LOX Blockade Disrupts TNBC Mitochondrial Function and Creates Targetable Dependency in Preclinical Models

The MUSC team used genetic knockdown and pharmacologic LOX inhibition in TNBC cell lines and patient-derived xenografts. They measured ATP levels, mitochondrial membrane potential, ROS accumulation, and activation of compensatory survival pathways via proteomics and functional assays. Blocking LOX reduced oxidative phosphorylation and induced reliance on an alternative kinase-mediated survival route that was then inhibited pharmacologically, producing additive growth arrest. This approach differs from prior extracellular LOX work focused on extracellular matrix remodeling. Observational data in public TNBC cohorts show elevated LOX expression correlates with chemoresistance, supporting mechanistic relevance. The strategy addresses rapid resistance emergence typical after initial chemotherapy response in this subtype lacking ER, PR, and HER2 targets.