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CANCER METABOLISM

New tricks for an old drug

Nature Chemical Biology volume 14, pages 990–991 (2018)Cite this article

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The prodrug dimethyloxalylglycine (DMOG) is a well-known tool compound used to study hypoxia. New findings reveal that DMOG also inhibits glutamine metabolism and can be exploited to selectively kill some cancer cells, highlighting important caveats when using DMOG for hypoxia studies.

Cancer cells have elevated biosynthetic and bioenergetic demands to support the production of cellular building blocks required for proliferation. Cancer cells must also meet these metabolic demands in the nutrient- and oxygen-poor tumor microenvironment4. The induction of oncogenes or loss of tumor suppressors promotes cancer survival by reprogramming metabolism. For example, rewired glutamine metabolism is a feature of many cancers. Glutamine is a preferred substrate because it can serve as a source of carbon to fuel mitochondrial anaplerosis through its conversion to αKG and as a nitrogen donor for nucleotide biosynthesis. On the basis of the dependence of some cancers on glutamine metabolism, the therapeutic utility of this metabolic vulnerability is an active area of preclinical and clinical research4.

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Fig. 1: DMOG metabolism and inhibitory activities.

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Authors and Affiliations

  1. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA

    Barbara S. Nelson, Daniel M. Kremer & Costas A. Lyssiotis

  2. Rogel Cancer Center and Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA

    Costas A. Lyssiotis

Authors
  1. Barbara S. Nelson
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  2. Daniel M. Kremer
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  3. Costas A. Lyssiotis
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Correspondence to Costas A. Lyssiotis.

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The authors declare no competing interests.

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Nelson, B.S., Kremer, D.M. & Lyssiotis, C.A. New tricks for an old drug. Nat Chem Biol 14, 990–991 (2018). https://doi.org/10.1038/s41589-018-0137-x

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