Metabolic Targeting Strategies in Cancer Treatment

Cancer cells reprogramme their energy pathways to support rapid growth and survival under stress. Central to this reprogramming is the preferential use of glycolysis for ATP production, even in oxygenated conditions, alongside altered mitochondrial function and redox balance. Therapeutic strategies exploit these dependencies by inhibiting key glycolytic enzymes, blocking transporters responsible for lactate efflux, disrupting mitochondrial oxidative phosphorylation, or inducing stress responses that overwhelm tumour cell homeostasis. Combination approaches seek synthetic lethality by pairing metabolic inhibitors with agents such as kinase inhibitors or conventional chemotherapeutics. Emerging work also highlights the tumour microenvironment’s role, where acidity, hypoxia and immune suppression can be modulated through metabolic intervention. Together, these strategies offer the potential for selective tumour cell eradication, sensitisation to existing therapies and the development of precision medicine protocols tailored to metabolic phenotypes.

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Metabolic Targeting Strategies in Cancer Treatment publication trend

The graph below shows the total number of articles in metabolic targeting strategies in cancer treatment across all publications each year (not limited to Nature Index journals).

Technical terms

Warburg effect: The phenomenon by which cancer cells preferentially generate energy via glycolysis despite adequate oxygen supply.
Glycolysis: The enzymatic breakdown of glucose to pyruvate in the cytosol, producing ATP and NADH.
Oxidative phosphorylation: The mitochondrial process by which ATP is synthesised using a proton gradient across the inner membrane.
Monocarboxylate transporter (MCT1, MCT4): Membrane proteins that export lactate and protons from glycolytic cells to prevent intracellular acidification.
Integrated stress response (ISR): A cellular programme activated by metabolic or redox stress, leading to translational arrest and pro-apoptotic signalling.
Tumour microenvironment (TME): The network of stromal cells, immune infiltrates, vasculature, extracellular matrix and biochemical conditions surrounding a tumour.

References

1. Syrosingopine and UK5099 synergistically suppress non-small cell lung cancer by activating the integrated stress response. Cell Death & Disease (2024).
2. Clinical development of metabolic inhibitors for oncology. Journal of Clinical Investigation (2022).
3. Monocarboxylate transporter 1 blockade with AZD3965 inhibits lipid biosynthesis and increases tumour immune cell infiltration. British Journal of Cancer (2020).