Blocking cancer cell recycling in KRAS-mutant pancreatic cancer
Official title: Project 1: Targeting autophagy for the treatment of KRAS-mutant PDAC
Funded at Univ of North Carolina Chapel Hill · NIH-11196737 · Data updated 2026-11-12
This project is trying to combine drugs that block cancer growth signals with hydroxychloroquine to help people with KRAS-mutant pancreatic cancer respond better to treatment.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Univ of North Carolina Chapel Hill NIH-funded |
| Lab location | 1 site (Chapel Hill, United States) |
| Project start | September 16, 2022 |
| Project end | August 31, 2027 |
| Funding year | 2025 |
| Award (this year) | $448,515 |
| NIH project number | 5P50CA257911-04 |
| Project ID | NIH-11196737 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates are people with pancreatic ductal adenocarcinoma whose tumors carry KRAS mutations and who meet standard clinical trial eligibility regarding fitness and organ function.
✕Less likely to help
People with cancers that lack KRAS mutations, those with other tumor types, or patients who are too frail or have medical conditions making the drugs unsafe may not benefit or be eligible.
What this research studies
Researchers found that when KRAS-driven pancreatic tumors are treated with drugs that block the RAF-MEK-ERK growth pathway, the cancer cells increase a recycling process called autophagy to survive. The team is combining ERK/MEK inhibitors with the autophagy blocker hydroxychloroquine to try to cut off that escape route. They have launched clinical trials testing combinations such as trametinib or binimetinib plus hydroxychloroquine and a phase II trial of an ERK inhibitor (LY3214996) plus hydroxychloroquine. The work will follow patients for safety, tumor response, and biological changes in tumor metabolism and autophagy.
Why it matters
Potential benefit: If successful, this approach could make treatments work better against KRAS-mutant pancreatic cancer, potentially shrinking tumors or extending survival.
How similar studies have gone: Preclinical studies and independent labs support the idea that blocking ERK/MEK makes tumors dependent on autophagy, but hydroxychloroquine alone showed limited benefit in pancreatic cancer and the combined treatment approach is still being tested in clinical trials.
Where this research is happening
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Univ of North Carolina Chapel Hill
Chapel Hill, United States Active
Researchers
- Principal investigator: Der, Channing J. — Univ of North Carolina Chapel Hill
- Study coordinator: Der, Channing J.
Related research
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Targeting autophagy to treat KRAS-mutant pancreatic cancer
This grant explores using approved drugs to block autophagy in KRAS-mutant pancreatic cancer to improve treatment outcomes.
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Reprogramming PDAC stroma by targeting blood clotting in the tumor environment
A cancer research grant aimed at turning the tough, fibrous pancreatic cancer environment into one that helps treatments work better and supports the body’s immune response.
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Understanding paracrine signals in pancreatic cancer to improve drug delivery
A patient-focused look at how the tumor’s signaling networks affect treatment delivery in pancreatic cancer and how targeting these networks could help therapies reach tumors more effectively.
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.