Genomic vulnerabilities in leiomyosarcoma: targeting DNA-PK pathways
Official title: PROJECT 1: Genomic Vulnerabilities in Leiomyosarcoma (LMS)
Funded at University of Michigan at Ann Arbor · NIH-11419787 · Data updated 2026-11-12
This grant aims to find targeted ways to treat leiomyosarcoma by exploiting the tumor’s DNA repair weaknesses and testing biomarkers that may guide therapy.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Michigan at Ann Arbor NIH-funded |
| Lab location | 1 site (Ann Arbor, United States) |
| Project start | September 16, 2022 |
| Project end | August 31, 2027 |
| Funding year | 2026 |
| Award (this year) | $462,618 |
| NIH project number | 5P50CA272170-05 |
| Project ID | NIH-11419787 on NIH RePORTER |
Who could benefit from this research
✓Could help
Patients with leiomyosarcoma, especially those with metastases, could potentially benefit from advances in DNA-PK–targeted therapies.
✕Less likely to help
Patients whose tumors do not rely on DNA-PK pathways or who cannot tolerate the proposed therapies may not benefit.
What this research studies
Leiomyosarcoma is a common and hard-to-treat cancer where half of patients develop metastases. The project explores how genetic instability in LMS creates a dependency on DNA-PK, a DNA repair enzyme, and seeks therapies that intensify DNA damage in tumors. Researchers will test biomarkers to see how metastases from the same patient respond and whether different TP53 mutations change treatment signals. The work involves analyzing tumor samples and testing targeted approaches to disrupt the DNA-PK pathway to push cancer cells past their repair limits. If successful, this could point to new, more selective treatments for LMS patients.
Why it matters
Potential benefit: Potentially more effective, targeted therapies for LMS that exploit tumor DNA repair weaknesses.
How similar studies have gone: Prior work has linked CIN and DNA-PK pathway dependence to cancer therapy sensitivity, supporting a translational path for LMS.
Where this research is happening
-
University of Michigan at Ann Arbor
Ann Arbor, United States Active
Researchers
- Principal investigator: Fletcher, Jonathan Alfred — University of Michigan at Ann Arbor
- Study coordinator: Fletcher, Jonathan Alfred
Related research
Other NIH-funded projects on the same topics.
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Leiomyosarcoma treatment insights from tumor genetics
A study looks at how tumor genetics relate to how leiomyosarcoma patients respond to standard systemic therapies.
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Genetics and Genomics of Leiomyosarcoma: better understanding and new options for diagnosis and treatment
A large research program is exploring the genetic drivers of leiomyosarcoma to help develop better ways to diagnose and treat this cancer.
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Targeting DNA repair weaknesses in leiomyosarcoma
This project tests drugs that block a DNA-repair enzyme to make leiomyosarcoma tumors more sensitive to treatment for people with metastatic LMS.
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Understanding the genes behind leiomyosarcoma to improve diagnosis and treatment
This project looks at how inherited and tumor gene changes, especially TP53 and other DNA repair genes, affect people with leiomyosarcoma to help create better tests and therapies.
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Developing a new mouse model for a rare type of uterine cancer
This study is creating special mice that have a type of uterine cancer called leiomyosarcoma, so researchers can learn more about the disease and find better treatments for people who have it.
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Understanding genetic weaknesses in leiomyosarcoma
This study is looking at leiomyosarcoma, a tough type of cancer, to understand how certain genetic changes can affect how it responds to treatment, with the goal of finding better ways to target and treat this cancer for patients like you.
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.