The magic bullet: Niclosamide
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1004978/full |
| _version_ | 1811219427897638912 |
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| author | Haowen Jiang Albert M. Li Albert M. Li Jiangbin Ye Jiangbin Ye Jiangbin Ye |
| author_facet | Haowen Jiang Albert M. Li Albert M. Li Jiangbin Ye Jiangbin Ye Jiangbin Ye |
| author_sort | Haowen Jiang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T07:26:42Z |
| format | Article |
| id | doaj.art-185f2d556b834ac4add12e56e9990e04 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T07:26:42Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-185f2d556b834ac4add12e56e9990e042022-12-22T03:42:10ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.10049781004978The magic bullet: NiclosamideHaowen Jiang0Albert M. Li1Albert M. Li2Jiangbin Ye3Jiangbin Ye4Jiangbin Ye5Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, United StatesDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, United StatesCancer Biology Program, Stanford University School of Medicine, Stanford, CA, United StatesDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, United StatesCancer Biology Program, Stanford University School of Medicine, Stanford, CA, United StatesStanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, United StatesThe 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.1004978/fullniclosamidemitochondrial uncouplermetabolismepigeneticsanti-tumor effectoncogenic pathways |
| spellingShingle | Haowen Jiang Albert M. Li Albert M. Li Jiangbin Ye Jiangbin Ye Jiangbin Ye The magic bullet: Niclosamide Frontiers in Oncology niclosamide mitochondrial uncoupler metabolism epigenetics anti-tumor effect oncogenic pathways |
| title | The magic bullet: Niclosamide |
| title_full | The magic bullet: Niclosamide |
| title_fullStr | The magic bullet: Niclosamide |
| title_full_unstemmed | The magic bullet: Niclosamide |
| title_short | The magic bullet: Niclosamide |
| title_sort | magic bullet niclosamide |
| topic | niclosamide mitochondrial uncoupler metabolism epigenetics anti-tumor effect oncogenic pathways |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1004978/full |
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