Artesunate enhances the efficacy of enzalutamide in advanced prostate cancer
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.
Authors
- Qiou Wei (ORCID: https://orcid.org/0000-0001-6752-8692)
- Qiongsi Zhang (ORCID: https://orcid.org/0000-0002-6234-5034)
- Sally R. Ellingson (ORCID: https://orcid.org/0009-0004-3527-4041)
- Yanquan Zhang (ORCID: https://orcid.org/0000-0003-3527-9972)
- Yifan Kong (ORCID: https://orcid.org/0000-0002-5650-8079)
- Daheng He (ORCID: https://orcid.org/0000-0003-0399-2466)
- Chi Chiu Wang (ORCID: https://orcid.org/0000-0002-3928-7278)
- Fengyi Mao (ORCID: https://orcid.org/0000-0001-7785-6606)
- Chaohao Li (ORCID: https://orcid.org/0000-0001-5975-3937)
- Xinyi Wang (ORCID: https://orcid.org/0000-0002-9082-258X)
- Zhiguo Li (ORCID: https://orcid.org/0000-0002-6869-2766)
- Jinghui Liu (ORCID: https://orcid.org/0000-0002-9676-1538)
- Xiaoqi Liu (ORCID: https://orcid.org/0000-0002-6613-1746)
- Ruixin Wang (ORCID: https://orcid.org/0000-0003-2624-1593)
Institutions
- University of Kentucky (US)
- Markey Cancer Center (US)
Publication Details
- Journal
- Journal of Biological Chemistry
- Published
- 2025-03-28
- DOI
- https://doi.org/10.1016/j.jbc.2025.108458
- Primary Topic
- Prostate Cancer Treatment and Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Foundation for the National Institutes of Health
- National Institutes of Health
- National Cancer Institute