Targeting mTORC1 to treat fusion-positive rhabdomyosarcoma in children
Official title: Targeting mTORC1 translational control in FOXO1 fusion positive rhabdomyosarcoma
Funded at University of California, San Francisco · NIH-11357692 · Data updated 2026-11-12
Aims to slow or stop the cancer-causing activity of PAX3-FOXO1 in childhood rhabdomyosarcoma by using a new class of drugs that block protein production at the start of protein-making.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of California, San Francisco NIH-funded |
| Lab location | 1 site (San Francisco, United States) |
| Project start | July 1, 2024 |
| Project end | June 30, 2029 |
| Funding year | 2026 |
| Award (this year) | $490,522 |
| NIH project number | 5R01CA285680-03 |
| Project ID | NIH-11357692 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates are children and adolescents with fusion-positive rhabdomyosarcoma or related RMS that express PAX3-FOXO1.
✕Less likely to help
Patients with RMS that do not involve PAX3-FOXO1 fusion or who have already progressed on similar mTORC1 inhibitors may be less likely to benefit.
What this research studies
This project focuses on a childhood cancer called fusion-positive rhabdomyosarcoma, where a genetic driver called PAX3-FOXO1 makes cancer cells grow. The researchers have found that the mTORC1 pathway, which helps cells make proteins, is essential for this driver and can be targeted with third-generation bi-steric inhibitors like RMC-6272. They will study how blocking cap-dependent translation affects the cancer and why resistance occurs, with the goal of designing combinations that improve durability of responses. The work combines molecular analyses, informatics, and proteomics to uncover why PAX3-FOXO1 depends on cap-dependent translation and how to use that knowledge clinically. Overall, the study aims to inform safer and more effective use of bi-steric mTORC1 inhibitors in kids with this disease.
Why it matters
Potential benefit: If successful, this approach could lead to durable treatments that specifically disrupt the cancer-driving mechanism in fusion-positive RMS, potentially improving cure rates for children.
How similar studies have gone: Previous PDX studies show that bi-steric mTORC1 inhibitors can induce remissions, but resistance develops, highlighting the need for combination strategies.
Where this research is happening
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University of California, San Francisco
San Francisco, United States Active
Researchers
- Principal investigator: Sabnis, Amit J. — University of California, San Francisco
- Study coordinator: Sabnis, Amit J.
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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.