Despite the current advances in the treatment for prostate cancer, the patients often develop resistance to the conventional therapeutic interventions. Therapy-induced drug resistance and tumor progression have been associated with cellular plasticity acquired due to reprogramming at the molecular and phenotypic levels. The plasticity of the tumor cells is mainly governed by two factors: cell-intrinsic and cell-extrinsic. The cell-intrinsic factors involve alteration in the genetic or epigenetic regulators, while cell-extrinsic factors include microenvironmental cues and drug-induced selective pressure. Epithelial-mesenchymal transition (EMT) and stemness are two important hallmarks that dictate cellular plasticity in multiple cancer types including prostate. Emerging evidence has also pinpointed the role of tumor cell plasticity in driving anti-androgen induced neuroendocrine prostate cancer (NEPC), a lethal and therapy-resistant subtype. In this review, we discuss the role of cellular plasticity manifested due to genetic, epigenetic alterations and cues from the tumor microenvironment, and their role in driving therapy resistant prostate cancer.

尽管目前前列腺癌的治疗取得了进展，但患者常常对传统的治疗干预产生耐药性。治疗诱导的耐药性和肿瘤进展与由于分子和表型水平的重编程而获得的细胞可塑性相关。肿瘤细胞的可塑性主要受细胞内在和细胞外在两个因素的影响。细胞内在因素涉及遗传或表观遗传调节因子的改变，而细胞外在因素包括微环境线索和药物诱导的选择压力。上皮间质转化（EMT）和干性是决定包括前列腺在内的多种癌症类型的细胞可塑性的两个重要标志。新的证据还明确了肿瘤细胞可塑性在驱动抗雄激素诱导的神经内分泌前列腺癌（NEPC）中的作用，NEPC是一种致命且耐药的亚型。在这篇综述中，我们讨论了由于遗传、表观遗传改变和肿瘤微环境线索而表现出的细胞可塑性的作用，以及它们在驱动治疗耐药性前列腺癌中的作用。