Terbinafine prevents colorectal cancer growth by inducing dNTP starvation and reducing immune suppression

Li-Peng Hu, Wuqing Huang, Xu Wang, Chunjie Xu, Wei-Ting Qin, Dongxue Li, Guangang Tian, Qing Li, Yaoqi Zhou, Suyuan Chen, Hui-Zhen Nie, Yujun Hao, Jian Song, Xue-Li Zhang, Jan Sundquist, Kristina Sundquist, Jun Li, Shu-Heng Jiang, Zhi-Gang Zhang, Jianguang Ji

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review


Existing evidence indicates that gut fungal dysbiosis might play a key role in the pathogenesis of colorectal cancer (CRC). We sought to explore whether reversing the fungal dysbiosis by terbinafine, an approved antifungal drug, might inhibit the development of CRC. A population-based study from Sweden identified a total of 185 patients who received terbinafine after their CRC diagnosis and found that they had a decreased risk of death (hazard ratio=0.50) and metastasis (hazard ratio=0.44) compared with patients without terbinafine administration. In multiple mouse models of CRC, administration of terbinafine decreased the fungal load, the fungus-induced myeloid-derived suppressor cell (MDSC) expansion, and the tumor burden. Fecal microbiota transplantation from mice without terbinafine treatment reversed MDSC infiltration and partially restored tumor proliferation. Mechanistically, terbinafine directly impaired tumor cell proliferation by reducing the ratio of nicotinamide adenine dinucleotide phosphate (NADP+) to reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), suppressing the activity of glucose-6-phosphate dehydrogenase (G6PD), resulting in nucleotide synthesis disruption, deoxyribonucleotide (dNTP) starvation and cell cycle arrest. Collectively, terbinafine can inhibit CRC by reversing fungal dysbiosis, suppressing tumor cell proliferation, inhibiting fungus-induced MDSC infiltration, and restoring antitumor immune response.

Sidor (från-till)3284-3299
TidskriftMolecular Therapy
Tidigt onlinedatum2022 juni 27
StatusPublished - 2022

Bibliografisk information

Copyright © 2022 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Ämnesklassifikation (UKÄ)

  • Cancer och onkologi


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