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Targeting CDK4/6 reorganizes chromatin | Nature Cancer

Loss-of-function alterations in KEAP1 (or activating mutations in NRF2) allow tumor cells to hijack this pathway, leading to constitutive NRF2 activation, elevated antioxidant defenses (for example, GSH biosynthesis and detoxification enzymes) and enhanced tolerance to chemotherapy-induced oxidative injury 15

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This mechanical stress can cause the peptide to denature (unfold), which destroys its biological activity