Androgen-deprivation therapy-induced aggressive prostate cancer with neuroendocrine differentiation

作     者：Julia Lipianskaya Alexa Cohen Clark J Chen Elaine Hsia Jill Squires Zhen Li Yaqun Zhang Wei Li Xufeng Chen Hua Xu Jiaoti Huang 

作者机构：Departments of Pathology and Urology Jonsson Comprehensive Cancer Center and Broad Center of Regenerative Medicine and Stem Cell Research David Geffen School of Medicine at UCLA Los Angeles CA USA. 

出 版 物：《Asian Journal of Andrology》 (亚洲男性学杂志（英文版）)

年 卷 期：2014年第16卷第4期

页      面：541-544页

核心收录：

学科分类：0710[理学-生物学] 090502[农学-动物营养与饲料科学] 071010[理学-生物化学与分子生物学] 1002[医学-临床医学] 081704[工学-应用化学] 07[理学] 0905[农学-畜牧学] 08[工学] 0817[工学-化学工程与技术] 09[农学] 

主　　题：neuroendocrine prostate cancer small cell carcinoma therapy 

摘      要：Most prostate cancers （PCas） are classified as acinar type （conventional） adenocarcinoma which are composed of tumor cells with luminal differentiation including the expression of androgen receptor （AR） and prostate-specific antigen （PSA）. There are also scattered neuroendocrine （NE） cells in every case of adenocarcinoma. The NE cells are quiesecent, do not express AR or PSA, and their function remains unclear. We have demonstrated that IL8-CXCR2-P53 pathway provides a growth-inhibitory signal and keeps the NE cells in benign prostate and adenocarcinoma quiescent. Interestingly, some patients with a history of adenocarcinoma recur with small cell neuroendocrine carcinoma （SCNC） after hormonal therapy, and such tumors are composed of pure NE cells that are highly proliferative and aggressive, due to P53 mutation and inactivation of the IL8-CXCR2-P53 pathway. The incidence of SCNC will likely increase due to the widespread use of novel drugs that further inhibit AR function or intratumoral androgen synthesis. A phase II trial has demonstrated that platinum-based chemotherapy may be useful for such therapy-induced tumors.