Melanoma: how tumor stress responses and the surrounding cells help cancer grow and resist treatment
The integrated stress response and the microenvironment in melanoma progression
Researchers are trying to block a cell stress pathway (the Integrated Stress Response) to make melanoma cells less able to survive, spread, or resist treatment for people with melanoma.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Pennsylvania NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project ID | NIH-11262884 on NIH RePORTER |
What this research studies
From a patient's perspective, the team is looking at how melanoma cells and nearby support cells (fibroblasts, blood vessel cells, and fat cells) communicate under stress to help tumors survive and spread. They focus on a stress-response protein called ATF4 and will turn it off in specific cell types using genetically engineered mice and lab-grown 3-D tumor models. The researchers will also test drugs that disrupt the Integrated Stress Response to see whether tumors shrink, stop metastasizing, or become more sensitive to existing therapies. Results come from lab and animal experiments and analysis of human tumor samples to guide future clinical approaches.
Who could benefit from this research
Good fit: People with cutaneous melanoma—especially those with advanced, metastatic, or treatment-resistant tumors—would be the most relevant group for future clinical translation of these findings.
Not a fit: Patients with non-melanoma skin conditions, early-stage tumors already cured by surgery, or tumors that do not activate the ISR pathway are unlikely to benefit directly from this basic-science work.
Why it matters
Potential benefit: If successful, this work could point to new ways to stop melanoma from spreading and make existing targeted drugs and immunotherapies work better.
How similar studies have performed: Preclinical studies and preliminary data show that disrupting the Integrated Stress Response or ATF4 can reduce tumor growth and metastasis in lab and animal models, but clinical benefit in people has not yet been established.
Where this research is happening
Philadelphia, United States
- University of Pennsylvania — Philadelphia, United States (Active)
Researchers
- Principal investigator: Koumenis, Constantinos — University of Pennsylvania
- Study coordinator: Koumenis, Constantinos
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.