NRF2, while cytoprotective, transcriptionally controls iron and heme genes (e.g., ferritin, heme oxygenase 1) and can dampen ferroptotic susceptibility; its sustained activation in glioblastoma multiforme aligns with hypoxic adaptation, HIF-1α/VEGF signaling, and reduced chemosensitivity, whereas NRF2 inhibition restores apoptosis and temozolomide responsiveness [6,8]. The gene discussed is HIF1A; the disease is glioblastoma.