Why some ER-positive breast cancers stop responding to CDK4/6 inhibitor drugs
Regulation of resistance to CDK4/6 inhibitor in breast cancer
This project looks at whether a protein sugar tag called O-GlcNAcylation helps ER-positive breast cancers stop responding to CDK4/6 inhibitor drugs and aims to find ways to restore drug sensitivity.
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-11284101 on NIH RePORTER |
What this research studies
Researchers will use high-throughput drug combination screens and lab models of ER-positive (hormone receptor–positive) breast cancer to pinpoint how cells become resistant to CDK4/6 inhibitors. They focus on an enzyme called OGT that adds O-GlcNAc sugar tags to proteins and will study how this modification changes cancer cell behavior and drug response. Work includes detailed molecular experiments in cell lines and follow-up tests of promising drug combinations that reverse resistance. If human tumor samples are used, findings could help guide future clinical trials to test new combination treatments for patients whose tumors stopped responding.
Who could benefit from this research
Good fit: Patients with ER-positive (hormone receptor–positive) advanced or metastatic breast cancer who have received CDK4/6 inhibitors and experienced primary or acquired resistance would be the most relevant candidates.
Not a fit: Patients with non–ER-positive breast cancers (for example triple-negative disease), those not treated with CDK4/6 inhibitors, or whose tumors have different resistance mechanisms may not benefit from findings focused on O-GlcNAcylation.
Why it matters
Potential benefit: Could lead to new combination therapies that help patients with ER-positive breast cancer overcome resistance to CDK4/6 inhibitors.
How similar studies have performed: CDK4/6 inhibitors are already standard for ER-positive advanced breast cancer but resistance is common; targeting O-GlcNAcylation is a relatively new approach with limited prior clinical validation.
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.