A study by Wang et al. identified FBXL5 as a molecular driver of oxaliplatin resistance in iron‑rich colorectal cancers and showed that targeting FBXL5 sensitizes tumors to chemotherapy by triggering ferroptosis. The work combined mechanistic cell biology with preclinical models to propose FBXL5 as a druggable mediator of chemoresistance. The findings provide a translational route to combine FBXL5 inhibitors with existing platinum regimens in selected patients. For readers: ferroptosis is an iron‑dependent form of regulated cell death that can be therapeutically exploited to kill resistant tumor cells.