Targeting DNA repair weaknesses in leiomyosarcoma
Official title: PROJECT 1: Genomic Vulnerabilities in Leiomyosarcoma (LMS)
Funded at University of Michigan at Ann Arbor · NIH-11193258 · Data updated 2026-11-12
This project tests drugs that block a DNA-repair enzyme to make leiomyosarcoma tumors more sensitive to treatment for people with metastatic LMS.
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 | 2025 |
| Award (this year) | $423,362 |
| NIH project number | 5P50CA272170-04 |
| Project ID | NIH-11193258 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates are people with leiomyosarcoma—especially those with metastatic disease—who can provide tumor biopsies or samples and attend follow-up visits.
✕Less likely to help
People without leiomyosarcoma, or whose tumors lack DNA-repair defects or chromosomal instability, are unlikely to benefit directly from these approaches.
What this research studies
From a patient's perspective, researchers are looking at why many leiomyosarcoma tumors have unstable chromosomes and rely on a DNA-repair enzyme called DNA-PK. They will compare tumor samples from different metastases and measure DNA-PK activity, DNA damage markers, and specific gene changes (like TP53 and RB1). The team plans to see whether partial versus complete TP53 changes affect how tumors respond to DNA-PK targeting. Ultimately they want to find better ways to pick patients and design treatments that push the cancer past its ability to repair itself.
Why it matters
Potential benefit: If successful, this work could lead to treatments that make leiomyosarcoma more responsive to therapy and reduce the chance of deadly metastasis.
How similar studies have gone: Similar strategies targeting DNA-repair weaknesses (for example PARP inhibitors in other cancers) have shown benefit, but directly targeting DNA-PK in leiomyosarcoma is a newer, early-stage approach.
Where this research is happening
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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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Genomic vulnerabilities in leiomyosarcoma: targeting DNA-PK pathways
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.
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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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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.