Disulfiram:A novel repurposed drug for cancer therapyOACSTPCDMEDLINE

Cancer is a major global health issue.Effective therapeutic strategies can prolong patients'survival and reduce the costs of treatment.Drug repurposing,which identifies new therapeutic uses for approved drugs,is a promising approach with the advantages of reducing research costs,shortening development time,and increasing efficiency and safety.Disulfiram(DSF),a Food and Drug Administration(FDA)-approved drug used to treat chronic alcoholism,has a great potential as an anticancer drug by targeting diverse human malignancies.Several studies show the antitumor effects of DSF,particularly the combination of DSF and copper(DSF/Cu),on a wide range of cancers such as glioblastoma(GBM),breast cancer,liver cancer,pancreatic cancer,and melanoma.In this review,we summarize the antitumor mechanisms of DSF/Cu,including induction of intracellular reactive oxygen species(ROS)and various cell death signaling pathways,and inhibition of proteasome activity,as well as inhibition of nuclear factor-kappa B(NF-κB)signaling.Furthermore,we highlight the ability of DSF/Cu to target cancer stem cells(CSCs),which provides a new approach to prevent tumor recurrence and metastasis.Strikingly,DSF/Cu inhibits several molecular targets associated with drug resistance,and therefore it is becoming a novel option to increase the sensitivity of chemo-resistant and radio-resistant patients.Studies of DSF/Cu may shed light on its improved application to clinical tumor treatment.