The Warburg Effect describes a phenomenon in which cancer cells voraciously consume glucose for energy—something scientists have long known, yet have had little success exploiting as a way to stunt tumor growth. Now researchers at Duke Cancer Institute have not only untangled an unusual wiring system that cancer cells use for carbohydrate metabolism, but also identified a natural compound that appears to selectively shut down this system in laboratory studies.
"The Warburg Effect has been known for decades, but the underlying mechanisms are not well understood," said Jason Locasale, assistant professor in the Department of Pharmacology & Cancer Biology at Duke and senior author of a study published Sept. 14 in the journal Cell Metabolism. "We started with the idea that if you understand how it works, you should be better able to control it, and we think we might have some insight on that, as well." Locasale and colleagues, including lead author Maria Liberti, studied cancer cells to determine how their metabolism changes so dramatically from that of normal cells, which use oxygen to break down sugar. Cancer cells, instead, use fermentation, which is less efficient and therefore uses more sugar. The researchers found particular points where carbohydrate metabolism is controlled differently in cancer cells undergoing the Warburg Effect, and they homed in on an enzyme, identified as GAPDH, that controls the rate at which glucose is processed in cancer cells. And while the Warburg Effect is strong in many cancers, it's absent or weaker in others. By measuring the GAPDH enzyme, the Duke team was able to develop a predictive model to measure how extensively cancer cells are under the influence of the Warburg Effect. Where the effect is strongest, the tumors could potentially be vulnerable to a therapy that targets the process.