Core D - Animal Models Core

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ABSTRACT – Core D The goals of the Animal Models Core 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 from the “bench to the bedside.” To this end, we will employ models developed from our large patient-derived xenograft (PDX) `living tumor-bank' to develop novel therapies in three of the four Projects. These PDX models, which were initiated through support from the SPORE during Years 1-5, are further referred to as Avatars, as they recapitulate the histologic and molecular features of the source patients as orthotopic models in SCID mice. Moreover, these models spread throughout the peritoneal cavity, including omentum, just like the human counterpart. In addition, they recapitulate other features of the source tumors as well: 1) When models are established from patients with ascites, the Avatars also have ascites; and 2) the responses of Avatars to platinum/taxane therapy closely parallel the responses of source patients. In collaboration with the Biospecimens and Biostatistics Cores, we will select appropriate models based on source patient (such as clinical parameters or germline genotypes) or Avatar characteristics (such as drug sensitivity, mutation or gene expression profile) and expand them for use in experiments to evaluate treatment. Each experiment will include molecular sample identification controls to assure the genetic fidelity of the individual models. In addition, we will collaborate with the fourth Project (Project 8) to provide multiple immunocompetent models through a breeding program. This will include models that have been instrumental in evaluating the role of dendritic cells in immune suppression in ovarian cancer in our current funding period (Project 2). To ensure that all animal experimentation can be performed in an expert and efficient manner—and that SPORE investigators use standardized models for their varying therapeutic strategies—the Animal Models Core will serve as a central resource, and in collaboration with the laboratory personnel from each project, will perform all the animal experimentation described in the projects. Specifically, the Animal Models Core will: 1) ensure the efficient planning, breeding, purchase and utilization of mice for SPORE related work to minimize waste and the number of animals used, while also reducing redundancies in personnel; 2) provide expertise in animal care and treatment to ensure high quality data as required for Translational Research Projects as well as Developmental Research Projects and Career Development work, ensuring that  all SPORE members will have access to the highest level of skills available; 3) provide both patient-derived xenograft and immunocompetent models to investigators for the evaluation of novel therapeutic strategies in ovarian cancer; and 4) provide monitoring and biospecimen collection services for SPORE-related experiments.