杜君　陈倩倩　杨庆



去势治疗诱导的神经内分泌前列腺癌的研究进展*

杜君陈倩倩杨庆

摘要转移性前列腺癌行去势治疗（androgen-deprivation therapy，ADT）后将逐渐发展为去势抵抗性前列腺癌（castration-resistant prostate cancer，CRPC）。神经内分泌前列腺癌（neuroendocrine prostate cancer，NEPC）是CRPC的极差预后亚型，多由前列腺癌细胞发生神经内分泌分化（neuroendocrine differentiation，NED）引起，放化疗效果较差，平均生存期不到1年，约占因CRPC患者死亡的25%，目前其分子机制研究较有限。进一步研究NEPC发生的分子机制将为NEPC治疗药物的开发与应用提供新的思路。

关键词前列腺癌去势治疗神经内分泌分化

*本文课题受国家自然科学青年科学基金项目（编号：81502218）资助

Research progress on neuroendocrine prostate cancer induced by androgen deprivation therapy

Jun DU, Qianqian CHEN, Qing YANG
Correspondence to: Qing YANG; E-mail: yuro2008@163.com
Department of Urological Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
This work was supported by the Youth Science Funds of the National Natural Science Foundation of China（No.81502218）

Abstract Patients with metastatic prostate cancer are typically managed with androgen deprivation therapy.Most patients initially respond to treatment, but many eventually develop castration-resistant prostate cancer.Neuroendocrine prostate cancer（NEPC）is a highly aggressive subtype of castration-resistant prostate cancer, which often results from neuroendocrine differentiation of prostate cancer cells.NEPC has a dismal outcome with an average survival of less than 1 year and exhibits less response to radiochemotherapy.At least 25% of patients with lethal castration-resistant prostate cancer are predicted to eventually develop this type of highly-aggressive NEPC.However, research on the molecular mechanism of NEPC is limited; thus, further studies are needed to explore the development and application of anticancer drugs for NEPC.

Keywords:prostate cancer, androgen deprivation therapy, neuroendocrine differentiation

前列腺癌是男性泌尿生殖系统常见恶性肿瘤之一，目前在美国发病率已超过肺癌，位居男性恶性肿瘤第1位［1］。随着我国人民生活方式西化及前列腺癌筛查手段的普及，发病率与癌症检出率也逐年升高［2］。大多数前列腺癌发现时即为转移性前列腺癌，因此5年生存率低和病死率高成为我国前列腺癌流行病学的主要特点。去势治疗（ADT）是转移性前列腺癌的主要治疗方法，于1941年由Huggins和Hodges基于前列腺癌的雄激素依赖性提出［3］。大多数转移性前列腺癌患者初期均对ADT有效，但经过中位时间12～18个月后，几乎所有接受ADT治疗患者的病变都将逐渐发展为去势抵抗性前列腺癌［4］。

神经内分泌前列腺癌（NEPC）多由ADT引起，是去势抵抗性前列腺癌（CRPC）的极差预后亚型，约占因CRPC患者死亡的25%。随着以阿比特龙为代表的新药可更加有效抑制雄激素信号通路，治疗去势抵抗性前列腺癌，NEPC患者比例很可能会进一步升高［5］。……