Targeting glutathione metabolism for tumor radiosensitization (Review)

Radiotherapy represents a cornerstone treatment modality in oncology and primarily mediates tumor cell death through the generation of reactive oxygen species (ROS). Nevertheless, elevated glutathione (GSH) levels within tumor cells can scavenge these ROS, thereby compromising the efficacy of radiotherapy and promoting the emergence of radioresistance. The contemporary understanding of redox regulation in cancer underscores the strategic relevance of targeting GSH metabolism in the context of radiotherapy. This review comprehensively describes the mechanisms through which GSH metabolism contributes to radioresistance and surveys novel therapeutic approaches aimed at inhibiting GSH synthesis or promoting its depletion to achieve radiosensitization. Both pharmacological compounds and nanotechnology‑enabled delivery systems have been investigated, with an emphasis on their ability to intensify oxidative stress in tumors characterized by high GSHcontent, thus potentially improving radiotherapeutic outcomes.