Glucose Metabolism Modulation as a Strategy to Enhance Cancer Radiotherapy

A systematic literature review of the PubMed database, filtering for publication dates up to and including October 2025, was conducted to identify relevant studies on glucose metabolism and radiotherapy. Radioresistance poses a major therapeutic challenge, in which tumor-associated glucose metabolic reprogramming, characterized by the Warburg effect, supports cellular energy requirements and contributes to radioresistance by facilitating DNA repair and promoting survival pathways. Targeting pivotal glycolytic enzymes, such as hexokinase (HK) and pyruvate kinase M2 (PKM2), and integrating radiotherapy with metabolic modulators have been shown to improve radiosensitivity. Special emphasis is placed on how these interventions remodel the tumor microenvironment and modulate antitumor immunity-emerging factors that influence therapeutic efficacy. This review highlights mechanistic insights and potential therapeutic targets for the development of effective radiosensitization strategies.