Defining and Modulating BRCAness to Improve the Precision of Prostate Cancer Therapy
Abstract
Purpose: This proposal is focused on exploiting a specific subtype of metastatic CRPC, termed Homology Directed DNA Repair Deficient (HDR-D) prostate cancer (PC) to enhance treatment outcomes, reduce morbidity and improve survival. HDR-D represents at least 20% of metastatic PC and is most commonly identified through the genomic analysis of biopsies from metastatic tumors and identifying mutations in BRCA1, BRCA2 and related genes.Scope: This proposal is designed to address two challenges: First, to improve the accuracy of detecting PCs with functional HDR-D for appropriate treatment allocation. It is clear from prospective studies that simply evaluating the mutation status of HDR-associated genes lacks precision for predicting treatment responses: a high percentage(>50%) of biomarker positive patients fail to respond. Second, to increase the number of men with PC that could benefit from therapeutics targeting HDR-D by promoting conditional haploinsufficiency converting HDR-competent tumors to a BRCAness phenotype.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2023
- Accession Number
- AD1216099
Entities
People
- Colin C Pritchard
Organizations
- University of Washington