UCLA scientists have found how squamous cell skin cancer resists treatment by using fundamental metabolic mechanisms. Their study suggests that targeting multiple metabolic pathways simultaneously could improve cancer treatments.
This approach may help with skin cancer and other cancers with similar metabolic traits. UCLA professor William Lowry led the research, which was published in Science Advances.
In 2019, UCLA scientists, led by William Lowry, discovered that squamous cell skin cancer cells can adapt when glucose is unavailable by using glutamine for energy. This discovery challenges the old belief that cancer mainly relies on glucose.
Their research shows that targeting only one energy pathway is ineffective because tumors can switch to other nutrients. New experiments confirmed this, as blocking glutamine forced tumors to use different energy sources.
Galván described cancer cells as being like “whack-a-mole” because they quickly switch to another when one nutrient pathway is blocked. To counter this, the researchers used a “double hammer” method, blocking both glucose and glutamine pathways, which stopped the cancer from growing in mice.
Researchers found that cancer cells adapt by quickly moving proteins to the cell surface, allowing them to use different nutrients—not by changing their genes, as expected.
The research team is working to turn their genetic findings into drug treatments that target cancer’s metabolic processes. They aim to find the right combination of drugs to block both glucose and glutamine pathways, as seen in their genetic experiments.
They are also exploring a topical treatment, like a gel or lotion, to directly target skin cancer, which could be safer than oral treatments. This method might also help treat cancers that use similar metabolic pathways, like melanoma.
The researchers study how proteins and cell processes help cancer cells adapt to metabolic changes. Understanding how cancer cells detect and respond to stress could lead to new ways to stop them from switching energy sources rather than just blocking their nutrient pathways with drugs. The drugs tested are still experimental and haven’t been approved for human use yet.
Journal reference :
- Carlos Galvan,  Aimee A. Flores et al., Defining metabolic flexibility in hair follicle stem cell induced squamous cell carcinoma. Science Advances. DOI: 10.1126/sciadv.adn2806.
