Current androgen deprivation induces androgen receptor-independent prostate cancer via HGF and Wnt activation to foster nuclear export and ribosome biogenesis [RNA-seq]
To inhibit the re-activation of AR-promoted tumor growth via residual androgens, more potent AR antagonists and inhibitors for androgen synthesis have been developed in the decades. While these second-generation antagonists/inhibitors showed some effectiveness clinically, they also induced more diverse castration-resistant prostate cancer (CRPC) phenotypes. Specifically, a subpopulation of AR- and neuroendocrine (NE)-null PC cells, DNPC, occurs frequently in CRPC patients treated with abiraterone and enzalutamide, increasing metastatic CRPC incidences and the mortality of prostate adenocarcinoma (PCa). Understanding the mechanisms for DNPC will directly improve clinical outcomes. Overall design: Two or Three replicates were included in each group.