Key Topics:
• HRD signatures and their role in prostate cancer treatment
• The limitations of relying solely on BRCA mutations for PARP inhibitor selection
• The importance of biallelic mutations in treatment response
• Recommendations for future clinical trial designs
Dr. Mercinelli discussed her research on HRD signatures in clinically advanced prostate cancer, presented at GU ASCO 2025. In conversation with Dr. Karan Jatwani from George Washington University Hospital Center, the conversation delved into the implications of her work, which challenges traditional methods of selecting patients for PARP inhibitors based solely on BRCA1 and BRCA2 mutations.
Dr. Mercinelli highlighted the importance of identifying the broader HRD phenotype, including patients with hypermethylation of BRCA, who may still benefit from PARP inhibitors despite not having detectable mutations. With an analysis of over 20,000 prostate cancer samples, her findings reveal that 10% of the population showed HRD signature positivity, primarily linked to BRCA2 biallelic alterations.