Project Details
Description
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.
Status | Finished |
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Effective start/end date | 9/1/21 → 8/31/23 |
Funding
- National Cancer Institute: $213,322.00
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