Targeting of VPS18 by the lysosomotropic agent RDN reverses TFE3-mediated drug resistance

Dear Editor, Multidrug resistance(MDR)is still a major challenge for successful cancer treatments.Numerous mechanisms that confer therapy-induced drug resistance have been extensively investi-gated to explore how to combat the MDR.In this regard,lysosomal sequestration has demonstrated to be a mechanism contributing to drug resistance via an"off-target"effect in which hydrophobic and weakly basic chemotherapeutic agents are trapped in lvsosomes,seauesterina them from their targets.1