Triptolide suppresses IDH1-mutated malignancy via Nrf2-driven glutathione metabolism

Significance IDH1 mutation is a common genetic abnormality in human malignancies, whereas selective therapeutics for IDH1-mutated malignancies remain unavailable. Our present study reveals that IDH1-mutated cancer cells exhibit addiction to Nrf2-governed antioxidative pathways. Blockade of Nrf2 transcriptional activity achieved synergistic lethality with a neomorphic IDH1 mutation. We also showed that triptolide serves as a potent Nrf2...