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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.

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