Disulfiram: a novel repurposed drug for cancer therapy

Cancer is a major health issue worldwide and the global burden of cancer is expected to reduce the costs of treatment as well as prolong the survival time. One of the promising approaches is drug repurposing, because it reduces costs and shortens the production cycle of research and development. Dis...

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Veröffentlicht in:Cancer chemotherapy and pharmacology Jg. 87; H. 2; S. 159 - 172
Hauptverfasser: Lu, Chen, Li, Xinyan, Ren, Yongya, Zhang, Xiao
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2021
Springer Nature B.V
Schlagworte:
Alcoholism
Aldehyde dehydrogenase
Brain cancer
Breast cancer
Cancer Research
Cancer therapies
Cell death
Chemotherapy
Clinical trials
Disulfiram
Drug abuse
Endoplasmic reticulum
Glioblastoma
Hepatocytes
Immobilization
Intracellular signalling
Liver cancer
Localization
Medicine
Medicine & Public Health
Melanoma
Metastases
NF-κB protein
Non-small cell lung carcinoma
Oncology
Pancreatic cancer
Phagocytosis
Pharmacology/Toxicology
Proteasomes
Radiation
Review Article
Signal transduction
Stem cells
Tumors
Disulfiram
Clinical trials
Tumour
Cancer stem cells
ISSN:0344-5704, 1432-0843, 1432-0843
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Zusammenfassung:Cancer is a major health issue worldwide and the global burden of cancer is expected to reduce the costs of treatment as well as prolong the survival time. One of the promising approaches is drug repurposing, because it reduces costs and shortens the production cycle of research and development. Disulfiram (DSF), which was originally approved as an anti-alcoholism drug, has been proven safe and shows the potential to target tumours. Its anti-tumour effect has been reported in many preclinical studies and recently on seven types of cancer in humans: non-small cell lung cancer (NSCLC), liver cancer, breast cancer, prostate cancer, pancreatic cancer, glioblastoma (GBM) and melanoma and has a successful breakthrough in the treatment of NSCLC and GBM. The mechanisms, particularly the intracellular signalling pathways, still remain to be completely elucidated. As shown in our previous study, DSF inhibits NF-kB signalling, proteasome activity, and aldehyde dehydrogenase (ALDH) activity. It induces endoplasmic reticulum (ER) stress and autophagy and has been used as an adjuvant therapy with irradiation or chemotherapy drugs. On the other hand, DSF not only kills the normal cancer cells but also has the ability to target cancer stem cells, which provides a new approach to prevent tumour recurrence and metastasis. Furthermore, other researchers have reported the ability of DSF to bind to nuclear protein localization protein 4 (NPL4), induce its immobilization and dysfunction, ultimately leading to cell death. Here, we provide an overview of DSF repurposing as a treatment in preclinical studies and clinical trials, and review studies describing the mechanisms underlying its anti-neoplastic effects.
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ISSN:0344-5704
1432-0843
1432-0843
DOI:10.1007/s00280-020-04216-8