Jiang Haowen, Li Albert M, Ye Jiangbin
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, United States.
Cancer Biology Program, Stanford University School of Medicine, Stanford, CA, United States.
Front Oncol. 2022 Nov 21;12:1004978. doi: 10.3389/fonc.2022.1004978. eCollection 2022.
The term 'magic bullet' is a scientific concept proposed by the German Nobel laureate Paul Ehrlich in 1907, describing a medicine that could specifically and efficiently target a disease without harming the body. Oncologists have been looking for a magic bullet for cancer therapy ever since. However, the current therapies for cancers-including chemotherapy, radiation therapy, hormone therapy, and targeted therapy-pose either pan-cytotoxicity or only single-target efficacy, precluding their ability to function as a magic bullet. Intriguingly, niclosamide, an FDA-approved drug for treating tapeworm infections with an excellent safety profile, displays broad anti-cancer activity in a variety of contexts. In particular, niclosamide inhibits multiple oncogenic pathways such as Wnt/β-catenin, Ras, Stat3, Notch, E2F-Myc, NF-κB, and mTOR and activates tumor suppressor signaling pathways such as p53, PP2A, and AMPK. Moreover, niclosamide potentially improves immunotherapy by modulating pathways such as PD-1/PDL-1. We recently discovered that niclosamide ethanolamine (NEN) reprograms cellular metabolism through its uncoupler function, consequently remodeling the cellular epigenetic landscape to promote differentiation. Inspired by the promising results from the pre-clinical studies, several clinical trials are ongoing to assess the therapeutic effect of niclosamide in cancer patients. This current review summarizes the functions, mechanism of action, and potential applications of niclosamide in cancer therapy as a magic bullet.
“神奇子弹”一词是德国诺贝尔奖获得者保罗·埃尔利希在1907年提出的一个科学概念，指的是一种能够特异性且高效地靶向疾病而不损害身体的药物。从那时起，肿瘤学家们就一直在寻找用于癌症治疗的神奇子弹。然而，目前的癌症治疗方法——包括化疗、放疗、激素治疗和靶向治疗——要么具有泛细胞毒性，要么只有单靶点疗效，这使得它们无法起到神奇子弹的作用。有趣的是，氯硝柳胺是一种经美国食品药品监督管理局批准用于治疗绦虫感染且安全性极佳的药物，在多种情况下都显示出广泛的抗癌活性。特别是，氯硝柳胺能抑制多种致癌途径，如Wnt/β-连环蛋白、Ras、Stat3、Notch、E2F-Myc、NF-κB和mTOR，并激活肿瘤抑制信号通路，如p53、PP2A和AMPK。此外，氯硝柳胺可能通过调节PD-1/PDL-1等途径来改善免疫治疗。我们最近发现，氯硝柳胺乙醇胺（NEN）通过其解偶联功能重新编程细胞代谢，从而重塑细胞表观遗传景观以促进分化。受临床前研究取得的令人鼓舞的结果启发，目前正在进行多项临床试验以评估氯硝柳胺对癌症患者的治疗效果。本综述总结了氯硝柳胺作为神奇子弹在癌症治疗中的功能、作用机制和潜在应用。
