How loss of ZNF397 leads to TET2-driven therapy resistance in prostate cancer
Deciphering the Impact of ZNF397-deficiency in Promoting TET2-driven Epigenetic Rewiring, Lineage Plasticity, and Therapy Resistance in Prostate Cancer
This project is looking at whether blocking TET2 can stop prostate cancers that lose the ZNF397 protein from becoming resistant to hormone (androgen receptor) therapies.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Yale University NIH-funded |
| Lab location | 1 site (New Haven, United States) |
| Project ID | NIH-11086140 on NIH RePORTER |
What this research studies
From a patient perspective, researchers will study tumor samples and lab models to see how losing the protein ZNF397 lets prostate cancer cells change identity and escape standard hormone treatments. They will compare tumors with and without ZNF397 loss to find molecular signs of this switch and to measure how common it is in patients. The team will test genetic and drug methods to block TET2 in laboratory and preclinical models to see if resistance to AR-targeted therapies can be reversed. The goal is to identify biomarkers and treatment strategies that could be brought into clinical testing for advanced prostate cancer.
Who could benefit from this research
Good fit: Ideal candidates for follow-up clinical efforts would be people with advanced or metastatic prostate cancer—especially those whose tumors show low or absent ZNF397 expression or who have developed resistance to AR-directed therapies.
Not a fit: Patients with early-stage prostate cancer, or whose tumors use different resistance mechanisms unrelated to ZNF397/TET2, may not benefit from findings targeting this pathway.
Why it matters
Potential benefit: If successful, this work could point to new treatments that restore sensitivity to androgen-targeted therapies or identify patients who need different approaches.
How similar studies have performed: Preclinical work suggests blocking TET2 can reverse therapy resistance in models, but targeting this mechanism in patients is largely novel and not yet proven clinically.
Where this research is happening
New Haven, United States
- Yale University — New Haven, United States (Active)
Researchers
- Principal investigator: Mu, Ping — Yale University
- Study coordinator: Mu, Ping
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.