Division of Cancer Biology, Laboratory Animal Center, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
School of Basic Medical Sciences, Medical College of Yan'an University, 580 Bao-Ta Street, 716000, Yanan, China.
Lab Invest. 2022 Apr;102(4):332-340. doi: 10.1038/s41374-021-00716-0. Epub 2021 Dec 22.
Prostate cancer is the most common cancer among men and has a high incidence and associated mortality worldwide. It is an androgen-driven disease in which tumor growth is triggered via ligand-mediated signaling through the androgen receptor (AR). Recent evidence suggests that the widespread use of effective AR pathway inhibitors may increase the occurrence of neuroendocrine prostate cancer (NEPC), an aggressive and treatment-resistant AR-negative variant; however, mechanisms controlling NEPC development remain to be elucidated. Various preclinical models have recently been developed to investigate the mechanisms driving the NEPC differentiation. In the present study, we summarized strategies for the development of NEPC models and proposed a novel method for model evaluation, which will help in the timely and accurate identification of NEPC by virtue of its ability to recapitulate the heterogeneity of prostate cancer. Moreover, we discuss the origin and the mechanism of NEPC. The understanding of the regulatory network mediating neuroendocrine differentiation presented in this review could provide valuable insights into the identification of novel drug targets for NEPC as well as into the causes of antiandrogenic drug resistance.
前列腺癌是男性中最常见的癌症，在全球范围内发病率和相关死亡率都很高。它是一种雄激素驱动的疾病，其中肿瘤生长是通过配体介导的信号通过雄激素受体 (AR) 触发的。最近的证据表明，广泛使用有效的 AR 途径抑制剂可能会增加神经内分泌前列腺癌 (NEPC) 的发生，这是一种侵袭性和治疗抵抗的 AR 阴性变体;然而，控制 NEPC 发展的机制仍有待阐明。最近已经开发了各种临床前模型来研究驱动 NEPC 分化的机制。在本研究中，我们总结了开发 NEPC 模型的策略，并提出了一种新的模型评估方法，该方法将有助于通过其重现前列腺癌异质性的能力来及时准确地识别 NEPC。此外，我们还讨论了 NEPC 的起源和机制。本文综述中提出的调节神经内分泌分化的调控网络的理解，可为 NEPC 的新型药物靶点的鉴定以及抗雄激素药物耐药的原因提供有价值的见解。
