Blocking LSD1 to stop treatment-driven cell changes in BRAF‑mutant colon cancer
Targeting LSD1 to prevent therapy-induced transdifferentiation in BRAF mutant colorectal cancer
This project tests whether blocking a protein called LSD1 can prevent BRAF‑mutant colorectal cancers from changing into a treatment‑resistant cell type during targeted therapy.
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-11286789 on NIH RePORTER |
What this research studies
Some colorectal cancers with BRAF mutations become resistant because cancer cells shift into enteroendocrine‑like cells that survive treatment. The team will study how the enzyme LSD1 controls that cell identity and whether inhibiting LSD1 stops this shift using tumor samples, cell models, and animal models. They will combine BRAF and EGFR inhibitors with LSD1 blockade in the lab to see if tumors remain sensitive. Findings may point to biomarkers or drug combinations that could be tested in patients later.
Who could benefit from this research
Good fit: Patients with metastatic colorectal cancer whose tumors carry the BRAF V600E mutation, especially those receiving or who have received BRAF plus EGFR targeted therapy, would be the most relevant candidates.
Not a fit: People without BRAF‑mutant colorectal cancer or those with early‑stage disease unlikely to receive BRAF‑targeted therapy are unlikely to benefit from this specific approach.
Why it matters
Potential benefit: If successful, this could prevent or delay resistance and extend the effectiveness of BRAF‑targeted therapies for patients with BRAF‑mutant metastatic colorectal cancer.
How similar studies have performed: Targeting lineage plasticity and LSD1 has shown promise in preclinical models and in some other cancers, but applying LSD1 inhibition to prevent therapy‑induced transdifferentiation in BRAF‑mutant colorectal cancer is a novel direction.
Where this research is happening
Indianapolis, United States
- Indiana University Indianapolis — Indianapolis, United States (Active)
Researchers
- Principal investigator: O'hagan, Heather M — Indiana University Indianapolis
- Study coordinator: O'hagan, Heather M
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.