Potential applications of PFKFB in cancer treatment strategies

The glycolytic pathway has significant metabolic significance in rapidly proliferating cells, such as cancer cells. Phosphofructokinase-1 (PFK-1) is a key enzyme in glycolysis, regulated by conformational changes in various cytoplasmic substances, particularly fructose-2,6-diphosphate (F-2,6-BP). The level of F-2,6-BP is closely related to the activity of the bifunctional enzyme PFK-2/FBPase-2 (PFKFB), which regulates the synthesis and degradation of F-2,6-BP. The known PFKFB isoenzymes include PFKFB1, PFKFB2, PFKFB3, and PFKFB4, and their level changes in disease states have been widely studied. This review focuses on the upregulation of PFKFB3 and PFKFB4 expression in cancer tissues and their roles in carcinogenesis. It summarizes the latest research on PFKFB2, PFKFB3, and PFKFB4 in tumor progression, metastasis, angiogenesis, and autophagy, aiming to provide literature references for future glycolysis research. In addition, this review also explores the development of novel drugs targeting these isoenzymes and discusses the potential application of PFKFB inhibitors in combination therapy, which may be a key strategy for future cancer treatment.