A new study reveals that the Nrf2 transcription factor and its downstream target HMOX1 play central roles in mediating cisplatin resistance in non-small cell lung cancer (NSCLC). This resistance operates via suppression of ferroptosis, a regulated cell death modality, thus enabling tumor survival despite chemotherapy. Using rigorous molecular models, the work underscores potential therapeutic targeting of this pathway to restore cisplatin sensitivity, marking a significant advancement in tackling drug resistance in NSCLC.