A new study, led by Jiri Bartek (Karolinska Institutet/SciLifeLab) has explored the potential for using disulfiram, also known as Antabuse – an old alcohol-aversion drug, to treat cancer. The results show an anti-cancer effect of the substance in a range of cancers including colon, prostate and breast cancer. The results are published in Nature.
Cancer incidence is rising and this global challenge is further exacerbated by tumour resistance to available medicines. A promising approach to meet the need for improved cancer treatment is repurposing of existing drugs. The current paper studies the effect of the active substance in Antabuse, disulfiram, on cancer and demonstrates both a reduced risk of dying from a diagnosed cancer disease and an explanatory biological mechanism of action.
The nationwide investigation of over 3 000 Danish individuals aged 35-85 years shows that patients who continued to use disulfiram also after they were diagnosed with cancer had a lower risk of dying from their disease compared to those who stopped using the drug upon diagnosis. This is in line with previous preclinical research, indicating that disulfiram has anti-cancer activity. The new paper also identifies a metabolite of the drug, which is responsible for its effects on cancer, and reveals the molecule NPL4 to be the target of disulfiram’s tumour-suppressing effects. NPL4 plays a role in controlling the turnover of proteins involved in multiple regulatory and stress-response pathways in cells. The previous lack of a defined mechanism of action has prevented the repurposing of disulfiram as an anti-cancer drug, but as this study provides also candidate biomarkers for analysis of disulfiram’s effect on cells and tissues, a framework for this process has been created.
The substance disulfiram, commercially sold as Antabuse) has been used for several decades to treat alcoholic abuse. If alcoholics drink even a little liquor after taking the drug, they will experience a wave of unpleasant symptoms, ranging from throbbing head pain and vomiting to chest pain and anxiety.