Why some cancers resist treatments that block cell recycling
Resistance mechanisms to autophagy-modulating therapies
This work will see if blocking cancer cell recycling (autophagy) together with targeting cholesterol-related enzymes helps people with advanced melanoma respond better to treatment.
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-11295393 on NIH RePORTER |
What this research studies
From a patient perspective, researchers at the University of Pennsylvania are studying how tumors escape therapies that block autophagy, the cell's recycling system. They found that these treatments can trigger changes in cancer cell membranes called lipid rafts by upregulating cholesterol and sphingolipid salvage pathways. The team is exploring whether adding a drug that targets the enzyme UGCG (an FDA-approved drug, eliglustat, exists for other uses) can block that escape route and make autophagy-blocking approaches work better. Experiments so far in animal models show promising synergy, and the goal is to translate those findings toward treatments for people with advanced melanoma.
Who could benefit from this research
Good fit: Ideal candidates would be people with advanced or treatment-resistant melanoma whose tumors are not responding to standard targeted therapies or immunotherapy.
Not a fit: People with early-stage melanoma, other cancer types that do not use these lipid pathways, or tumors lacking the specific molecular changes studied may not benefit.
Why it matters
Potential benefit: If successful, this approach could help some people with advanced melanoma who don't respond to current targeted or immune therapies to achieve better tumor responses.
How similar studies have performed: Early clinical trials combining autophagy inhibitors with other cancer therapies have shown encouraging response signals, and preclinical data support the idea that pairing autophagy inhibition with lipid-pathway targeting could be effective.
Where this research is happening
Philadelphia, United States
- University of Pennsylvania — Philadelphia, United States (Active)
Researchers
- Principal investigator: Amaravadi, Ravi K — University of Pennsylvania
- Study coordinator: Amaravadi, Ravi K
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.