Novel insight into the Warburg effect: Sweet temptation
Heng Zhang, Siyu Liu, Shengfeng Fu, Qihan Zhao, Yuheng Wang, Yin Yuan, Changhe Zhang
Abstract
Metabolic reprogramming is an important feature of tumors, and reprogramming of glucose metabolism was the earliest identified marker of metabolic alterations in tumors. The Warburg effect describes the propensity of tumor cells to preferentially metabolize glucose through glycolysis, even in the presence of oxygen, rather than relying on oxidative phosphorylation. This unique metabolic phenotype empowers cancer cells to proliferate and invade indefinitely, inducing metabolic adaptations that provide cancer cells with a survival advantage in hypoxic and nutrient-poor environments. Various mechanisms are able to promote the Warburg effect, and the adverse effects are complex and diverse. This review primarily examines the Warburg effect in tumor cells, and systematically investigates the influence of factors such as glycolytic enzymes, mitochondrial function, tumor microenvironment, and oncogenes on the Warburg effect. It comprehensively summarizes the underlying mechanisms of reactions and corresponding targeted drugs while discussing their potential applications in anticancer therapy. Elevated aerobic glycolysis activity represents a key characteristic of tumor cells, which can offer new insights for early diagnosis and treatment of cancer. Furthermore, in the context of recent research advancements, this review discusses how these insights may contribute to the development of novel therapeutic strategies. which is a difficult and meaningful challenge.