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Vascular disease

A new way to starve vascular endothelial cells

Nature Reviews Drug Discovery volume 13, pages 176–177 (2014)Cite this article

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Several anti-angiogenic drugs that block vascular endothelial growth factor (VEGF) or its receptors have been approved for the treatment of cancer and AMD. However, the effectiveness of these drugs can be limited and patients with cancer frequently develop resistance. So, Schoors and colleagues set out to investigate an alternative anti-angiogenic strategy, based on the knowledge that the endothelial cells that form new blood vessels generate approximately 85% of their ATP through glycolysis, rather than oxidative phosphorylation, which is the main route to producing ATP in many other cell types.

Previous attempts to reduce glycolysis therapeutically have mainly involved 2-deoxy-D-glucose (2-DG), a non-metabolizable glucose analogue that competes with glucose. These efforts have focused on the treatment of cancer, as cancer cells also generate a substantial proportion of their ATP through glycolysis, but initial trials showed a lack of efficacy and adverse effects including cardiac toxicity, which might be due in part to the almost complete blockade of glycolysis by 2-DG.

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References

  1. Schoors, S. et al. Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis. Cell Metab. 19, 37–48 (2014)

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  1. Megan Cully
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Cully, M. A new way to starve vascular endothelial cells. Nat Rev Drug Discov 13, 176–177 (2014). https://doi.org/10.1038/nrd4264

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