Current androgen deprivation induces androgen receptor-independent prostate cancer via HGF and Wnt activation to foster nuclear export and ribosome biogenesis [scRNA-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 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 PCa. Understanding the mechanisms for DNPC will directly improve clinical outcomes. Two sequencing datasets were analyzed containing prostatic adenocarcinoma and carcinoma tissues

为通过残余雄激素抑制雄激素受体（AR, Androgen Receptor）介导的肿瘤生长复燃，近数十年来科研人员已开发出效力更强的雄激素受体拮抗剂与雄激素合成抑制剂。尽管此类第二代拮抗剂/抑制剂在临床中展现出一定疗效，但同时也诱导出更多样的去势抵抗性前列腺癌（CRPC, Castration-Resistant Prostate Cancer）表型。具体而言，在接受阿比特龙与恩扎卢胺治疗的去势抵抗性前列腺癌患者中，常出现雄激素受体阴性且神经内分泌（NE, Neuroendocrine）阴性的前列腺癌（PC, Prostate Cancer）细胞亚群DNPC，该亚群会提升转移性去势抵抗性前列腺癌的发病率与前列腺癌（PCa, Prostate Cancer）患者的死亡率。阐明DNPC的相关致病机制，将直接改善临床诊疗结局。本研究分析了两份包含前列腺腺癌组织与癌组织的测序数据集。