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Compounds activate key cancer enzyme to interfere with tumor formation
Date:8/27/2012

Scientists have known for decades that cancer cells use more glucose than healthy cells, feeding the growth of some types of tumors. Now, a team that includes researchers from the National Institutes of Health's new National Center for Advancing Translational Sciences (NCATS) has identified compounds that delay the formation of tumors in mice, by targeting a key enzyme that governs how cancer cells use glucose and its metabolites.

The study, published August 26 in the advance online publication of Nature Chemical Biology, was led by researchers from the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT), Cambridge. Researchers from the Structural Genomics Consortium at the University of Toronto and Harvard Medical School, Boston, also joined NCATS scientists to author the paper.

All cells use an enzyme called pyruvate kinase to derive energy from glucose. Recent studies have shown that cancer cells preferentially use one form of pyruvate kinase, called PKM2, which uses glucose to make additional cancer cells instead of energy. This altered metabolic state appears to be a fundamental aspect of many cancers, and reversing the process represents a new opportunity for cancer treatment.

In the study report, the researchers describe the identification of molecular compounds that activate PKM2, correct the way human cancer cells use glucose, and delay tumor development and decrease tumor size in mice. The results support PKM2 activation as a potential therapeutic strategy for cancer. However, the researchers emphasized there is much more work needed to understand the implications of their findings for humans, such as determining what types of tumors might be sensitive to PKM2 activation.

"The last several years have brought an avalanche of new discoveries that have begun to explain a phenomenon of altered cancer cell metabolism first described almost 90 years ago," said Chr
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Contact: Geoff Spencer
spencerg@mail.nih.gov
301-435-0888

Source:Eurekalert

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