Targeting the Subtype of Metastatic Prostate Cancer Deficient in DNA Repair Capacity
Abstract
This proposal will address the challenge of effectively treating mPC by exploiting specific tumor vulnerabilities conferred by defects in HR DNA repair. The objectives are supported by compelling data derived from the PCF/SU2C Precision Medicine project, other sequencing efforts that assessed the molecular landscape of mCRPC, and striking clinical observations. We will aggressively target the subtype of DNA Repair Deficient (HRD) mCRPC to test the hypothesis that aberrations in key genes that repair DNA strand breaks by homologous recombination (HR) are predictive of meaningful clinical responses to FDA-approved genotoxic therapeutics (e.g carboplatin) and to emerging therapeutics (PARP and WEE1 inhibitors). We will also test the hypothesis that men with mPC represent a population highly enriched for germ-line aberrations in DNA repair genes irrespective of racial background. The proposal will also develop strategies to enhance initial responses and assess mechanisms of resistance to genotoxic agents.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2019
- Accession Number
- AD1094486
Entities
People
- Colin C Pritchard
Organizations
- University of Washington