Targeting Ref-1 to expose metabolic weaknesses in pancreatic cancer
Metabolic flux analysis and PDX models to understand therapeutic vulnerabilities following inhibition of Ref-1 redox signaling in pancreatic cancer
This project tests drugs that block a protein called Ref-1, alone and in combination, to try to kill pancreatic cancer cells that survive in low-oxygen, stiff tumor environments.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Indiana University Indianapolis NIH-funded |
| Lab location | 1 site (Indianapolis, United States) |
| Project ID | NIH-11211044 on NIH RePORTER |
What this research studies
If you have pancreatic cancer, researchers will work to block a protein called Ref-1 that helps tumors grow and resist treatment, and then watch how the tumor's metabolism changes. They will measure metabolic pathways using metabolic flux analysis and grow 3-D tumor spheroids and patient-derived xenografts (PDX) made from patient tumor samples to test drug combinations. The team is optimizing next-generation Ref-1 inhibitors and plans to screen tumor samples to find which patients are most likely to respond. Promising drug combinations and biomarkers would be moved toward clinical testing.
Who could benefit from this research
Good fit: Ideal candidates would be adults with pancreatic ductal adenocarcinoma, especially those with advanced or treatment-resistant disease whose tumors could be tested for Ref-1 sensitivity.
Not a fit: People without pancreatic cancer or whose tumors do not rely on Ref-1-driven pathways are unlikely to benefit from these specific approaches.
Why it matters
Potential benefit: If successful, this work could lead to new drug combinations or markers that help treat or control pancreatic cancer more effectively.
How similar studies have performed: An earlier phase I trial of the first Ref-1 inhibitor (APX3330) showed some responses and disease stabilization with good safety, but the next-generation inhibitors and combination strategies are still largely preclinical.
Where this research is happening
Indianapolis, United States
- Indiana University Indianapolis — Indianapolis, United States (Active)
Researchers
- Principal investigator: Kelley, Mark R. — Indiana University Indianapolis
- Study coordinator: Kelley, Mark R.
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.