Glucose limitation protects cancer cells from apoptosis induced by pyrimidine restriction and replication inhibition

https://www.nature.com/articles/s42255-024-01166-w New insight into how cancer can beat chemo It’s known that chemotherapy doesn’t always work long-term for cancer patients, as tumor cells can expertly adapt to drugs. But less is known about how that happens. To find out, researchers scanned 3,000 cancer gene cells that are known to be involved with cell metabolism. They were particularly interested in how the level of nutrients in tumors can limit the effect of treatment. The study, published this morning in Nature, sheds light on how cells in glucose-limited tumors are already resistant to some drugs that aim to disrupt cancer metabolism. Some drugs work by preventing cancer cells from making molecules that are an essential part of RNA and DNA. Those molecules (called pyrimidines) are needed to make more food for the cell and to reproduce. Without them, cancer cells can quickly starve and die. But it turns out that in a low-glucose environment, a cancer cell will stretch out its food supplies, consuming what it already has on hand at a slower rate, leading to a slower death. In other experiments, researchers observed two proteins (BAX and BAK) that sit on the surface of the cancer cell mitochondria. When activated, those proteins disintegrate the powerhouse of the cell, leading to cell death. But low-glucose tumor microenvironments weren’t able to activate the proteins. It’s common for solid tumors to have limited glucose because the cells are eating it faster than they can import it, as STAT’s Angus Chen explained to me. The researchers hope the results could be used to develop more effective treatments in the future.