Exploring how metabolism comes into play with radiations: a review

Ionizing radiation consists in the emission of photons such as X- and $\gamma$-rays or particles like carbon ions or $\alpha$-particles. Glucose metabolism, encompassing glycolysis and oxidative phosphorylation, plays a central role in cellular energy production. Emerging evidence reveals a complex and reciprocal relationship between ionizing radiation and glucose metabolism, with significant implications for radiotherapy outcomes. This review provides a comprehensive overview of the molecular and cellular interactions between these two processes, highlighting both historical findings and recent advances.

Irradiation induces transient increases in glycolytic enzyme activity and temporary suppression of mitochondrial respiration, suggesting a coordinated metabolic response. Reactive oxygen species (ROS) and HIF-1$\alpha$ appear as central regulators of this response, though their dynamics remain a topic of ongoing investigation. Importantly, a high glycolytic phenotype is consistently associated with increased radioresistance and poor clinical prognosis. Furthermore, glucose metabolism intersects with other modulators of radiosensitivity, including cancer stem cells and cell-cycle regulation. By synthesizing key biological insights, this review lays a foundation for future in silico modeling efforts aimed at understanding and potentially overcoming treatment resistance through metabolic targeting.