Cancer cells have big appetites and need certain nutrients to survive. Scientists have tried to stop cancer by cutting off these nutrients, but cancer cells often find other ways to get what they need by changing their metabolism.
CSHL Assistant Professor Michael Lukey has found a way to block cancer cells from getting an essential nutrient and their backup supply. This method killed cancer cells and reduced tumors in lab tests with breast cancer cells, patient tissue models, and mice. Aggressive cancer cells rely heavily on an amino acid called glutamine for energy and growth.
Earlier research showed that cutting off glutamine or stopping its conversion into other molecules can halt cancer cell growth in the lab. However, breast cancer patients didn’t see benefits from this approach in recent clinical trials, suggesting cancer cells can adapt without glutamine.
Lukey and postdoc Yijian Qiu observed the same in their lab. They found that breast cancer cells can switch on a pathway to produce alpha-ketoglutarate, a key metabolite usually made from glutamine, to keep growing.
This made Lukey’s team wonder if they could use this adaptation against cancer cells by blocking glutamine metabolism and the adaptive pathway simultaneously.
The approach worked, killing breast cancer cells in lab tests and treating tumors in mice. Tumors stopped growing and even shrank, while the mice stayed healthy.
Lukey’s team is further investigating inhibitors of both metabolic pathways. These pathways might be crucial for breast cancer spreading to hard-to-treat areas, like the brain. Lukey notes there are currently no effective treatments for brain metastases.
He hopes this combination therapy could boost the effectiveness of glutamine metabolism inhibitors in clinics, leading to new treatments that target cancer’s metabolic needs.
Journal reference :
- Qiu, Y., Stamatatos, O.T., Hu, Q. et al. The unique catalytic properties of PSAT1 mediate metabolic adaptation to glutamine blockade. Nature Metabolism. DOI: 10.1038/s42255-024-01104-w.