Boosting cetuximab response in oral cancer by targeting mitochondrial complex I
Inhibiting mitochondrial complex I to improve cetuximab efficacy in oral cancer
['FUNDING_R01'] · EMORY UNIVERSITY · NIH-11322613
This work tries adding a drug that blocks a mitochondrial enzyme to help cetuximab work better for people with oral squamous cell carcinoma.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | EMORY UNIVERSITY (nih funded) |
| Locations | 1 site (ATLANTA, UNITED STATES) |
| Trial ID | NIH-11322613 on ClinicalTrials.gov |
What this research studies
Researchers are using lab-grown oral cancer cells and a mouse model that carries human EGFR to see whether a pill called IACS-010759, which blocks mitochondrial complex I, can make cetuximab kill more tumor cells. They used a genome-wide CRISPR screen to find that TNFα signaling helps tumors survive cetuximab and found that IACS redirects that signal to trigger inflammatory cell death (pyroptosis) via ROS and gasdermin D. The team also examines how CD8+ T cells contribute to tumor remission when the two drugs are combined. These preclinical experiments aim to generate evidence that could support future clinical testing of the combination in patients.
Who could benefit from this research
Good fit: Ideal candidates would be adults with EGFR-expressing oral squamous cell carcinoma who are eligible for cetuximab therapy or have tumors that are resistant to it.
Not a fit: People whose tumors do not express EGFR, who cannot tolerate mitochondrial complex I inhibitors, or who have unrelated serious health issues may not benefit from this approach.
Why it matters
Potential benefit: If successful, this approach could make cetuximab effective for more people with oral squamous cell carcinoma and stimulate immune-mediated tumor clearance.
How similar studies have performed: Mitochondrial complex I inhibitors like IACS-010759 have shown anti-cancer activity in laboratory and animal studies, but combining them with cetuximab for oral cancer is a novel, mostly preclinical strategy.
Where this research is happening
ATLANTA, UNITED STATES
- EMORY UNIVERSITY — ATLANTA, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: TENG, YONG — EMORY UNIVERSITY
- Study coordinator: TENG, YONG
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.