Artesunate enhances the efficacy of enzalutamide in advanced prostate cancer

TL;DR

Artesunate, a malaria drug, can improve the effectiveness of enzalutamide in treating resistant prostate cancer by targeting c-Myc.

Contribution

Artesunate is identified as a novel candidate to overcome enzalutamide resistance via c-Myc degradation.

Findings

Artesunate enhances enzalutamide's efficacy by degrading c-Myc.

c-Myc is significantly involved in enzalutamide resistance in prostate cancer.

FDA-approved drug screening identified artesunate as a potential therapeutic strategy.

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.

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