Targeting DNA replication stress in SPOP-mutant prostate cancer
Official title: Harnessing synthetic lethality in DNA replication stress for SPOP-mutated castration-resistant prostate cancer.
Funded at Mayo Clinic Rochester · NIH-11334071 · Data updated 2026-11-12
A Mayo Clinic-led study aims to find a new way to treat prostate cancer that has become resistant to standard therapy, by exploiting a specific genetic alteration (SPOP mutations).
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Mayo Clinic Rochester NIH-funded |
| Lab location | 1 site (Rochester, United States) |
| Project start | September 18, 2026 |
| Project end | August 31, 2031 |
| Funding year | 2026 |
| Award (this year) | $261,801 |
| NIH project number | 1P50CA298941-01A1 |
| Project ID | NIH-11334071 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates are men with prostate cancer harboring SPOP mutations who have progressed to castration-resistant disease and are eligible for future ATR-targeted therapies.
✕Less likely to help
Patients without SPOP mutations or those not relevant to ATR-targeted approaches may not benefit from this specific strategy.
What this research studies
If you or a loved one has SPOP-mutant prostate cancer that has stopped responding to typical treatments, this study could lead to new options. Researchers will look at how blocking a DNA repair pathway called ATR affects cancer cells with SPOP mutations and may test whether combining CDK2 inhibition can boost this effect. The project uses lab experiments with cancer cells to uncover how ATR inhibition causes cancer cell death and to identify molecular targets for therapy. Results could point to a future treatment approach that makes cancer cells more vulnerable while aiming to spare normal cells.
Why it matters
Potential benefit: If successful, the work could lead to new therapies that specifically target SPOP-mutant prostate cancer, offering hope for patients with this difficult-to-treat form.
How similar studies have gone: Previous research suggests targeting DNA repair pathways can be effective in certain genetically defined cancers, but this precise SPOP-ATR approach is emerging and may be novel.
Where this research is happening
-
Mayo Clinic Rochester
Rochester, United States Active
Researchers
- Principal investigator: Domingo-Domenech, Josep Maria — Mayo Clinic Rochester
- Study coordinator: Domingo-Domenech, Josep Maria
Related research
Other NIH-funded projects on the same topics.
-
Understanding how aggressive cell states emerge in castration-resistant prostate cancer
A research project aims to uncover the hidden cell states that help prostate cancer resist standard therapy and how these states arise early in tumor development.
-
Enhancer RNA CYP11A1-eRNA in castration-resistant prostate cancer
Researchers are testing a new RNA-based target, CYP11A1-eRNA, to see if blocking it can hamper the growth of castration-resistant prostate cancer in the lab and animal models.
-
Targeted Immunostimulatory Dual Drug Conjugates for Heterogeneous Metastatic Prostate Cancer
Researchers are testing a targeted therapy approach to help people with metastatic castration-resistant prostate cancer by boosting the immune system and delivering drugs directly to cancer cells.
-
Androgen Receptor Action in Prostate Cancer that Stops Responding to Therapy
This grant supports research to understand why certain prostate cancers stop responding to AR-targeted therapies and to find new ways to target them.
-
Hyperactive methylation in a hard-to-treat prostate cancer subtype
Researchers are studying a newly identified methylation-heavy group of advanced prostate cancer to understand its biology and find clues for better treatments.
-
Therapeutic Targeting of Lineage Plasticity in Advanced Prostate Cancer
A cancer research effort aimed at understanding and tackling how aggressive prostate cancers become resistant to standard AR-targeted therapies.
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.