NFE2L2 and cancer: NRF2 is a crucial transcription factor involved in cellular defense against oxidative and electrophilic stress.204 NRF2 acts as a suppressor of tumor initiation in the early stages of cancer.205–207 However, once oncogenic driver mutations occur, the high expression status of NRF2 in cancer cells may promote tumor progression and therapeutic resistance,208,209 partly through its ability to defend against ferroptosis.