Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer

Minru Liao; Dahong Yao; Lifeng Wu; Chaodan Luo; Zhiwen Wang; Jin Zhang; Bo Liu

doi:10.1016/j.apsb.2023.12.003

Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer

Acta Pharm Sin B. 2024 Mar;14(3):953-1008. doi: 10.1016/j.apsb.2023.12.003. Epub 2023 Dec 16.

Authors

Minru Liao¹, Dahong Yao², Lifeng Wu¹, Chaodan Luo³, Zhiwen Wang^{1

2

4}, Jin Zhang⁴, Bo Liu¹

Affiliations

¹ Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
² School of Pharmaceutical Sciences, Shenzhen Technology University, Shenzhen 518118, China.
³ Department of Psychology, University of Southern California, Los Angeles, CA 90089, USA.
⁴ School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China.

Abstract

Cancer reprogramming is an important facilitator of cancer development and survival, with tumor cells exhibiting a preference for aerobic glycolysis beyond oxidative phosphorylation, even under sufficient oxygen supply condition. This metabolic alteration, known as the Warburg effect, serves as a significant indicator of malignant tumor transformation. The Warburg effect primarily impacts cancer occurrence by influencing the aerobic glycolysis pathway in cancer cells. Key enzymes involved in this process include glucose transporters (GLUTs), HKs, PFKs, LDHs, and PKM2. Moreover, the expression of transcriptional regulatory factors and proteins, such as FOXM1, p53, NF-κB, HIF1α, and c-Myc, can also influence cancer progression. Furthermore, lncRNAs, miRNAs, and circular RNAs play a vital role in directly regulating the Warburg effect. Additionally, gene mutations, tumor microenvironment remodeling, and immune system interactions are closely associated with the Warburg effect. Notably, the development of drugs targeting the Warburg effect has exhibited promising potential in tumor treatment. This comprehensive review presents novel directions and approaches for the early diagnosis and treatment of cancer patients by conducting in-depth research and summarizing the bright prospects of targeting the Warburg effect in cancer.

Keywords: Cancer; Drug resistance; LncRNAs; Regulatory factor; Small-molecule drug; Traditional Chinese medicine; Warburg effect; miRNAs.

Publication types

Review