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Cancer

A metabolic metamorphosis

Nature volume 496, pages 38–40 (2013)Cite this article

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Mutations in the enzyme isocitrate dehydrogenase lead to the accumulation of a metabolite that seems to promote cancer by influencing the epigenetic status of cells. But the effects are reversible, hinting at therapeutic targets.

The discovery of cancer-associated mutations in metabolic enzymes has fuelled the idea that altered cellular metabolism may be involved in the development of cancer. For example, mutations in isocitrate dehydrogenases 1 and 2 are commonly detected in brain tumours and leukaemia. These mutations cause the enzymes to produce the (R)-enantiomer of a metabolite called 2-hydroxyglutarate, which can accumulate in tissues1,2. Writing in Science, Losman et al.3 now show that the presence of this metabolite alone can promote cancer-like properties in cells. Notably, they also demonstrate that its cancer-promoting effects are reversible, suggesting that therapies targeting isocitrate-dehydrogenase mutants might improve patient prognoses.

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Figure 1: An oncogenic metabolite.

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Authors and Affiliations

  1. Abigail S. Krall and Heather R. Christofk are in the Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California 90095, USA.,

    Abigail S. Krall & Heather R. Christofk

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  1. Abigail S. Krall
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  2. Heather R. Christofk
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Corresponding authors

Correspondence to Abigail S. Krall or Heather R. Christofk.

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Competing interests

H.R.C owns equity in Agios, a biotechnology company developing IDH inhibitors.

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Krall, A., Christofk, H. A metabolic metamorphosis. Nature 496, 38–40 (2013). https://doi.org/10.1038/496038a

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