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RAC2 drives hypoxia-mediated radiation resistance in nasopharyngeal carcinoma
Huaiyuan Chen1, Haojiong Zhang1, Xingyu Liu1
1Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, 201321, China; Shanghai Key Laboratory of Radiation Oncology (20dz2261000), Shanghai, 201321, China; Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, 201321, China.
None:
Nasopharyngeal carcinoma (NPC) exhibits unique radiosensitivity, yet radioresistance remains a major therapeutic challenge. This study investigates the role of RAC2 in hypoxia-induced radioresistance through reactive oxygen species (ROS) regulation. Radiation effectiveness was demonstrated through dose-dependent DNA damage, proliferation inhibition, and ROS elevation in NPC cells, while hypoxic conditions attenuated these effects. Mechanistically, RAC2 was identified as a crucial mediator of hypoxia-induced radioresistance by modulating NADPH oxidase-derived ROS production. The findings reveal that RAC2 drives hypoxia-associated radioresistance in NPC by amplifying ROS production, suggesting its potential as a therapeutic target for radiosensitization. This research provides new insights into overcoming hypoxia-mediated radioresistance in NPC treatment.
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