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 (AR) pathway remain the standard therapy for PCa patients. Enzalutamide (ENZ), a second-generation AR inhibitor, was developed to treat castration-resistant prostate cancer (CRPC). However, while patients initially respond to ENZ, drug resistance typically develops within a few months. Artesunate (ART), a semi-synthetic derivative of the Artemisinin plant, is approved for anti-malaria treatment. In this study, we conducted an FDA-approved drug screening and identified Artesunate as a potential candidate for overcoming ENZ resistance in prostate cancer (ENZ-R 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.