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REVIEW

Hexokinases and Glial Tumor Metabolism: A Bridge between Bioenergetics and Translational Oncology

Corina Ionela Tamas1,2, Flaviu Tamas1,2,*, Alina Roxana Cehan3, Adrian Balasa1,2
1 Department of Neurosurgery, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, Targu Mures, Romania
2 Department of Neurosurgery, Emergency Clinical County Hospital, Targu Mures, Romania
3 Doctoral School of Medicine and Pharmacy, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, Targu Mures, Romania
* Corresponding Author: Flaviu Tamas. Email: email

Oncology Research https://doi.org/10.32604/or.2026.079467

Received 21 January 2026; Accepted 06 May 2026; Published online 15 June 2026

Abstract

Hexokinases, particularly hexokinase 2, play a central role in the metabolic reprogramming of glioblastoma and other malignant glial tumors by promoting aerobic glycolysis and sustaining the Warburg phenotype. This review aims to summarize the current evidence regarding the molecular regulation, biological significance, and therapeutic implications of hexokinase isoenzymes in glial tumor metabolism. Recent studies consistently demonstrate that hexokinase 2 overexpression is associated with enhanced tumor proliferation, invasiveness, angiogenesis, resistance to chemotherapy and radiotherapy, and poor prognosis, especially in glioblastoma and high-grade gliomas. Multiple regulatory mechanisms, including microRNAs, long non-coding RNAs, the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, and hypoxia-inducible factor 1-alpha-mediated signaling, as well as mitochondrial interactions through the voltage-dependent anion channel, contribute to metabolic adaptation and tumor progression. In addition to its metabolic role, hexokinase 2 has emerged as an important mediator of the immunosuppressive tumor microenvironment and maintenance of the malignant phenotype. Overall, targeting hexokinase 2 and related glycolytic pathways represents a promising strategy for personalized metabolic therapy and may improve responsiveness to conventional oncologic treatments in patients with gliomas.

Keywords

Hexokinases; glial tumors; metabolism

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