# Absolute dynamic and relative static: the relationship of glycolysis and OXPHOS in cancer development

**Authors:** Xingting Bao, Boru Hou, Zhong Guo, Lei Song, Hailin Chen, Qian Zheng, Yongqing Zhao, Dandan Gao, Chenlong Fan, Xiaoyang Xiong, Chao Sun, Jin Zhao

PMC · DOI: 10.1038/s41420-026-02992-5 · Cell Death Discovery · 2026-03-05

## TL;DR

This paper reviews how cancer cells use both glycolysis and OXPHOS for energy, highlighting their metabolic flexibility and implications for cancer treatment.

## Contribution

The paper introduces a dialectical perspective on cancer metabolism, emphasizing dynamic shifts between glycolysis and OXPHOS.

## Key findings

- Tumor cells exhibit metabolic heterogeneity by relying on glycolysis or OXPHOS.
- Metabolic symbiosis occurs when glycolysis and OXPHOS operate simultaneously.
- Cancer cells dynamically switch between energy pathways influenced by the tumor environment and therapies.

## Abstract

For a significant period following the postulation of the Warburg effect, mitochondrial dysfunction and aerobic glycolysis were commonly accepted as the defining features of cancer. Currently, a deeper understanding of tumor metabolism has demonstrated that the energy phenotype of tumor cells is not solely glycolytic. Most cancer cells possess active mitochondria and still maintain the ability to undergo oxidative phosphorylation (OXPHOS) and utilize the tricarboxylic acid (TCA) cycle to support tumor growth. In this review, we examine the choice of energy supply pathways in tumor cells in both static and dynamic contexts. From a static standpoint, tumors contain cells that rely on glycolysis or OXPHOS for energy supply and demonstrate metabolic heterogeneity. Additionally, the simultaneous operation of glycolysis and OXPHOS establishes metabolic symbiosis. In contrast, cancer cells can also exhibit metabolic plasticity by dynamically shifting between glycolysis and OXPHOS to support tumor growth. This process is influenced by a variety of factors, such as the ever-changing tumor microenvironment, specific biological activities of tumor cells, and the effects of drug therapies. The relationship between glycolysis and OXPHOS suggests that in the process of cancer development, the stable state of energy metabolism is temporary, while the dynamic changes in energy metabolism are eternal, which is in line with the category of dialectical materialism and provides us with a new perspective for treating cancer.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Diseases:** cancer (MESH:D009369), mitochondrial dysfunction (MESH:D028361)
- **Chemicals:** TCA (MESH:D014233)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13039528/full.md

## References

6 references — full list in the complete paper: https://tomesphere.com/paper/PMC13039528/full.md

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Source: https://tomesphere.com/paper/PMC13039528