【摘要】 新药研发周期长、成本高，并且失败几率大，老药新用成为药物研发中非常重要的策略。双硫仑（Disulfiram, DSF）是用于治疗酒精成瘾的药物，安全性和耐受性良好，价格低廉。大量研究显示DSF能诱导多种肿瘤细胞死亡，并且与铜离子(Cu²⁺)联合能增强其抗肿瘤作用。DSF/Cu通过多种机制发挥抗肿瘤作用，包括：上调活性氧（Reactive oxygen species, ROS）和内质网应激诱导癌细胞凋亡；靶向NPL4抑制蛋白酶体活性；靶向乙醛脱氢酶（Acetaldehyde dehydrogenase, ALDH）抑制肿瘤干细胞；抑制肿瘤的血管生成和上皮-间充质转化（Epithelial mesenchymal transition, EMT）途径。然而，目前关于DSF/Cu的12项临床研究并未获得可靠疗效，这与DSF和Cu²⁺的口服方式有关。文章对DSF/Cu用于癌症治疗的研究进行综述，并简介有关的递送策略，希望对以DSF/Cu为基础的肿瘤治疗有所启示。更多还原

【Abstract】 New drugs take a long time to develop, cost a lot, and fail a lot.New use of old drugs has become a very important strategy in drug research and development.Disulfiram（DSF） was a drug used in the treatment of alcohol addiction, which was safe and well tolerated and inexpensive.A large number of studies have shown that DSF can induce the death of various tumor cells, and its anti-tumor effect can be enhanced in combination with Copper ion(Cu²⁺).DSF/Cu exerts antitumor activity through various mechanisms, including: Up-regulation of reactive oxygen species（ROS） and endoplasmic reticulum stress induces apoptosis in cancer cells; Targeting NPL4 inhibits proteasome activity; Targeting acetaldehyde dehydrogenase（ALDH） to inhibit tumor stem cells; Inhibits tumor angiogenesis and epithelial-mesenchymal transition（EMT） pathways.However, the current 12 clinical studies on DSF/Cu have not obtained reliable efficacy, which was related to the oral way of DSF and Cu²⁺.The research of DSF/Cu in cancer therapy was reviewed and the relevant delivery strategies were briefly introduced in the hope of providing some enlightenment for DSF/Cu-based tumor therapy.更多还原