Understanding how cancer drugs can sometimes activate BRAF proteins
Allosteric mechanisms driving paradoxical activation of RAF kinases
This project aims to understand why some new cancer medicines for melanoma, thyroid, and colon cancers can unexpectedly make the cancer-driving BRAF protein more active.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Minnesota NIH-funded |
| Lab location | 1 site (Minneapolis, United States) |
| Project ID | NIH-11124123 on NIH RePORTER |
What this research studies
This project focuses on BRAF mutations, which are common in melanoma, thyroid, and colon cancers. While initial treatments work well, cancer cells often become resistant because the BRAF protein changes its shape and forms pairs, making drugs less effective. Newer drugs try to target these paired BRAF proteins, but sometimes they accidentally make the BRAF protein even more active, which is called "paradoxical activation." Our team is using advanced lab techniques to build a detailed model that explains how these drugs cause BRAF proteins to pair up and become more active, helping us design better treatments.
Who could benefit from this research
Good fit: This foundational laboratory research is relevant for patients with BRAF-mutated cancers, such as melanoma, thyroid cancer, and colon cancer, who may experience drug resistance.
Not a fit: Patients whose cancers do not involve BRAF mutations or those not experiencing resistance to current BRAF inhibitors would not directly benefit from this specific research.
Why it matters
Potential benefit: If successful, this work could lead to the design of new, more effective cancer drugs that avoid paradoxical activation and overcome drug resistance in patients with BRAF-mutated cancers.
How similar studies have performed: Existing drugs targeting BRAF have shown initial success, but the phenomenon of paradoxical activation with newer inhibitors is a known challenge that this project seeks to address with a novel mechanistic approach.
Where this research is happening
Minneapolis, United States
- University of Minnesota — Minneapolis, United States (Active)
Researchers
- Principal investigator: Levinson, Nicholas Mark — University of Minnesota
- Study coordinator: Levinson, Nicholas Mark
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 below.