Blocking the protein S6K2 to fight drug-resistant NRAS-mutant melanoma
Targeting S6K2 to Overcome Drug Resistance in NRAS-mutant Melanoma
This project looks at whether blocking a protein called S6K2 can kill NRAS-mutant melanoma cells that resist current treatments.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Wistar Institute NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project ID | NIH-11159731 on NIH RePORTER |
What this research studies
If you have NRAS-mutant melanoma that doesn’t respond to standard drugs, the researchers aim to see if turning off S6K2 causes those cancer cells to die. They will use patient-derived melanoma cells and laboratory models that are resistant to MAPK pathway inhibitors, apply gene-editing (CRISPR) and selective blockers, and measure changes in metabolism and oxidative stress. The team will track whether S6K2 blockade triggers lipid peroxidation and tumor cell death in these models. The goal is to reveal a druggable weakness that could lead to new treatment options for patients with resistant NRAS-mutant melanoma.
Who could benefit from this research
Good fit: Patients whose melanoma tumors have NRAS mutations, particularly those whose disease progressed on approved targeted drugs or immunotherapy, would be the most relevant group.
Not a fit: Patients without NRAS-mutant melanoma or those who are doing well on existing approved treatments are unlikely to benefit from this specific approach.
Why it matters
Potential benefit: If successful, this work could point to a new targeted therapy that kills drug-resistant NRAS-mutant melanoma cells and improve outcomes for patients with few options.
How similar studies have performed: Previous preclinical studies showed S6 kinase activity supports resistance in BRAF-mutant melanoma, but selectively targeting the S6K2 isoform in NRAS-mutant melanoma is a newer and less-tested idea.
Where this research is happening
Philadelphia, United States
- Wistar Institute — Philadelphia, United States (Active)
Researchers
- Principal investigator: Villanueva, Jessie — Wistar Institute
- Study coordinator: Villanueva, Jessie
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.