Targeting adenocarcinoma and enzalutamide-resistant prostate cancer using the novel anti-androgen inhibitor ADA-308

Prostate cancer is a leading cause of cancer-related death among men globally. It often develops resistance to standard androgen deprivation therapy and androgen receptor (AR) pathway inhibitors such as enzalutamide. This resistance highlights the urgent need for novel therapeutic strategies. ADA-308 emerges as a promising candidate, demonstrating potent inhibition of both AR-sensitive adenocarcinoma as well as enzalutamide-resistant prostate cancer cell lines. Our studies reveal that ADA-308 effectively blocks AR activity, including nuclear localization, and inhibits cell proliferation in vitro. Furthermore, ADA-308 demonstrates remarkable efficacy in vivo, showcasing a robust antitumor response in enzalutamide-resistant models. These findings establish ADA-308’s role as a potent AR inhibitor that overcomes resistance to AR-targeted therapies and highlight its potential as a novel therapeutic approach in advanced prostate cancer management. LNCaP cell lines were cultured in RPMI-1640 media plus 5% FBS treated with10µmol/L enzalutamide or ADA-308 for 72 hours. Cells were collected for RNA sequencing.