Stopping precancerous mouth lesions from becoming oral cancer by targeting cell-growth signals
Targeting Signaling Vulnerabilities for Oral Cancer Prevention
Using drugs that block the PI3K/mTOR cell-growth pathway — including the diabetes medicine metformin — to try to prevent precancerous mouth lesions from turning into oral cancer in people with those lesions.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of California, San Diego NIH-funded |
| Lab location | 1 site (La Jolla, United States) |
| Project ID | NIH-11311828 on NIH RePORTER |
What this research studies
This work focuses on people with oral premalignant lesions (OPLs) and aims to block a signaling pathway (PI3K/mTOR) that drives progression to head and neck cancer. Researchers combine laboratory studies, genetic CRISPR screens, biomarker analysis of tissue and body fluids, and clinical testing of drugs such as mTOR inhibitors and repurposed metformin. Prior early-phase work showed metformin reduced mTOR signaling and produced a 60% histologic response in OPLs, and this program expands that work across multiple centers. Participants would have lesion sampling and biomarker testing to link drug effects to tissue changes and cancer prevention outcomes.
Who could benefit from this research
Good fit: Adults with diagnosed oral premalignant lesions (OPLs) or otherwise considered at high risk for head and neck squamous cell carcinoma would be the ideal candidates.
Not a fit: People who already have invasive head and neck cancer or whose lesions do not show activation of the PI3K/mTOR pathway are less likely to benefit.
Why it matters
Potential benefit: If successful, this approach could lower the chance that precancerous mouth lesions progress to invasive oral cancer and offer a safe preventive option using existing drugs.
How similar studies have performed: Earlier work, including a Phase IIa trial of metformin in OPLs, showed a 60% histologic response and a correlation with mTOR inhibition, providing promising preliminary evidence but requiring larger confirmation.
Where this research is happening
La Jolla, United States
- University of California, San Diego — La Jolla, United States (Active)
Researchers
- Principal investigator: Gutkind, Jorge Silvio — University of California, San Diego
- Study coordinator: Gutkind, Jorge Silvio
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.