Artesunate enhances the efficacy of enzalutamide in advanced prostate cancer

Authors

Xinyi Wang, University of KentuckyFollow
Jinghui Liu, University of KentuckyFollow
Fengyi Mao, University of Kentucky
Yifan Kong, University of KentuckyFollow
Qiongsi Zhang, University of KentuckyFollow
Chaohao Li, University of KentuckyFollow
Daheng He, University of KentuckyFollow
Chi Wang, University of KentuckyFollow
Yanquan Zhang, University of KentuckyFollow
Ruixin Wang, University of KentuckyFollow
Sally R. Ellingson, University of KentuckyFollow
Qiou Wei, University of KentuckyFollow
Zhiguo Li, University of KentuckyFollow
Xiaoqi Liu, University of KentuckyFollow

Abstract

Prostate cancer (PCa) is one of the leading causes of death among men worldwide. Treatments targeting the androgen receptor pathway remain the standard therapy for PCa patients. Enzalutamide (ENZ), a second-generation androgen receptor inhibitor, was developed to treat castration-resistant prostate cancer. However, while patients initially respond to ENZ, drug resistance typically develops within a few months. Artesunate (ART), a semisynthetic derivative of the Artemisinin plant, is approved for antimalaria treatment. In this study, we conducted an FDA-approved drug screening and identified ART as a potential candidate for overcoming ENZ resistance in PCa. Mechanistically, ART induces the degradation of c-Myc, enhancing the efficacy of ENZ. Additionally, patient dataset analysis revealed that c-Myc plays a significant role in developing ENZ resistance. To summarize, these findings suggest a novel therapeutic strategy for ENZ-resistant prostate cancer.

Document Type

Article

Publication Date

3-2025

Notes/Citation Information

© 2025 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.jbc.2025.108458

Funding Information

This work was supported by the National Institutes of Health, National Cancer Institute [R01 CA256893, R01 CA264652, R01 CA157429, R01 CA272483, P30 CA177558, R01CA266579]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Repository Citation

Wang, Xinyi; Liu, Jinghui; Mao, Fengyi; Kong, Yifan; Zhang, Qiongsi; Li, Chaohao; He, Daheng; Wang, Chi; Zhang, Yanquan; Wang, Ruixin; Ellingson, Sally R.; Wei, Qiou; Li, Zhiguo; and Liu, Xiaoqi, "Artesunate enhances the efficacy of enzalutamide in advanced prostate cancer" (2025). Markey Cancer Center Faculty Publications. 426.
https://uknowledge.uky.edu/markey_facpub/426