Leveraging disulfiram to treat cancer: Mechanisms of action, delivery strategies, and treatment regimens

Disulfiram (DSF) has been used as an alcoholism drug for 70 years. Recently, it has attracted increasing attention owing to the distinguished anticancer activity, which can be further potentiated by the supplementation of Cu2+. Although encouraging anticancer results are obtained in lab, the clinical outcomes of oral DSF are not satisfactory, which urges an in-depth understanding of the underlying mechanisms, bottlenecks, and proposal of potential methods to address the dilemma. In this review, a critical summarization of various molecular biological anticancer mechanisms of DSF/Cu2+ is provided and the predicament of orally delivering DSF in clinical oncotherapy is explained by the metabolic barriers. We highlight the recent advances in the DSF/Cu2+ delivery strategies and the emerging treatment regimens for cancer treatment. Last but not the least, we summarize the clinical trials regarding DSF and make a prospect of DSF/Cu-based cancer therapy.

Automated summary

Disulfiram (DSF) has been used as an alcoholism drug for 70 years and has recently gained attention for its anticancer activity. However, the oral delivery of DSF in clinical settings has not yielded satisfactory outcomes, calling for a deeper understanding of its mechanisms and limitations. This review provides a critical summary of the molecular biological anticancer mechanisms of DSF/Cu2+ and explains the challenges of oral DSF delivery in clinical oncology. It also highlights recent advances in DSF/Cu2+ delivery strategies and emerging treatment regimens for cancer therapy.