Research press release





今回、Jiri Bartekたちの研究グループは、ジスルフィラムの効果を詳しく解明するため、2000~2013年に初めてがんと診断された3000人以上のデンマーク人(35~85歳)を対象として、ジスルフィラムの使用に伴うがんの転帰を調べた。その結果わかったのは、ジスルフィラムの使用を続けた患者のがん関連死が、がんの診断後にジスルフィラムの使用を中止した患者のがん関連死よりも少なかったことで、こうしたジスルフィラムの効果は、大腸がん、前立腺がん、乳がんなどさまざまながんにおいて観察された。さらにマウスと細胞株を使った研究も行われ、腫瘍に蓄積し、抗がん作用を持つジスルフィラムの代謝物が同定され、この代謝物が作用してがん細胞を死滅させる分子経路も明らかになった。


An alcohol-abuse treatment is shown to reduce the risk of death from cancer in a study published online in Nature this week. These findings suggest that the alcohol-aversion drug disulfiram (Antabuse) could potentially be repurposed as an anti-cancer drug.

Previous research has indicated that disulfiram, a drug used for over six decades as a treatment for alcohol dependence, has anti-cancer activity. However, the absence of a defined mechanism of action and failure to identify a specific molecular target on which the drug acts have prevented the repurposing of disulfiram as an anti-cancer treatment.

To understand more about the effects of disulfiram, Jiri Bartek and colleagues investigated cancer outcomes associated with disulfiram use in over 3,000 Danish individuals aged 35-85 years with a first-time diagnosis of cancer between 2000 and 2013. They found that cancer-related deaths were reduced in patients who continued to use disulfiram compared with those who stopped using the drug after their diagnosis; this effect was seen in a range of cancers including colon, prostate and breast cancer. Further studies in mice and cell lines identified a metabolite of disulfiram that accumulates in tumours and exerts an anti-cancer effect, and revealed a molecular pathway through which the metabolite acts to kill cancer cells.

Developing new medicines is a costly process, often taking a long time and with high failure rates. Therefore, repurposing drugs that are already approved for treatment, such as disulfiram, as candidates for cancer therapy is an attractive alternative, as much of the testing (such as safety in patients) has already been done.

doi: 10.1038/nature25016

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