Lactate Metabolism in Cancer Biology

Cancer cells frequently adopt aerobic glycolysis, diverting pyruvate to lactate even in the presence of oxygen, a phenomenon known as the Warburg effect. This metabolic reprogramming fulfils biosynthetic and energetic demands while generating substantial amounts of lactate, which is exported via monocarboxylate transporters. Accumulation of lactate in the tumour microenvironment (TME) leads to acidification that promotes angiogenesis, extracellular matrix remodelling and immunosuppression. Lactate also acts as a signalling molecule, engaging dedicated G-protein-coupled receptors on cancer and stromal cells to modulate gene expression, cell motility and therapy resistance. Cross-talk between hypoxic tumour cores and better-perfused regions via lactate shuttling underpins intratumour heterogeneity, while interactions with immune cells skew macrophage polarization and inhibit cytotoxic lymphocytes. Enzymes such as lactate dehydrogenase isoforms and transporters that control lactate flux have emerged as critical regulators of metastatic potential and drug response. Together, these insights underscore lactate metabolism as a central nexus linking tumour bioenergetics, local acidity and paracrine signalling, and they point to therapeutic opportunities in targeting lactate production, transport or sensing to improve treatment outcomes.

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Lactate Metabolism in Cancer Biology publication trend

The graph below shows the total number of articles in lactate metabolism in cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

Warburg effect: The propensity of cancer cells to convert glucose to lactate under aerobic conditions, supporting biomass accumulation and rapid proliferation.

Monocarboxylate transporters (MCTs): Membrane proteins (notably MCT1 and MCT4) that facilitate bidirectional proton-linked transport of lactate and pyruvate across the cell membrane.

Lactate dehydrogenase (LDH): Enzyme family that interconverts pyruvate and lactate, with LDH-A favouring lactate production in glycolytic cells.

Tumour microenvironment (TME): The complex milieu surrounding tumour cells, comprising stromal elements, immune cells, extracellular matrix and soluble factors such as lactate.

GPR81 (HCAR1): A high-affinity G-protein-coupled receptor for lactate that transduces signals affecting cell survival, angiogenesis and immune modulation in cancer contexts.

References

1. Lactate oxidase/catalase-displaying nanoparticles efficiently consume lactate in the tumor microenvironment to effectively suppress tumor growth. Journal of Nanobiotechnology (2023).
2. Fusobacterium periodonticum BCT protein targeting glucose metabolism to promote the epithelial-mesenchymal transition of esophageal cancer cells by lactic acid. Journal of Translational Medicine (2024).
3. Lactate Contribution to the Tumor Microenvironment: Mechanisms, Effects on Immune Cells and Therapeutic Relevance. Frontiers in Immunology (2016).
4. Lactate in the Tumor Microenvironment: An Essential Molecule in Cancer Progression and Treatment. Cancers (2020).