Targeting And-1 to overcome hormonal therapy resistance in ER-positive breast cancer
The role of And-1 in R-loop and endocrine resistance in breast cancer
Researchers are testing drugs that block a protein called And-1 to help people with ER-positive breast cancer whose tumors stopped responding to aromatase inhibitors.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | George Washington University NIH-funded |
| Lab location | 1 site (Washington, United States) |
| Project ID | NIH-11248754 on NIH RePORTER |
What this research studies
They will study how the protein And-1 helps cancer cells manage unusual DNA structures called R-loops that can turn on the estrogen receptor gene linked to drug resistance. In lab dishes and animal models, the team will use cell tests and mouse experiments to see how blocking And-1 affects tumor growth. The project uses high-throughput and computer-based drug screens that already found promising And-1 inhibitors and will test those compounds in patient-derived tumor grafts and syngeneic models. The goal is to find a strategy that can restore sensitivity to aromatase inhibitors in tumors with ESR1 changes.
Who could benefit from this research
Good fit: Ideal candidates are people with ER-positive breast cancer whose disease no longer responds to aromatase inhibitors, especially tumors with ESR1 mutations or who can provide tumor samples for research.
Not a fit: People with non–ER-positive breast cancers (for example, triple-negative breast cancer) or those whose tumors are not driven by ESR1 changes are unlikely to benefit from this approach.
Why it matters
Potential benefit: If successful, this work could lead to new treatments that help people with ESR1-mutant, aromatase-inhibitor–resistant ER-positive breast cancer respond again to hormonal therapy.
How similar studies have performed: Targeting tumor-specific DNA repair or replication proteins has shown promise in preclinical work, but using And-1 inhibitors specifically to reverse AI resistance is a newer and largely preclinical approach.
Where this research is happening
Washington, United States
- George Washington University — Washington, United States (Active)
Researchers
- Principal investigator: Zhu, Wenge — George Washington University
- Study coordinator: Zhu, Wenge
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.