The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart
This mechanistic study combines a mouse model with rodent and human cardiomyocyte platforms to characterize trametinib cardiotoxicity. Mice developed contractile dysfunction within three days and heart failure within two weeks. Trametinib impaired mitochondrial respiration and electron-transport activity, promoted release of mitochondrial danger signals including mtDNA, and activated innate immune pathways such as cGAS-STING. A phosphomimetic STAT3-S727 construct reversed the respiratory lesion in cell models.
Thai researchersNanthip Prathumsap