Researchers have identified the Nrf2-HMOX1 pathway as a key mediator of cisplatin resistance in non-small cell lung cancer (NSCLC), unveiling a mechanism that cancer cells use to evade ferroptosis, a regulated iron-dependent cell death. By upregulating HMOX1 under Nrf2 transcriptional control, tumor cells degrade heme groups and modulate oxidative stress to suppress ferroptosis, maintaining survival despite chemotherapy. This discovery, based on advanced in vitro and in vivo NSCLC models, highlights potential points of therapeutic intervention to overcome drug insensitivity in one of the deadliest cancers worldwide.