Targeting RNA polymerase II in AML with RAS pathway 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-11210635 · Data updated 2026-11-12
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.
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 | 2025 |
| Award (this year) | $77,113 |
| NIH project number | 3R01CA266422-04S1 |
| Project ID | NIH-11210635 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates are people with acute myeloid leukemia, especially those with FLT3 mutations and evidence of RAS/MAPK pathway activation or relapse after FLT3 inhibitor therapy.
✕Less likely to help
Patients whose leukemia lacks RAS/MAPK activation or who cannot provide samples or participate in follow-up studies are less likely to benefit directly from this project.
What this research studies
You would be part of work where researchers test existing RNA polymerase II pathway inhibitors in lab models and in leukemia samples from patients to see if these drugs can overcome resistance driven by RAS/MAPK signaling. The team will pinpoint which parts of the Mediator/RNA Pol II system are most important for resistance and then confirm the key genes that allow leukemia cells to survive. They will combine studies in cell and animal models with analyses of patient samples to guide which therapies look most promising. Successful findings would be used to design future clinical trials that patients with resistant AML might join.
Why it matters
Potential benefit: If successful, this could lead to new treatments that overcome resistance to FLT3 inhibitors for patients with RAS-activated AML.
How similar studies have gone: Related approaches targeting transcriptional machinery have shown encouraging preclinical activity but remain early and are not yet standard clinical care.
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.
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A broader genomic risk picture to guide AML treatment
AIM to refine how genetic information guides treatment decisions for adults with acute myeloid leukemia by looking at how inherited and recurrent mutations affect risk.
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RNA Polymerase II as a Therapeutic Target in AML with RAS Activation
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.
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SHP2 and BCL2 inhibitors together for AML growth and resistance
A patient-focused look at whether combining SHP2 inhibitors with a BCL2 inhibitor can slow or stop AML, especially in people whose disease has FLT3 or KIT mutations.
-
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.