RNA Polymerase II as a Therapeutic Target in AML with RAS Activation
Official title: RNA Polymerase II as a Therapeutic Target in Acute Myeloid Leukemia (AML) with RAS Signaling Activation
Funded at University of California, San Francisco · NIH-11353945 · Data updated 2026-11-12
This project explores a new way to treat a common type of blood cancer (AML) by blocking a key machinery (RNA Polymerase II) that cancer cells use when the RAS signaling pathway is overactive.
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, 2022 |
| Project end | June 30, 2027 |
| Funding year | 2026 |
| Award (this year) | $547,180 |
| NIH project number | 5R01CA266422-05 |
| Project ID | NIH-11353945 on NIH RePORTER |
Who could benefit from this research
✓Could help
Adults with AML showing RAS/MAPK activation or FLT3-mutant AML who are candidates for targeted therapies.
✕Less likely to help
Patients without RAS/MAPK activation or FLT3-associated resistance mechanisms may see no direct benefit.
What this research studies
If you or a loved one has AML with RAS pathway activation, this research will test whether inhibiting the Mediator/RNA Pol II pathway can make FLT3 inhibitors work longer and better. Scientists will identify which parts of the RNA Pol II system are essential for resistance to treatment and will test existing RNA Pol II inhibitors in lab models that mirror MAPK-activated AML. They will study how RNA Pol II–dependent transcription changes when MAPK signaling and FLT3 inhibition occur, using both preclinical models and patient samples. The goal is to validate downstream targets that drive resistance and to evaluate whether targeting RNA Pol II could be a viable new treatment strategy for this AML subtype.
Why it matters
Potential benefit: If successful, this approach could enhance the effectiveness of existing AML therapies in patients with RAS/MAPK-driven resistance.
How similar studies have gone: Prior work suggests transcriptional programs linked to RNA Pol II can influence drug resistance, supporting potential benefit of this approach, though this exact strategy is being tested in AML with RAS activation.
Where this research is happening
-
University of California, San Francisco
San Francisco, United States Active
Researchers
- Principal investigator: Smith, Catherine Choy — University of California, San Francisco
- Study coordinator: Smith, Catherine Choy
Related research
Other NIH-funded projects on the same topics.
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Acute Myeloid Leukemia: Improving Targeted Therapies through Genetically Defined PDX Models
Researchers are using patient-like leukemia models to develop therapies that target specific genetic features of AML to improve survival.
-
A broader genomic risk picture to guide AML treatment
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SHP2 and BCL2 inhibitors together for AML growth and resistance
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Targeting RNA polymerase II in AML with RAS pathway activation
This project tests drugs that block RNA polymerase II to help people whose acute myeloid leukemia has RAS pathway activation and is resistant to FLT3 inhibitors.
-
New treatment approach for myelodysplastic syndrome and acute myeloid leukemia
This project aims to develop a new antibody-based therapy to help people with MDS or AML, especially older or frail patients who cannot tolerate high-dose chemotherapy.
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Making genetic risk predictions more accurate for adults with acute myeloid leukemia
This project is developing better genetic-based risk categories to help guide treatment decisions for adults with acute myeloid leukemia.
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.