How a cell stress pathway and nerve changes cause cisplatin resistance and spread in head and neck cancer
Official title: Defining the role of KEAP/NRF2 signaling dysregulation and sensory nerve reprograming during acquisition of cisplatin resistance and metastasis in HNSCC
Funded at University of Tx Md Anderson Can Ctr · NIH-11182531 · Data updated 2026-11-12
Scientists are targeting the NRF2 stress pathway and tumor-associated nerve changes to try to overcome cisplatin resistance in people with head and neck cancer.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Tx Md Anderson Can Ctr NIH-funded |
| Lab location | 1 site (Houston, United States) |
| Project start | September 20, 2022 |
| Project end | August 31, 2027 |
| Funding year | 2025 |
| Award (this year) | $195,369 |
| NIH project number | 5U54CA274321-04 |
| Project ID | NIH-11182531 on NIH RePORTER |
Who could benefit from this research
✓Could help
People with head and neck squamous cell carcinoma, particularly those who have relapsed or whose tumors no longer respond to cisplatin, are the most relevant candidates.
✕Less likely to help
Patients without head and neck cancer, those cured with first-line therapy who never develop resistance, or tumors that lack NRF2/KEAP1-related changes may not benefit from these findings.
What this research studies
I learned that tumors of the head and neck often become resistant to cisplatin, so the team made lab models from different tumor lines to copy that problem. They discovered many resistant cells turn on the NRF2 pathway because of KEAP1 changes and are testing a drug that blocks glutaminase 1 to lower glutathione and reverse resistance. At the same time they study how sensory nerves around tumors are reprogrammed and may help cancer spread. The work uses genomic tools like CRISPR libraries and cell and nerve models to point toward therapies that could make chemotherapy work again.
Why it matters
Potential benefit: If successful, this work could restore cisplatin sensitivity and reduce metastasis, making chemotherapy more effective for people with head and neck cancer.
How similar studies have gone: Preclinical studies targeting NRF2-related metabolism and using glutaminase inhibitors have shown promise in reversing resistance, but clinical proof in patients remains limited.
Where this research is happening
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University of Tx Md Anderson Can Ctr
Houston, United States Active
Researchers
- Principal investigator: Osman, Abdullah Ali — University of Tx Md Anderson Can Ctr
- Study coordinator: Osman, Abdullah Ali
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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.