Abstract
Metabolic transformation is a hallmark of cancer and a critical target for cancer therapy. Cancer metabolism and behaviour are regulated by cell-intrinsic factors as well as metabolite availability in the tumour microenvironment (TME). This metabolic niche within the TME is shaped by four tiers of regulation: (1) intrinsic tumour cell metabolism, (2) interactions between cancer cells and non-cancerous cells, (3) tumour location and heterogeneity and (4) whole-body metabolic homeostasis. Here, we define these modes of metabolic regulation and review how distinct cell types contribute to the metabolite composition of the TME. Finally, we connect these insights to understand how each of these tiers offers unique therapeutic potential to modulate the metabolic profile and function of all cells inhabiting the TME.
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Acknowledgements
We thank R. Boon, J. van Der Reest and J. Drijvers for valuable feedback on the manuscript. I.E. acknowledges funding from the European Molecular Biology Organization (EMBO) and the Cancer Research Institute (CRI). M.C.H. is supported by the Ludwig Center at Harvard, the Glenn Foundation for Medical Research and US National Institutes of Health grant RO1CA213062.
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Elia, I., Haigis, M.C. Metabolites and the tumour microenvironment: from cellular mechanisms to systemic metabolism. Nat Metab 3, 21–32 (2021). https://doi.org/10.1038/s42255-020-00317-z
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DOI: https://doi.org/10.1038/s42255-020-00317-z
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Plasma metabolites and risk of seven cancers: a two-sample Mendelian randomization study among European descendants
BMC Medicine (2024)
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PDGF-BB accelerates TSCC via fibroblast lactates limiting miR-26a-5p and boosting mitophagy
Cancer Cell International (2024)
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The roles and molecular mechanisms of non-coding RNA in cancer metabolic reprogramming
Cancer Cell International (2024)
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Longitudinal molecular profiling elucidates immunometabolism dynamics in breast cancer
Nature Communications (2024)
