Hexokinase 2 promotes tumor development and progression

Cancer remains a leading cause of morbidity and mortality worldwide, and the abnormal activation of glycolysis is a hallmark that enables tumor cells to adapt and sustain rapid proliferation. Beyond providing energy and biosynthetic precursors, glycolysis also supports tumor cell survival, invasion, and metastasis through multiple mechanisms. Hexokinase is a key rate-limiting enzyme in glycolysis, catalyzing the phosphorylation of glucose to glucose-6-phosphate. Among its isoforms, hexokinase 2 (HK2) exhibits particularly high enzymatic activity and substrate specificity, and it plays a central role in tumor metabolic reprogramming. Recent studies have shown that HK2 is markedly upregulated in many cancer types, where it promotes tumor initiation and progression by suppressing apoptosis and enhancing proliferation and metastasis. This review summarizes current evidence on the role of HK2 in tumor development and discusses emerging therapeutic strategies targeting HK2. By clarifying the link between HK2 and cancer, we aim to provide new insights and potential clinical applications for metabolism-based therapies.