The success of next-generation androgen receptor (AR) pathway inhibitors, such as abiraterone acetate and enzalutamide, in treating prostate cancer has been hampered by the emergence of drug resistance. This acquired drug resistance is driven, in part, by the ability of prostate cancer cells to change their phenotype to adopt AR-independent pathways for growth and survival. Around one-quarter of resistant prostate tumours comprise cells that have undergone cellular reprogramming to become AR-independent and to acquire a continuum of neuroendocrine characteristics. These highly aggressive and lethal tumours, termed neuroendocrine prostate cancer (NEPC), exhibit reactivation of developmental programmes that are associated with epithelial–mesenchymal plasticity and acquisition of stem-like cell properties. In the past few years, our understanding of the link between lineage plasticity and an emergent NEPC phenotype has considerably increased. This new knowledge can contribute to novel therapeutic modalities that are likely to improve the treatment and clinical management of aggressive prostate cancer.

耐药性的出现阻碍了下一代雄激素受体（AR）途径抑制剂（例如乙酸阿比特龙酯和enzalutamide）在治疗前列腺癌中的成功。这种获得性抗药性部分地受到前列腺癌细胞改变其表型以采用非AR依赖性途径进行生长和存活的能力的驱动。大约四分之一的耐药前列腺肿瘤包含已进行细胞重编程以变得不依赖AR并获得连续的神经内分泌特征的细胞。这些高度侵袭性和致死性的肿瘤称为神经内分泌前列腺癌（NEPC），表现出与上皮-间充质可塑性和干样细胞特性获得有关的发育程序的重新激活。在过去的几年里，我们对谱系可塑性和新兴的NEPC表型之间的联系的了解已大大增加。这一新知识可以促进可能改善侵略性前列腺癌的治疗和临床管理的新型治疗方式。