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

Curr Pharm Des. 2019;25(30):3248-3256. doi: 10.2174/1381612825666190816233755.

Abstract

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.

Keywords: Disulfiram; anticancer agents; cancer; clinical trials; drug delivery; molecular targets..

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Disulfiram / pharmacology*
  • Humans
  • Neoplasm Metastasis / drug therapy
  • Neoplasms / drug therapy*
  • Neoplastic Stem Cells / drug effects
  • Proteasome Endopeptidase Complex
  • Proteasome Inhibitors / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Ubiquitin-Protein Ligase Complexes / antagonists & inhibitors*

Substances

  • Proteasome Inhibitors
  • Reactive Oxygen Species
  • Ubiquitin-Protein Ligase Complexes
  • Proteasome Endopeptidase Complex
  • Disulfiram