appropriate models based on source patient (e.g., clinical parameters or germline genotypes) or PDX characteristics (e.g., drug sensitivity, gene expression) and expand them for use in experiments. Each experiment will include molecular sample identification controls to assure the genetic fidelity of the individual models. In addition, in Years 11-15, we will collaborate with investigators on Projects 1 and 3 to provide immunocompetent models. To ensure that all animal experimentation can be performed in a standardized, expert and efficient manner, Core D will serve as a central resource and, in collaboration with the laboratory personnel from each project, will perform all the PDX-based animal experimentation described in the projects. Specifically, Core D will: 1) Ensure the efficient planning, breeding, purchasing, and utilization of mice to minimize waste and the number of animals used, while also reducing redundancies in personnel; 2) provide expertise in animal care, treatment, and monitoring to ensure high quality data for Translational Research Projects, Developmental Research Program projects and Career Enhancement Program awardees’ work, ensuring that all SPORE members will have access to the highest level of skills available; 3) provide both PDX and immunocompetent models to investigators for the evaluation of novel therapeutic strategies; and 4) provide PDX tumors for ex vivo 3 D culture experiments. Under the direction of the Administrative Core, the Animal Models Core will continue to make established PDXs available to SPORE investigators and the ovarian cancer research community at large in order to stimulate translational research with the goal of reducing the burden of ovarian cancer.