Function (biology)

Metabolite

Cell biology

Cell metabolism

Biology

Metabolism

Cancer research

Biochemistry

Metabolic pathway

Genetics

Homeostasis

Niche

Bioinformatics

Tumor microenvironment

Tumor cells

Cell

Cancer

Metabolomics

Cancer cell

Cellular metabolism

Nature Metabolism

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.

Metabolites and the tumour microenvironment: from cellular mechanisms to systemic metabolism