Blocking neddylation to boost irinotecan effects in colorectal cancer
Investigating the role of neddylation in the repair of topoisomerase I inhibitor-induced replication damage in colorectal cancer
This work sees if drugs that block neddylation can stop colorectal cancer cells from repairing damage caused by irinotecan, potentially making the chemotherapy work better.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Maryland Baltimore NIH-funded |
| Lab location | 1 site (Baltimore, United States) |
| Project ID | NIH-11285358 on NIH RePORTER |
What this research studies
Researchers will study how colorectal cancer cells repair DNA damage caused by topoisomerase I inhibitors like irinotecan and why some tumors survive treatment. In lab models they found that blocking neddylation with a drug called pevonedistat prevents the removal of trapped TOP1 protein-DNA lesions and makes cancer cells more sensitive to irinotecan. The team will focus on the CRL4 ubiquitin ligase and a partner protein called DCAF13 to understand how TOP1 is tagged for degradation. Results will guide whether combining a neddylation blocker with TOP1-targeting chemotherapy could be a promising approach.
Who could benefit from this research
Good fit: Ideal candidates are people with colorectal cancer—especially those receiving or planned to receive irinotecan-based chemotherapy—who might later join combination-treatment trials or donate tumor samples for study.
Not a fit: People without colorectal cancer, or whose tumors do not rely on TOP1-related repair pathways, are unlikely to see direct benefit from this work.
Why it matters
Potential benefit: If successful, this could lead to combination treatments that make irinotecan kill more tumor cells and improve responses for people with colorectal cancer.
How similar studies have performed: Early laboratory studies, including work with pevonedistat, have shown promising synergy with TOP1 inhibitors, but this strategy remains largely unproven in patients.
Where this research is happening
Baltimore, United States
- University of Maryland Baltimore — Baltimore, United States (Active)
Researchers
- Principal investigator: Sun, Yilun — University of Maryland Baltimore
- Study coordinator: Sun, Yilun
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.