New drugs that trigger a fast, immune-activating death in ER-positive and metastatic cancers
A Pathway for Necrotic Cell Death
Researchers are developing drugs that force ER-positive cancer cells to swell and die in a way that can also activate the immune system, aiming to help people with therapy-resistant and metastatic cancers.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Illinois at Urbana-Champaign NIH-funded |
| Lab location | 1 site (Champaign, United States) |
| Project ID | NIH-11137794 on NIH RePORTER |
What this research studies
This project studies how two experimental drugs, BHPI and ErSO, act through the estrogen receptor (ERα) to cause a rapid, necrotic form of cancer cell death. Lab work shows the drugs raise calcium levels that open a cell-surface channel (TRPM4), causing sodium and water to rush in, swelling the cells, triggering stress responses and membrane rupture. The team uses cell models, patient-derived tumor samples, patient malignant ascites, and animal tumor models (including orthotopic xenografts and PDXs) to test how blocking or activating TRPM4 changes drug effects. The goal is to understand the mechanism well enough to improve drug design and potentially boost immune responses against resistant and metastatic tumors, including brain and ovarian disease.
Who could benefit from this research
Good fit: The most likely candidates would be people with estrogen receptor–positive (ERα+) cancers that are therapy-resistant or have metastasized, including breast, endometrial, and ovarian cancers and patients with tumor cells in malignant ascites.
Not a fit: Patients whose tumors do not express estrogen receptor α or whose cancers are driven by unrelated mechanisms are unlikely to benefit from these drugs.
Why it matters
Potential benefit: If this work translates to people, it could offer a new way to kill therapy-resistant ERα+ cancers and help the immune system clear metastatic tumors.
How similar studies have performed: Preclinical studies in animal models and patient-derived tumor samples have shown promising tumor regressions with ErSO and BHPI, but these approaches remain experimental and need clinical testing in people.
Where this research is happening
Champaign, United States
- University of Illinois at Urbana-Champaign — Champaign, United States (Active)
Researchers
- Principal investigator: Shapiro, David J — University of Illinois at Urbana-Champaign
- Study coordinator: Shapiro, David J
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.