Stopping therapy-resistant prostate cancer by blocking FOXA2 and AP-1
Official title: Targeting FOXA2/AP-1 axis to overcome lineage plasticity and therapy resistance in castration-resistant prostate cancer
Funded at University of Massachusetts Boston · NIH-11404787 · Data updated 2026-11-12
This research looks at whether blocking a protein switch called FOXA2 and its partner AP‑1 can stop or reverse prostate cancers that no longer respond to hormone therapy.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Massachusetts Boston NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project start | February 21, 2025 |
| Project end | January 31, 2030 |
| Funding year | 2026 |
| Award (this year) | $418,610 |
| NIH project number | 5R01CA299202-02 |
| Project ID | NIH-11404787 on NIH RePORTER |
Who could benefit from this research
✓Could help
Men with advanced castration‑resistant prostate cancer, particularly those whose tumors have become AR‑indifferent or show neuroendocrine features or lineage plasticity, would be the most relevant group.
✕Less likely to help
Patients with early‑stage, hormone‑sensitive prostate cancer or those without prostate cancer are unlikely to see direct benefits from this primarily laboratory research in the short term.
What this research studies
Researchers will examine tumor samples and laboratory models to understand how FOXA2 helps prostate cancer cells change identity and escape hormone treatments. They will map where FOXA2 and AP‑1 bind DNA, study how the enzyme LSD1 stabilizes FOXA2 on chromatin, and test ways to disrupt this pathway in cell lines and animal models. The goal is to find molecular targets that could lead to new treatments for men with castration‑resistant, AR‑indifferent prostate cancer.
Why it matters
Potential benefit: If successful, this could reveal new drug targets to prevent or reverse resistance to androgen‑targeted therapies in advanced prostate cancer.
How similar studies have gone: Prior laboratory studies support roles for FOXA family proteins, AP‑1, and LSD1 in prostate cancer plasticity, but directly targeting the FOXA2/AP‑1 interaction is largely experimental and has not been tested in patients.
Where this research is happening
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University of Massachusetts Boston
Boston, United States Active
Researchers
- Principal investigator: Cai, Changmeng — University of Massachusetts Boston
- Study coordinator: Cai, Changmeng
Related research
Other NIH-funded projects on the same topics.
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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.
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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.
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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.
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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.
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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.
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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.