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Targeting cancer’s sweet tooth
Ludwig researchers have elucidated a key mechanism by which cancer cells change how they metabolize glucose to generate the energy and raw materials required to sustain runaway growth.
Published online in Cell Metabolism, the Ludwig Cancer Research study also reveals how the aggressive brain cancer glioblastoma harnesses the mechanism to resist targeted therapies that should disrupt this capability—known as the Warburg effect—and suggests how such resistance might be overcome. In detailing the molecular circuitry of the phenomenon, the researchers uncover several possible targets for new drugs that might disrupt cancer cell metabolism to destroy tumors.
"Cancer and other fast-growing cells extract energy from glucose using a process that ordinarily kicks in only when oxygen is in short supply," explains Ludwig scientist Paul Mischel, MD, who is based at the University of California, San Diego School of Medicine. "This allows them to thread the needle: they get the energy they need from glucose but also retain the carbon-based building blocks for molecules like lipids, proteins and DNA, which dividing cells need in large quantities."
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FIGURE 1 | Glucose metabolism in mammalian cells. From the following article: Why do cancers have high aerobic glycolysis? Robert A. Gatenby & Robert J. Gillies. Nature Reviews Cancer 4, 891-899 (November 2004) doi:10.1038/nrc1478