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Liver

Liver cancer metabolism: a hexokinase from the stars

Nature Metabolism volume 4, pages 1225–1226 (2022)Cite this article

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Hepatocellular carcinoma (HCC) is the 4th leading cause of cancer mortality. Modulation of tumour metabolism may represent a novel therapeutic strategy. Hexokinase 1, secreted into extracellular vesicles by activated hepatic stellate cells, is shown to be taken up by tumour cells, where it accelerates glycolysis and HCC growth.

Hepatocellular carcinoma (HCC) kills nearly 800,000 people per year world-wide and is expected to further increase due to surging rates of obesity and non-alcoholic fatty liver disease1,2. Despite a low degree of actionable mutations, there has been substantial progress in the therapy of HCC, with the most effective therapies, such as the combination of Atezolizumab plus Bevacizumab, targeting the tumour microenvironment (TME)1,3. In contrast, therapeutic targets within tumour cells are not clearly established, since clinically employed tyrosine kinase inhibitors may not only affect tumour cells but also the fibrotic TME. With metabolic reprogramming playing a major role in HCC growth and often being conserved between tumours with different mutational profiles4, metabolic pathways provide an attractive option for tumour cell-targeted therapies and may synergize with existing TME-targeted therapies.

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Fig. 1: HK1 transfer from HSCs to HCC boost glycolysis and tumour growth.

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Acknowledgements

RFS is supported by NIH grants 5R01CA262424-02 and 1R01CA262424-01.

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  1. Department of Medicine, Columbia University, New York, NY, USA

    Aveline Filliol & Robert F. Schwabe

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  1. Aveline Filliol
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  2. Robert F. Schwabe
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Correspondence to Robert F. Schwabe.

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Filliol, A., Schwabe, R.F. Liver cancer metabolism: a hexokinase from the stars. Nat Metab 4, 1225–1226 (2022). https://doi.org/10.1038/s42255-022-00659-w

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