The combination of disulfiram and copper for cancer treatment

•Disulfiram, an anti-alcoholism drug, was found owing anti-tumor activity.•The combination of Disulfiram and copper greatly enhances its anti-tumor efficacy.•Disulfiram in combination with copper has been shown to reverse drug resistance in cancer through targeting ALDH, NF-κB pathway, MAPK pathway and so on. Disulfiram (DSF) is a thiuram derivative that was developed to treat alcoholism but was also found to have antitumor activity. Copper (Cu), as a trace metal, has important roles in the body. Numerous studies have shown that the combination of DSF and copper (DSF/Cu) greatly enhances its antitumor efficacy. Given that the efficacy of DSF is well established and its safety profile is understood, repurposing DSF as a new anticancer drug is a promising strategy. Here, we summarize the pharmacological effects of DSF and the role of Cu in cancer, and focus on the antitumor effect of DSF/Cu, especially the mechanisms involved in enhancing drug sensibility by targeting specific molecules. We also provide rational strategies for using DSF as a cancer therapy.