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Cancer metabolism

When more is less

Nature volume 489, pages 511–512 (2012)Cite this article

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A tightly regulated enzyme balances energy production and the synthesis of macromolecules from glucose in cancer cells. Upsetting this balance by stimulating the enzyme's activity can suppress tumour growth in mice.

The development of cancer is associated with a suite of metabolic changes that support the energetic and biosynthetic requirements of tumour-cell proliferation. Many of these changes are stimulated by the same genetic mutations that drive tumorigenesis, suggesting that normalizing the tumour cells' metabolism by pharmacological means could suppress cancer progression. An enhancement of glycolysis, a cellular pathway that produces both energy and precursors of macromolecules, is a classic metabolic hallmark of cancer, making the glycolytic pathway an attractive target in which to test this hypothesis. Writing in Nature Chemical Biology, Anastasiou et al.1 show that targeting a form of the enzyme pyruvate kinase that is commonly found in tumour cells can redistribute the fate of glucose-derived metabolites away from biosynthetic pathways, and suppress tumour growth in mice.

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Figure 1: A metabolic bottleneck.

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Authors and Affiliations

  1. Lei Jiang and Ralph J. DeBerardinis are at the Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8502, USA.,

    Lei Jiang & Ralph J. DeBerardinis

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  1. Lei Jiang
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  2. Ralph J. DeBerardinis
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Correspondence to Lei Jiang.

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Competing interests

L.J. receives salary support from Janssen Pharmaceutica NV, Beerse, Belgium. R.J.D. is a consultant for Agios Pharmaceuticals, Cambridge, Massachusetts, and is on the scientific advisory board of Peloton Therapeutics, Dallas, Texas.

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Jiang, L., DeBerardinis, R. When more is less. Nature 489, 511–512 (2012). https://doi.org/10.1038/489511a

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