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Clinical samples and model studies further validate the clinical significance of the ACSL4–LPCAT3 axis: in drug-resistant tumor tissues from patients with triple-negative breast cancer, ACSL4 expression levels were 2.8-fold higher than in sensitive tumors, and patients with high ACSL4 expression exhibited significantly enhanced responses to ferroptosis inducers combined with chemotherapy ( 2.1.3 Iron homeostasis imbalance Drug-resistant cancer cells, including cancer stem cells (CSCs), exhibit constitutive dysregulation of iron metabolism that prioritizes labile Fe² + accumulation—an essential catalyst for ferroptosis