Prostate cancer is one of the most prevalent cancers in men, and there is no cure when it advances to a late stage. Antiandrogens are routinely used in clinics for prostate cancer treatment, and darolutamide (Daro) is the latest FDA-approved antiandrogen drug.1 Despite its efficacy, potential drug resistance poses significant challenges in the clinical setting. This study seeks to uncover the molecular mechanisms behind darolutamide resistance and identify potential therapeutic targets to overcome this resistance.