Making pancreatic cancer treatments work better by targeting TNF-alpha signaling
Harnessing TNFa Signaling To Improve Therapeutic Response In Pancreatic Cancer
Researchers are trying a drug combination that blocks TNF-alpha–related signals alongside MAPK pathway drugs to better kill pancreatic cancer cells in people with pancreatic ductal adenocarcinoma.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Washington University NIH-funded |
| Lab location | 1 site (Saint Louis, United States) |
| Project ID | NIH-11285172 on NIH RePORTER |
What this research studies
From my perspective as a patient, the team is focused on pancreatic ductal adenocarcinoma (PDAC), a cancer that often has KRAS mutations. In the lab they found that blocking the MAPK pathway triggers release of TNF-alpha, which can help some cancer cells survive, and they are testing drugs that block a downstream protein called MK2 together with ERK (MAPK) inhibitors. They use 3-D co-culture models that include cancer cells and nearby fibroblasts to see if the drug combination can overcome the protective neighborhood around tumors, and they study immune changes that might make checkpoint immunotherapy work better. The goal is to generate data that could support moving these combinations into clinical trials for patients with PDAC.
Who could benefit from this research
Good fit: Ideal candidates would be people with pancreatic ductal adenocarcinoma, especially those with tumors driven by KRAS who have limited response to current therapies.
Not a fit: People without PDAC, or whose tumors do not rely on the MAPK/TNF-alpha pathways or who cannot tolerate targeted or immune-based treatments, are unlikely to benefit directly from these findings.
Why it matters
Potential benefit: If successful, this work could lead to new combination treatments that make current targeted drugs and immunotherapies work better for people with pancreatic cancer.
How similar studies have performed: Direct targeting of KRAS/MAPK has had limited clinical success due to resistance, so this MK2-plus-ERK approach is relatively novel with encouraging preclinical results but not yet proven in patients.
Where this research is happening
Saint Louis, United States
- Washington University — Saint Louis, United States (Active)
Researchers
- Principal investigator: Lim, Kian H — Washington University
- Study coordinator: Lim, Kian H
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.