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Targeting glutathione metabolism for tumor radiosensitization (Review)
Haonan Xu1, Meng Du2, Xiaowen Liang2
1School of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, P.R. China.
International Journal of Molecular Medicine
|June 19, 2026
Summary
Elevated glutathione (GSH) levels in tumors cause radioresistance by neutralizing cancer-killing ROS. Targeting GSH metabolism offers a strategy to enhance radiotherapy efficacy by increasing oxidative stress in cancer cells.
Area of Science:
- Oncology
- Radiotherapy
- Redox Biology
Background:
- Radiotherapy is a key cancer treatment, inducing tumor cell death via reactive oxygen species (ROS).
- Elevated glutathione (GSH) in tumors scavenges ROS, leading to radioresistance and reduced treatment effectiveness.
- Redox regulation is crucial in cancer, highlighting GSH metabolism as a therapeutic target.
Purpose of the Study:
- To review mechanisms of GSH metabolism in radioresistance.
- To survey novel therapeutic strategies targeting GSH for radiosensitization.
- To explore methods for intensifying oxidative stress in GSH-high tumors.
Main Methods:
- Literature review of studies on GSH metabolism and radiotherapy.
- Analysis of pharmacological and nanotechnology-based approaches to inhibit GSH synthesis or promote depletion.
- Evaluation of strategies to enhance oxidative stress in tumors with high GSH content.
Main Results:
- GSH metabolism significantly contributes to radioresistance by ROS scavenging.
- Inhibiting GSH synthesis or promoting its depletion can sensitize tumors to radiotherapy.
- Pharmacological agents and nanodelivery systems show promise in targeting GSH metabolism.
- These approaches aim to increase oxidative stress, improving radiotherapy outcomes.
Conclusions:
- Targeting GSH metabolism is a promising strategy to overcome radioresistance.
- Novel therapeutic approaches, including nanomedicine, can enhance radiotherapy by modulating GSH levels.
- Intensifying oxidative stress in tumors with high GSH content may improve radiotherapeutic outcomes.
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