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Circadian disruption induces the activation of the constitutive androstane receptor (CAR) through mechanisms that promote cholestasis, peripheral clock disruption, and sympathetic dysfunction

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Even after drug withdrawal, treatment-induced chromatin landscape alterations (e.g., reduced H3K27me3 at key gene promoters) may persist, enabling cells to more rapidly initiate resistance mechanisms upon re-exposure to the same treatment [162, 163]