NADPH oxidase subunit 4 mediates cycling hypoxia-promoted radiation resistance in glioblastoma multiforme

► Nox4 is expressed predominantly in cycling hypoxic areas within the solid tumor. ► Tumor cycling hypoxia enhances Nox4 expression. ► Tumor cycling hypoxia increases reactive oxygen species levels via Nox4. ► Nox4 plays a critical role in cycling hypoxia-induced radioresistance. ► Nox4 blockage enhances the efficiency of radiotherapy in GBM xenografts.