An international team led by researchers from the Institute of Molecular and Translational Medicine (IMTM), at the Faculty of Medicine and Dentistry of Palacky University in Olomouc, published in one of the most prestigious scientific journals “Nature” a work focused on a drug used to treat alcohol dependence (disulfiram, Antabus) in its future use for the treatment of cancer.
A team of researchers from the IMTM led by Professor Jiří Bártek and other colleagues from five countries (Denmark, Sweden, Switzerland, USA and Canada) combined laboratory, preclinical and epidemiological research and found that disulfiram, a cheap drug for many decades sold under the brand name Antabus and used to treat alcohol dependence, has extraordinary anti-tumor effects. The work is based on an epidemiological study carried out on Danish patients – alcoholics who have been diagnosed with malignancies. Patients who continued to use disulfiram even after tumor diagnosis showed that they had a significantly lower risk of death than patients who discontinued use. These data, pointing to the potential anti-tumor effect of disulfiram, have stimulated further molecular biological research to target the drug to tumor cells. Disulfiram has been shown to be metabolized in the human body by the contribution of copper to another substance that accumulates in tumor cells and binds to NPL4 protein. This causes immobilization and loss of functionality. Functional protein NPL4 is an essential part of an important molecular pathway (the so-called p97 pathway) that helps cells cope with stress caused by the accumulation of damaged proteins in the endoplasmic reticulum. Tumor cells are normally exposed to a huge overproduction of defective proteins. The fully functional p97 / NPL4 pathway is so important for their survival and is considered an attractive target for future treatment. Disulfiram, or its active metabolite, induced defect in the p97 pathway was a breakthrough finding that with knowledge of the molecular target allows future personalization of treatment with disulfiram and its indication to patients most likely with therapeutic response. In this respect, scientists from IMTM and Olomouc University Hospital continue their research and the effects of disulfiram in combination with copper are being verified in a clinical study that is open to patients with metastatic breast cancer.
The article called “Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4″ is available on the Nature magazine website.
The original press release and further information (in Czech) is available on the IMTM website.