Melanoma resistance atlas to find drug combinations that stop or reverse MAPK therapy resistance
Melanoma Resistance Evolution Atlas (MREA) for identifying combinatorial targets to prevent and reverse MAPKi resistance
Researchers are building a detailed map of how different melanomas become resistant to MAPK-targeting drugs so they can find drug combinations that might prevent or reverse that resistance for more patients.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of California Los Angeles NIH-funded |
| Lab location | 1 site (Los Angeles, United States) |
| Project ID | NIH-11295389 on NIH RePORTER |
What this research studies
The team will collect tumor samples from a wide range of melanoma patients and create patient-derived xenografts and subclones to model how tumors evolve resistance to MAPK inhibitors. They will run proteogenomic analyses (DNA, RNA, and protein) to chart the molecular changes that accompany resistance across BRAFV600-mutant, NRAS-mutant, NF1-null, and triple wildtype melanomas. Laboratory tests will trial combinations that target MAPK pathway reactivation and parallel resistance mechanisms to find therapies that stop or reverse resistance. Promising combinations will be nominated to guide future clinical trials.
Who could benefit from this research
Good fit: Ideal candidates are people with melanoma—especially tumors that are BRAFV600-mutant, NRAS-mutant, NF1-null, or triple wildtype—who can provide tumor tissue or consider joining future clinical trials.
Not a fit: Patients whose tumors do not depend on the MAPK pathway, or who cannot provide tissue or access participating sites, are less likely to benefit directly from this project.
Why it matters
Potential benefit: If successful, this work could identify drug combinations that extend or restore the benefit of MAPK-targeted therapy across many melanoma subtypes.
How similar studies have performed: Previous RAF+MEK combinations helped many BRAFV600-mutant patients but resistance still occurs, and this broader proteogenomic and PDX atlas approach is relatively new and aims to address those gaps.
Where this research is happening
Los Angeles, United States
- University of California Los Angeles — Los Angeles, United States (Active)
Researchers
- Principal investigator: Lo, Roger S — University of California Los Angeles
- Study coordinator: Lo, Roger S
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.