Disulfiram: A novel repurposed drug for cancer therapy

• Published in: Chinese medical journal 2024-06, Vol.137 (12), p.1389-1398
• Main Authors: Zeng, Min, Wu, Baibei, Wei, Wenjie, Jiang, Zihan, Li, Peiqiang, Quan, Yuanting, Hu, Xiaobo
• Format: Article
• Language: English
• Subjects: Alcohol use; Angiogenesis; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antioxidants; Apoptosis; Bone cancer; Breast cancer; Cancer therapies; Cell cycle; Cell death; Copper; Cytotoxicity; Disulfiram - pharmacology; Disulfiram - therapeutic use; Drug Repositioning; Drug resistance; FDA approval; Ferroptosis; Health risks; Humans; Kinases; Liver cancer; Metastasis; Neoplasms - drug therapy; Neoplastic Stem Cells - drug effects; NF-kappa B - metabolism; Oxidative stress; Prostate cancer; Proteins; Public health; Reactive oxygen species; Reactive Oxygen Species - metabolism; Review; Signal Transduction - drug effects; Thyroid cancer
• ISSN: 0366-6999; 2542-5641; 2542-5641
• DOI: 10.1097/CM9.0000000000002909

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.