Treating prostate cancer linked to DNA-repair (BRCA2) changes
Functional Characterization and Development of Therapeutic Paradigms for DNA Damage Repair (DDR)-deficient Lethal Prostate Cancer
This project tests whether combining PSMA-targeted radiation with PARP-blocking drugs can help men whose prostate cancer has DNA repair gene changes (like BRCA2) that make hormone therapy stop working.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Icahn School of Medicine at Mount Sinai NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project ID | NIH-11301862 on NIH RePORTER |
What this research studies
The team will use patient tumor data and gene-editing (CRISPR) screens to find which DNA damage repair genes cause prostate cancer to become resistant to hormone therapy. They will study how losing BRCA2 and other DDR genes raises PSMA levels on tumors and then test whether [177Lu]-PSMA-617 radiation plus PARP inhibitors better kills DDR-deficient cancer cells. Work uses data from the PROREPAIR B cohort and laboratory models to guide therapy choices that could move into clinical testing. The goal is to find new combination approaches and biomarkers that could direct future trials for men with these gene changes.
Who could benefit from this research
Good fit: Ideal candidates are men with advanced or metastatic prostate cancer whose tumors carry DNA damage repair gene alterations such as BRCA2 or ATM.
Not a fit: Patients without DDR gene alterations or those who cannot receive PSMA-targeted therapy or PARP inhibitors may not benefit from these approaches.
Why it matters
Potential benefit: If successful, this research could lead to combination treatments that improve responses and outcomes for men with DDR-deficient prostate cancer.
How similar studies have performed: PARP inhibitors and PSMA-directed radioligand therapy have each shown benefit for some men with advanced prostate cancer, but combining them for DDR-deficient tumors is a newer approach with only early clinical data so far.
Where this research is happening
New York, United States
- Icahn School of Medicine at Mount Sinai — New York, United States (Active)
Researchers
- Principal investigator: Chakraborty, Goutam — Icahn School of Medicine at Mount Sinai
- Study coordinator: Chakraborty, Goutam
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.