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

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.