Targeting ERK’s brake pedals to slow cancer progression
Official title: Divergent Functions of ERK Substrate Binding Domains in Pathogenesis of Myeloproliferative Neoplasms
Funded at Research Inst of Fox Chase Can Ctr · NIH-11364927 · Data updated 2026-11-12
Aims to block the parts of ERK signaling that speed up cancer progression, by guiding drugs to the substrate-binding domains that act like accelerator pedals in myeloproliferative neoplasms and related cancers.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Research Inst of Fox Chase Can Ctr NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project start | July 6, 2023 |
| Project end | June 30, 2028 |
| Funding year | 2026 |
| Award (this year) | $708,730 |
| NIH project number | 5R01CA283396-04 |
| Project ID | NIH-11364927 on NIH RePORTER |
Who could benefit from this research
✓Could help
Patients with myeloproliferative neoplasms or related cancers driven by Ras/MAPK signaling may be eligible for future trials.
✕Less likely to help
If a patient’s cancer is not driven by ERK substrate interactions, they may not benefit from this approach.
What this research studies
This project focuses on the Ras/MAPK pathway, which is overactive in many cancers, and seeks a new way to modulate it by directing kinase activity toward “brake pedal” substrates rather than shutting down the enzyme entirely. By studying ERK2’s D and DPB substrate-binding domains, researchers hope to design inhibitors that redirect activity away from promoting disease. The work combines molecular studies with approaches that could inform future therapies for blood cancers linked to FLT3/JAK2 signaling and related pathways. If successful, these ideas could lead to drugs that better control cancer growth with potentially fewer side effects than broad kinase inhibitors.
Why it matters
Potential benefit: If successful, patients could benefit from new therapies that more precisely slow cancer progression by rerouting ERK activity.
How similar studies have gone: Preliminary data indicate that ERK2’s D-domain and DPB-domain have opposing roles, supporting a novel, potentially effective strategy.
Where this research is happening
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Research Inst of Fox Chase Can Ctr
Philadelphia, United States Active
Researchers
- Principal investigator: Wiest, David L. — Research Inst of Fox Chase Can Ctr
- Study coordinator: Wiest, David L.
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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.