Metabolic determinants of tumour initiation

This Review presents evidence that points to a critical role for metabolic pathways in influencing processes that support the early stages of tumour development, provides examples of the role of metabolic networks intrinsic to cancer cells in tumour progression and outlines how environmental factors can affect tumour incidence. Tumours exhibit notable metabolic alterations compared with their corresponding normal tissue counterparts. These metabolic alterations can support anabolic growth, enable survival in hostile environments and regulate gene expression programmes that promote malignant progression. Whether these metabolic changes are selected for during malignant transformation or can themselves be drivers of tumour initiation is unclear. However, intriguingly, many of the major bottlenecks for tumour initiation - control of cell fate, survival and proliferation - are all amenable to metabolic regulation. In this article, we review evidence demonstrating a critical role for metabolic pathways in processes that support the earliest stages of tumour development. We discuss how cell-intrinsic factors, such as the cell of origin or transforming oncogene, and cell-extrinsic factors, such as local nutrient availability, promote or restrain tumour initiation. Deeper insight into how metabolic pathways control tumour initiation will improve our ability to design metabolic interventions to limit tumour incidence.

Automated summary

This review emphasizes the important role of metabolic pathways in influencing the early stages of tumor development, highlighting the metabolic alterations present in cancer cells compared to normal cells. It discusses how these metabolic changes can support the growth and survival of tumors, as well as their potential impact on gene expression programs that promote malignant progression. The review also explores the factors, both intrinsic and extrinsic, that contribute to tumor initiation and underscores the significance of understanding how metabolic pathways control this process in the design of interventions to limit tumor incidence.