Abstract
Cancer cells rewire their metabolism to survive during cancer progression. In this context, tumour metabolic heterogeneity arises and develops in response to diverse environmental factors. This metabolic heterogeneity contributes to cancer aggressiveness and impacts therapeutic opportunities. In recent years, technical advances allowed direct characterisation of metabolic heterogeneity in tumours. In addition to the metabolic heterogeneity observed in primary tumours, metabolic heterogeneity temporally evolves along with tumour progression. In this Review, we summarize the mechanisms of environment-induced metabolic heterogeneity. In addition, we discuss how cancer metabolism and the key metabolites and enzymes temporally and functionally evolve during the metastatic cascade and treatment.
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Acknowledgements
We thank Q. Wu (KU Leuven) for her help with article collection and organisation and P. Altea-Manzano (VIB-KU Leuven) for comments and suggestions. X.-Z.L. is supported by an EMBO Postdoctoral Fellowship (ALTF 401-2022) and the Gilead Sciences Research Scholars Program in Solid Tumors. K.L. acknowledges funding from the Austrian Science Fund (P33508). S.-M.F. acknowledges funding from FWO and iBOF (INTERCEPt) Projects, the Beug Foundation, Fonds Baillet Latour, KU Leuven, Francqui Stichting, Foundation ARC and Stichting tegen Kanker.
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M.D. and X.-Z.L. elaborated on the concepts and wrote the draft under S.-M.F.’s supervision. M.D., X.-Z.L. and S.-M.F. reviewed and edited the manuscript; figures were prepared by M.D., X.-Z.L. and K.L. All authors contributed to the article and approved the submitted version.
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S.-M.F. has received funding from Gilead, Auron Therapeutics, Black Belt Therapeutics and Alesta Therapeutics, has consulted for Fund+ and is on the advisory board of Alesta Therapeutics. All other authors declare no competing interests.
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Demicco, M., Liu, XZ., Leithner, K. et al. Metabolic heterogeneity in cancer. Nat Metab 6, 18–38 (2024). https://doi.org/10.1038/s42255-023-00963-z
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DOI: https://doi.org/10.1038/s42255-023-00963-z
