Mouse and organoid models that mimic highly-mutated bowel cancer
Polymerase epsilon-based mouse and derived organoid models of intestinal cancer
This project creates mouse and lab-grown organoids that copy human intestinal cancers with very high mutation rates so researchers can learn how those tumors grow and respond to treatments.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Ut Southwestern Medical Center NIH-funded |
| Lab location | 1 site (Dallas, United States) |
| Project ID | NIH-11164518 on NIH RePORTER |
What this research studies
Researchers will engineer mice with a specific POLE mutation that causes ultramutation in human intestinal cancers and grow matching organoids in the lab. They will study how these tumors develop, how diverse the cancer cells become, and how the immune system interacts with them. The team will use the models to test responses to immune-based and other therapies and to explore mechanisms of treatment resistance. By reproducing the high mutation patterns seen in some patients, these models aim to make preclinical testing more predictive for future therapies.
Who could benefit from this research
Good fit: People with colorectal or intestinal cancer—especially those whose tumors have POLE mutations or very high mutation burdens—or patients willing to donate tumor tissue would be most relevant to this work.
Not a fit: Patients with cancers outside the intestine or with bowel cancers driven by different, low-mutation genetic changes are unlikely to see direct benefits from this project.
Why it matters
Potential benefit: If successful, this work could speed development of better-targeted and immune-based treatments for people with highly-mutated bowel cancers.
How similar studies have performed: Animal and organoid models have previously aided research on common bowel cancer pathways and high-mutation tumors in patients often respond to immunotherapy, but POLE-driven ultramutation models are relatively novel and less tested.
Where this research is happening
Dallas, United States
- Ut Southwestern Medical Center — Dallas, United States (Active)
Researchers
- Principal investigator: Castrillon, Diego H — Ut Southwestern Medical Center
- Study coordinator: Castrillon, Diego 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.