Blocking stromal signals to make androgen-blocking treatment work better for high-risk prostate cancer
Official title: Project 2: Overcoming Microenvironment-Mediated Resistance to AR Pathway Inhibition in High-Risk Prostate Cancer
Funded at Sloan-Kettering Inst Can Research · NIH-11173726 · Data updated 2026-11-12
Researchers are trying to improve outcomes for people with high-risk localized prostate cancer by blocking signals from nearby stromal cells so androgen-blocking drugs work more fully.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Sloan-Kettering Inst Can Research NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project start | September 14, 2001 |
| Project end | August 31, 2027 |
| Funding year | 2025 |
| Award (this year) | $212,659 |
| NIH project number | 5P50CA092629-24 |
| Project ID | NIH-11173726 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates are men with high-risk, locally advanced, or high-grade localized prostate cancer being considered for intensive neoadjuvant or early systemic androgen-receptor–targeted therapy.
✕Less likely to help
Patients with unrelated cancers, low-risk localized prostate cancer, or those with widely metastatic, heavily pretreated disease are unlikely to benefit directly from this project.
What this research studies
Researchers found with single-cell RNA sequencing of human and mouse prostates that a stromal protein called neuregulin 1 (NRG1) helps prostate cells survive when androgen signaling is shut down. Preclinical lab and mouse models show that stromal-derived NRG1 can allow cancer cells to persist after powerful androgen-receptor inhibitors. The project aims to test ways to block this microenvironment signal alongside second-generation AR pathway drugs to increase complete responses in patients with locally advanced, high-grade disease. If successful, the work could lead to clinical approaches added to current neoadjuvant or early systemic therapies to reduce recurrence.
Why it matters
Potential benefit: This approach could raise the rate of complete tumor responses and help more patients with high-risk localized prostate cancer move from disease control toward cure.
How similar studies have gone: Using second-generation androgen-receptor inhibitors earlier has improved outcomes in several trials, but targeting stromal NRG1 as a resistance mechanism is a newer strategy still largely tested in preclinical models.
Where this research is happening
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Sloan-Kettering Inst Can Research
New York, United States Active
Researchers
- Principal investigator: Carver, Brett Stewart — Sloan-Kettering Inst Can Research
- Study coordinator: Carver, Brett Stewart
Related research
Other NIH-funded projects on the same topics.
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Overcoming Resistance to AR-Targeted Therapy in High-Risk Prostate Cancer
Researchers are studying why some high-risk prostate cancers stop responding to AR pathway inhibitors and trying new strategies to improve outcomes for men with aggressive, localized disease.
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Tumor environment players in advanced prostate cancer spread
Researchers are studying how the tissue around prostate tumors helps cancer spread, in men with high-risk disease.
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Integrated genomic and AI pathology biomarkers to guide high-risk prostate cancer treatment
A prostate cancer research project tests how genomic and AI-based pathology tools can help tailor who should receive added ARSI therapy with standard radiotherapy and hormone treatment.
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Mitochondrial changes in high-risk prostate cancer
This project looks at changes in mitochondrial DNA and cell energy systems in men, especially African American men, with high‑risk prostate cancer to find markers that predict who will develop aggressive disease.
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Understanding mitochondrial changes in high-risk prostate cancer
This study is looking at how changes in mitochondrial DNA might affect prostate cancer in African American men, who are more likely to face serious cases, with the hope of finding ways to predict and improve treatment for those at risk.
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How high-risk prostate tumors and nearby cells kick off cancer spread
This project looks at how high-risk prostate tumors and the immune and support cells around them start to spread by using advanced scans and detailed analysis of removed prostate tissue.
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.