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Teaching an Old Drug New Tricks: Antabuse Shifts from Alcoholism to Cancer

A recent article in Science discusses how antabuse, a drug with a long history of treating alcoholism, finds new applications in fighting cancer.

Antabuse (disulfiram) has been used to treat alcoholism for decades. It discourages alcohol abuse by provoking nausea when consuming even small amounts of alcohol. Case reports and lab studies dating back to the 1970s suggest that Antabuse may also have anti-cancer properties. However, there hasn’t been much recent research into its anti-cancer properties, and scientists have puzzled over its mechanism of action for many years.

A news article in Science reports on a recent study in this field. Researchers in Denmark, the Czech Republic, and the United States pored over patient data and performed mice experiments to determine the effect of Antabuse on the progression of cancer. Their work was recently published in Nature. Searching through Denmark’s cancer registry, they discovered that out of 3000 patients who had taken Antabuse, the death rate due to cancer was 34% lower in those who stayed on the drug compared to those who came off of it.

Researchers continued to investigate these anti-cancer properties in mice studies, where the drug was shown to slow the growth of tumours in breast cancer, especially when administered with copper. These mice experiments also shed light on the drug’s mechanism of action. When the drug is broken down, one of its metabolites combines with copper and blocks the ubiquitin-proteasome system of the cell, which is normally responsible for getting rid of excess proteins. The cells then die due to protein overload. Normal cells aren’t affected by Antabuse in this manner, and it seems to be due to differences in the way Antabuse is broken down in cancer cells. Researchers found that the copper metabolite is ten times more likely to be found in tumours than in healthy tissue.

As with many cancer treatments, experts are quick to caution that Antabuse is not a definitive cure. However, its long history on the market could make it an inexpensive treatment to extend the lifespan of patients with metastatic cancer. Researchers are now launching multiple trials to determine its effect on metastatic breast, colon, and brain cancers.

Written by Agustin Dominguez Iino, BSc

References:

(1) Kaiser, Jocelyn. An old drug for alcoholism finds new life as cancer treatment. Science. 06 December 2017. http://www.sciencemag.org/news/2017/12/old-drug-alcoholism-finds-new-life-cancer-treatment
(2) Skrott et al. Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4. Nature. 14 December 2017. 552(194–199). doi:10.1038/nature25016

 

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