Concurrent Genomic Deletions Impact the Response to PARP Inhibition in Prostate Cancer
Abstract
Genomic studies have unveiled a diverse array of actionable molecular targets, characterized by underlying genomic alterations. Notably, genetic alterations affecting genes responsible for DNA damage repair represent one of the most prevalent occurrences, particularly enriched in metastatic castration-resistant prostate cancer (CRPC). These alterations have been closely associated with specific therapeutic vulnerabilities in prostate cancer (PCa). One key example is the presence of defects in homologous recombination (HR) DNA repair, which indicates a high likelihood of sensitivity to Poly (ADP-ribose) polymerase (PARP) inhibition. BRCA1 and BRCA2 are two genes encoding proteins essential for HR DNA repair. Consequently, cancer cells lacking BRCA1/2 heavily rely on PARP-regulated DNA repair mechanisms and exhibit heightened sensitivity to PARP inhibition. The primary goal of our research is to identify patients who would benefit most from PARP inhibition, extending beyond those solely harboring BRCA1/2 mutations. Our project aims to determine the extent to which a genomic deletion (involving RNASEH2B and RB1) on chromosome 13q can predict the response to PARP inhibition in PCa. The successful completion of this project will pave the way for a clinical trial targeting PCa patients with focal genomic deletion on chromosome 13q, which is known to occur in approximately 12 percent of CRPC tumors. This approach will significantly broaden the pool of eligible patients for PARP inhibition, potentially offering new hope for improved treatment outcomes in prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2023
- Accession Number
- AD1212997
Entities
People
- Haibo Yang
- Li Jia
- Taraswi M. Ghosh
Organizations
- Brigham and Women's Hospital