How PRMT5 helps cancers that lack the MTAP gene
The function of the PRMT5 methylosome in MTAP deleted cancers
This project aims to find better treatments for people whose tumors have lost the MTAP gene by targeting a protein called PRMT5.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Broad Institute, INC. NIH-funded |
| Lab location | 1 site (Cambridge, United States) |
| Project ID | NIH-11246354 on NIH RePORTER |
What this research studies
From a patient's point of view, the team will use advanced lab tools and genetic screens to see why cancers missing MTAP are especially dependent on PRMT5 and why they sometimes stop responding to PRMT5-targeting drugs. They will test cancer cells and animal models, study tumor and surrounding tissues, and use data from early human trials to guide their work. The researchers will look for genes and pathways that cause resistance and search for drug combinations that keep tumors shrinking. Their findings are meant to point toward combination therapies that could move into future clinical trials.
Who could benefit from this research
Good fit: People with cancers (for example pancreatic, esophageal, or lung) whose tumors have lost the MTAP gene and often the nearby CDKN2A gene are the most relevant candidates.
Not a fit: Patients whose tumors do not have MTAP loss or whose cancers are driven by unrelated mechanisms are unlikely to benefit from PRMT5-targeted approaches.
Why it matters
Potential benefit: If successful, this work could identify drug combinations that make PRMT5-targeted treatments work better and longer for MTAP-deleted cancers.
How similar studies have performed: Early phase I trials of MTAP-cooperative PRMT5 inhibitors have shown tumor responses and acceptable safety, but resistance has already been observed and needs new combination strategies.
Where this research is happening
Cambridge, United States
- Broad Institute, INC. — Cambridge, United States (Active)
Researchers
- Principal investigator: Sellers, William R — Broad Institute, INC.
- Study coordinator: Sellers, William R
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.