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Funding The authors are grateful for the support of NIH grants R01NS039587, R01NS086423 and R01HD102071

388 Nrf2 inhibition Nrf2, frequently overexpressed in therapy-resistant cancers, represents a promising therapeutic target for ROS-mediated anticancer strategies, as demonstrated by Tamoxifen-resistant breast cancer cells that develop irradiation cross-resistance through Nrf2-driven antioxidant upregulation and a glycolytic shift, with Nrf2 inhibition restoring radiosensitivity in both cellular models and patient tumors (NCT00738777)