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Targeting cancer's sweet tooth
Date:10/21/2013

October 21, 2013, New York, NY 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 capabilityknown as the Warburg effectand 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."

Until recently, relatively little was known about the biochemical circuits that induce this vital metabolic shift in cancer cells. Earlier this year, however, Mischel and his colleagues published a study describing how an aberrant growth signal found in many glioblastomas is channeled to induce the Warburg effect. That signaling cascade, which involves the key proteins PI3 kinase (PI3K), Akt and mTORC1, culminates in the activation of a transcription factora controller of gene expressionnamed c-Myc. "In many cancer cells," says Mischel, "c-Myc seems to be a lever that links growth signaling pathways with the machinery that controls the uptake and use of nutrients."

In the current study, Mischel, who did the research in collaboration with Ludwig researchers Ke
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Contact: Rachel Steinhardt
rsteinhardt@licr.org
212-450-1582
Ludwig Institute for Cancer Research
Source:Eurekalert

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