While our work supports a recently described mechanism of ferroptosis modulation by NRF2, it demonstrates, for the first time, the effect in glioblastoma cells: TMZ-resistant glioblastomas cells show higher vulnerability to ferroptosis induction due to high expression of NRF2 and its target ABCC1. Since high MRP1 expression is crucial to eliminating TMZ-resistant glioma cells through ferroptosis induction in vitro, exploiting collateral sensitivity by ferroptosis induction could be the Achilles’ heel to reverse drug resistance in glioblastoma. Here, ABCC1 is linked to central nervous system cancer.