ESR1 and breast cancer: For example, SIRT1 causes tamoxifen resistance in ER-α-positive BC cells through upregulation of multidrug resistance protein 2 by mediating deacetylation of FoxO1 protein.412 Subsequently, SIRT1 inhibition impairs nuclear FoxO1 and multidrug resistance protein 2 expression and augments the cytotoxic effect of paclitaxel and doxorubicin in tamoxifen-resistant BC cells.412 SIRT3 overexpression in BC cell line MTR-3 reduces the sensitivity of the resistant cells to tamoxifen.357,413 On the contrary, SIRT4 enhances the tamoxifen sensitivity of BC cells via inhibiting the STAT3 signaling pathway.