Testing Chemoprevention Strategies in a Genetically Engineered Mouse Model of High-Grade Serous Carcinoma
Abstract
Given the challenges associated with effecting cures for women with tubo-ovarian high-grade serous carcinoma (HGSC), anenhanced focus on preventing these tumors is warranted. Genetically engineered mouse models (GEMMs) of cancer providetractable and relatively rapid systems with which to test cancer prevention strategies. We recently developed Ovgp1-iCreERT2mice that also carry floxed Brca1, Trp53, Rb1, and Nf1 TSG alleles (hereafter called BPRN mice). Transient tamoxifen (TAM)treatment of these mice consistently results in oviductal HGSCs after several months. The long latency and time for diseaseprogression render our BPRN model ideally suited to test potential chemopreventive agents for their ability to prevent or delayHGSC development. This project aims to test the hypotheses that PARP inhibition (Aim 1) and/or treatment with lipophilicstatins (Aim 2) will delay or prevent HGSC development in our GEMMs. We have largely completed Major Task 1 for eachAim, as proposed. For Aim 1, cohorts of BPRN mice (n=21 each) have been generated for each of 5 groups (control and fourdifferent olaparib treatment regimens). For Aim 2, cohorts of BPRN (n=20 each) and ApcPten (AP) mice (n=17 each) havebeen generated for each of 3 groups (control and two different simvastatin treatment regimens). Most of the mice have beenTAM-injected to induce tumors, have begun the proposed drug treatments, and are in the monitoring phase of the work.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2020
- Accession Number
- AD1108779
Entities
People
- Kathleen R. Cho
Organizations
- Board of Regents of the University of Michigan