Advanced Science
Targeting the PHB2–ACSL3 Lipid‐Remodeling Axis Overcomes Cisplatin Resistance by Restoring Ferroptosis in Gastric Cancer
ABSTRACT Platinum‐based chemotherapy resistance remains a major obstacle in gastric cancer (GC) treatment. Through integrated transcriptomic profiling of cisplatin‐resistant xenografts and pharmacogenomic interrogation of the NCI‐60 dataset, we identified Prohibitin‐2 (PHB2) as a previously unrecognized determinant of chemoresistance. PHB2 was consistently upregulated in resistant tumors and associated with poor clinical outcomes. Mechanistically, PHB2 binds the lipid‐metabolic enzyme ACSL3 through a defined AMP‐bi …