An Updated Review on Disulfiram: Molecular Targets and Strategies for Cancer Treatment

: Repurposing already approved drugs as new anticancer agents is a promising strategy considering the advantages such as low costs, low risks and less time-consumption. Disulfiram (DSF), as the first drug for antialcoholism, was approved by the U.S. Food and Drug Administration (FDA) over 60 years ago. Increasing evidence indicates that DSF has great potential for the treatment of various human cancers. Several mechanisms and targets of DSF related to cancer therapy have been proposed, including the inhibition of ubiquitin-proteasome system (UPS), cancer cell stemness and cancer metastasis, and alteration of the intracellular reactive oxygen species (ROS). This article provides a brief review about the history of the use of DSF in humans and its molecular mechanisms and targets of anticancer therapy, describes DSF delivery strategies for cancer treatment, summarizes completed and ongoing cancer clinical trials involving DSF, and offers strategies to better use DSF in cancer therapies.