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 percent 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 function a lHDR-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 percent) of biomarker positive patients fail to respond. Second, to increase the number of men with PC that could benefit from therapeutics targeting HDR-Dby promoting "conditional haploinsufficiency" converting HDR-competent tumors to a BRCAness phenotype.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2023
Accession Number
AD1216093

Entities

People

  • Peter S Nelson

Organizations

  • Fred Hutchinson Cancer Center

Tags

DTIC Thesaurus Topics

  • Accuracy
  • Androgen Receptors
  • Biology
  • Biospecimens
  • Cell Physiological Processes
  • Cells
  • Data Sets
  • Genetics
  • Health Services
  • Medical Personnel
  • Neoplasms
  • Organizational Structure
  • Prostate Cancer
  • Stem Cells
  • Therapy
  • Tissues
  • Whole Genome Sequencing

Fields of Study

  • Medicine

Readers

  • Molecular Biology and Genetics
  • Prostate Cancer Biology.
  • Regression Analysis.

Technology Areas

  • Biotechnology