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Rethinking our approach to cancer metabolism to deliver patient benefit

British Journal of Cancer volume 129, pages 406–415 (2023)Cite this article

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Abstract

Altered cellular metabolism is a major mechanism by which tumours support nutrient consumption associated with increased cellular proliferation. Selective dependency on specific metabolic pathways provides a therapeutic vulnerability that can be targeted in cancer therapy. Anti-metabolites have been used clinically since the 1940s and several agents targeting nucleotide metabolism are now well established as standard of care treatment in a range of indications. However, despite great progress in our understanding of the metabolic requirements of cancer and non-cancer cells within the tumour microenvironment, there has been limited clinical success for novel agents targeting pathways outside of nucleotide metabolism. We believe that there is significant therapeutic potential in targeting metabolic processes within cancer that is yet to be fully realised. However, current approaches to identify novel targets, test novel therapies and select patient populations most likely to benefit are sub-optimal. We highlight recent advances in technologies and understanding that will support the identification and validation of novel targets, re-evaluation of existing targets and design of optimal clinical positioning strategies to deliver patient benefit.

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Fig. 1: Key steps to clinical success in cancer metabolism.

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Acknowledgements

We would like to acknowledge all members of Cancer Research Horizons and the Cancer Research UK Beatson Institute who were involved in relevant discussions or gave suggestions based on draft versions of this review. We particularly want to thank Neil Jones, Nathan Breeds and David Sumpton.

Funding

This work was funded by Cancer Research UK award A23982 to ST.

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Authors and Affiliations

  1. The Cancer Research UK Beatson Institute, Glasgow, UK

    Saverio Tardito

  2. Institute of Cancer Sciences, University of Glasgow, Glasgow, UK

    Saverio Tardito

  3. Cancer Research Horizons, The Cancer Research UK Beatson Institute, Glasgow, UK

    Craig MacKay

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  1. Saverio Tardito
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  2. Craig MacKay
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ST drafted and revised the manuscript and approved the final version. CM conceived the review, drafted and revised the manuscript and approved the final version.

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Correspondence to Craig MacKay.

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ST is the inventor of PlasmaxTM medium.

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Tardito, S., MacKay, C. Rethinking our approach to cancer metabolism to deliver patient benefit. Br J Cancer 129, 406–415 (2023). https://doi.org/10.1038/s41416-023-02324-9

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