PDX Modeling Core

PROJECT SUMMARY: CORE 3 – PRECLINICAL MODELING The Preclinical Modeling Core will be co-led by Dr. Joyce Liu, a medical oncologist specializing in gynecologic cancers who has experience in the development of gyn patient-derived xenograft (PDX) and patient-derived organoid (PDO) models, and Dr. Jean Zhao, who is an expert in the development of genetically engineered

mouse models (GEMMs). The core will provide support for all three projects with a focus on targeting replication stress in uterine cancers, including (1) targeting WEE1 in uterine serous carcinomas or p53-mutated uterine cancers; (2) combined ATR inhibition and PI3K inhibition in uterine cancers; and (3) induction of

replication stress to generate anti-tumor immunity in uterine cancers through the activation of the cGAS/STING pathway. The Core will generate, characterize, and maintain preclinical models in support of each of the projects, and will provide expertise in the design of modeling experiments. The goal of Aim 1 of the Preclinical

Modeling Core is to generate, maintain, and characterize additional PDX models of endometrial cancer from patient samples. Successfully implanted models will then be passaged and fully characterized; in collaboration with the Pathology Core, histologic fidelity to the primary tumor will be assessed. Additionally, models will be

assessed for genomic fidelity to the parent tumor via next generation sequencing. In Aim 2 of the Core, we will continue to generate, maintain, and characterize PDO models of endometrial cancer from patient samples. Successful organoids will also be characterized for fidelity to the parent tumor, similar to in Aim 1. Finally, Aim

3 of the Core will focus on the generation, maintenance, and characterization of a collection of endometrial cancer GEMMs, with defined genomic characteristics selected based upon their frequent presence and clinical relevance to human endometrial cancer. The collection of fully characterized PDXs, PDOs, and GEMMs

generated and maintained by this Core will be utilized to support the experimental plans for all three projects.