On page 93, Yuneva et al. provide bittersweet news for efforts to turn cancer cells' big appetite against them. Contrary to previous work, the study shows that a sugar shortage snuffs out normal cells as well as cancer cells. But the results bolster another nutritional target: the amino acid glutamine.
The idea that cancer cells hunger for glucose is more than 50 years old. In the 1990s, researchers showed that glucose depletion kills rodent cells that carry an overactive form of the cancer-promoting gene MYC. Nontransformed cells survived.
Tumors also need plenty of glutamine, and two drugs that disrupt metabolism of the amino acid reached clinical trials but have since proved toxic. Some scientists question whether scarcity of either nutrient is lethal to human tumors: cancer cells synthesize their own glutamine, and some tumors switch to alternative food sources if glucose runs out. Yuneva et al. wanted to nail down whether the nutrients are essential for cells with overactive MYC.
To their surprise, the researchers found that, unlike rodent cells, human cells were killed by glucose deprivation whether or not extra MYC was present. By contrast, shutting off the glutamine supply had a stronger effect on MYC-overproducing cells. The results suggest that glutamine deprivation as a cancer treatment—which researchers have abandoned—deserves a second look. The findings don't show that glucose deprivation is a bust, the authors caution. Instead, they say, scientists need to carefully compare the intricacies of metabolism in normal and cancer cells before they can predict whether such treatments will work.