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When we investigated the effects of DXd-based ADCs on SKBr3 cells, we found that the three drugs dampen Topoisomerase I levels and trigger senescence via activation of the p53/p21 pathway upon induction of DNA damage (Supplementary Fig

However, data concerning alterations of drug uptake by cells are scarce, so another mechanism (drug efflux from the resistant cell) is considered to be the main mechanism of the decreased drug accumulation in cells