Metabolic Modification of Cancer Cell Dynamics

Cancer cells rewire their energy metabolism to support proliferation, survival and invasiveness. A hallmark of this process is the preferential use of aerobic glycolysis rather than mitochondrial oxidative phosphorylation, known as the Warburg effect. Such metabolic reprogramming influences cell signalling, redox balance and the epigenetic landscape, enabling dynamic adaptation to microenvironmental stresses. Tumour heterogeneity at the metabolic level gives rise to subpopulations with distinct glycolytic or oxidative profiles, which may interconvert in response to therapy or nutrient availability. Cross-talk between pathways, including autophagy and senescence programmes, further modulates stemness and treatment resistance. Targeting key nodes in metabolic networks—such as pyruvate dehydrogenase kinase, glycolytic enzymes or mitochondrial regulators—offers opportunities to disrupt cancer cell fitness and overcome resistance. Recent advances highlight both small molecules and natural compounds that shift the balance between glycolysis and oxidative phosphorylation, enhancing reactive oxygen species accumulation, restoring apoptotic signalling and sensitising tumours to chemotherapy. A deeper understanding of metabolic plasticity and the interplay between cellular subpopulations promises to inform more precise and effective therapeutic strategies.

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Metabolic Modification of Cancer Cell Dynamics publication trend

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

Technical terms

Aerobic glycolysis (Warburg effect): The preference of cancer cells to metabolise glucose to lactate despite oxygen availability, supporting rapid ATP production and biosynthesis.

Oxidative phosphorylation: Mitochondrial process that uses oxygen to generate ATP through electron transport and the Krebs cycle.

Autophagy: A conserved cellular degradation pathway that recycles organelles and macromolecules under stress conditions.

Senescence: A state of permanent cell-cycle arrest accompanied by characteristic secretory and metabolic changes.

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen that can modulate signalling or induce oxidative damage.

Pyruvate dehydrogenase kinase (PDK): A mitochondrial enzyme that inhibits the conversion of pyruvate to acetyl-CoA, thus regulating the balance between glycolysis and oxidative phosphorylation.

References

1. Compensatory cross-talk between autophagy and glycolysis regulates senescence and stemness in heterogeneous glioblastoma tumor subpopulations. Acta Neuropathologica Communications (2023).
2. Ginsenoside Rh2 shifts tumor metabolism from aerobic glycolysis to oxidative phosphorylation through regulating the HIF1-α/PDK4 axis in non-small cell lung cancer. Molecular Medicine (2024).
3. Metabolic reprogramming induced by DCA enhances cisplatin sensitivity through increasing mitochondrial oxidative stress in cholangiocarcinoma. Frontiers in Pharmacology (2023).