Genetic and Genomic Determinants of Homologous Recombination Repair Deficiency as Treatment Selection Markers for Lethal Prostate Cancer
Abstract
Purpose: to test the main hypothesis that patients with lethal prostate cancer can be categorized into three molecular groups according to homologous recombination deficiency (HRD) status defined by deleterious mutations in HRD genes: 1) germline/somatic HRD mutations; 2) somatic-only HRD mutations; and 3) no HRD mutations; and that these groups are clinically distinct with differential responses to AR-targeting therapies versus taxane chemotherapies. Scope: The scope of the study will include prospective evaluation of men with potentially lethal prostate cancer receiving systemic treatments in order to capture a diverse cohort of men receiving contemporary treatment regimens for castration resistant prostate cancer. From clinical correlative analyses we will determine differential response to AR-directed vs taxane therapies on the basis of HRD status, and from RNA-seq analysis we will determine the gene expression profiles associated with the three HRD groups. Major activities and findings: We have successfully initiated both laboratory and clinical portions of the study in spite of limitations posed by the pandemic. All regulatory documents are in place and approved by authorities. Due to the nature of the study, major findings are not expected until later years of the project. We will gradually shift our reporting from major activities to major findings in Year 3 of the project period.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2021
- Accession Number
- AD1151220
Entities
People
- Jun Luo
Organizations
- Johns Hopkins University