Core D: Preclinical Models Core

PROJECT SUMMARY/ABSTRACT
The overall purpose of the Preclinical Models Core is to facilitate the accomplishment of the translational
research goals and objectives of the SPORE by providing investigators with a biobank of state-of-the-art
patient-derived and genetically engineered mouse models (GEMMs) of prostate cancer. These models include
23 patient-derived organoid (PDO) lines and 14 patient-derived xenograft (PDX) lines, as well as GEMMs of
genetic alterations studied in the SPORE projects and organoids derived from these models. In addition, the
Preclinical Models Core will provide assistance in the design and generation of transgenic and
knockout/knockin mouse strains and will serve as a centralized repository for these mouse strains and
materials of common interest, such as dissected tissues, DNA, RNA, and protein extracts from these strains.
The Preclinical Models Core will generate, characterize, and maintain clinically and molecularly annotated
PDOs and PDXs for use by SPORE investigators; generate and provide a repository of GEMMs and murine
engineered prostate organoid models; and provide histopathologic analyses and design preclinical trials. The
Preclinical Models Core will collaborate with RP-1 to use unique PDOs with mutations in homologous
recombination genes as well as mouse organoids with BRCA2 deletion for validation studies of determinants of
PARP inhibitor sensitivity; with RP-2 to provide genetically defined models for preclinical trials to evaluate
targeting of the NRG1-HER2/3-PI3K pathway and to provide GEMMs to study the prostate microenvironment;
and with RP-3 to provide PDX, PDO, and genetically engineered mouse–derived organoid models of lineage
plasticity.

Grant Number: 5P50CA092629-24
NIH Institute/Center: NIH
Principal Investigator: Yu Chen