Cancer Metabolism

Defining a metabolic landscape of tumours: genome meets metabolism

Abstract

Cancer is a complex disease of multiple alterations occuring at the epigenomic, genomic, transcriptomic, proteomic and/or metabolic levels. The contribution of genetic mutations in cancer initiation, progression and evolution is well understood. However, although metabolic changes in cancer have long been acknowledged and considered a plausible therapeutic target, the crosstalk between genetic and metabolic alterations throughout cancer types is not clearly defined. In this review, we summarise the present understanding of the interactions between genetic drivers of cellular transformation and cancer-associated metabolic changes, and how these interactions contribute to metabolic heterogeneity of tumours. We discuss the essential question of whether changes in metabolism are a cause or a consequence in the formation of cancer. We highlight two modes of how metabolism contributes to tumour formation. One is when metabolic reprogramming occurs downstream of oncogenic mutations in signalling pathways and supports tumorigenesis. The other is where metabolic reprogramming initiates transformation being either downstream of mutations in oncometabolite genes or induced by chronic wounding, inflammation, oxygen stress or metabolic diseases. Finally, we focus on the factors that can contribute to metabolic heterogeneity in tumours, including genetic heterogeneity, immunomodulatory factors and tissue architecture. We believe that an in-depth understanding of cancer metabolic reprogramming, and the role of metabolic dysregulation in tumour initiation and progression, can help identify cellular vulnerabilities that can be exploited for therapeutic use.

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Acknowledgements

We would like to thank all Yuneva lab members for discussion and comments on this review.

Author information

M.Y., C.S.N., S.V.V. and N.P. conceived the idea and wrote the review. Data analysis for Table 1 was done by C.S.N. and discussed with M.Y. Figures were made by C.S.N. with input from M.Y.

Correspondence to Mariia Yuneva.

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M.Y., C.S.N., S.V.V. and N.P. are supported by the Francis Crick Institute that receives its core funding from Cancer Research UK (FC001223), the UK Medical Research Council (FC001223) and the Wellcome Trust (FC001223), and by the CRUK Grand Challenge Award 2015 C57633/A25043. In addition, N.P. is affiliated with NIHR UCLH/UCL Biomedical Research Centre and UCL Cancer Institute.

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The data used for generating Table 1 are obtained from published studies in open-access journals and are freely available online as supplementary files of the respective articles.

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Seth Nanda, C., Venkateswaran, S.V., Patani, N. et al. Defining a metabolic landscape of tumours: genome meets metabolism. Br J Cancer 122, 136–149 (2020). https://doi.org/10.1038/s41416-019-0663-7

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