Department of Urology and Cancer Center, University of California Davis Medical Center, 4645 2nd Ave, Research III, Suite 1300, Sacramento, CA 95817, USA.
World J Urol. 2012 Jun;30(3):287-95. doi: 10.1007/s00345-011-0771-3. Epub 2011 Oct 19.
The emergence of castration resistance has remained the primary obstacle in prostate cancer therapy for several decades. Mechanisms likely to be involved in castration-resistant progression have been studied extensively, but have failed to yield many meaningful and effective targets. The re-activation of the androgen receptor (AR) in castration-resistant prostate cancer (CRPC) is now recognized as the central event in this process, and therapeutic modalities are being devised to combat it.
A review of literature was performed to highlight the important factors that play a role in the aberrant activation of the AR in CRPC.
Seminal and exciting advances made in the past few years in the discovery of the roles of new intrinsic factors such as intracrine androgens, gene fusions involving the ETS oncogenes, and splice variants of the AR are reviewed. New and emerging hypotheses about the involvement of factors such as cytokines and other signaling pathways are discussed.
This review summarizes the most recent advances in the persistent activation of the androgen receptor signaling pathway and provides a perspective about their significance in CRPC progression.
几十年来，去势抵抗的出现一直是前列腺癌治疗的主要障碍。已经广泛研究了可能涉及去势抵抗进展的机制，但未能产生许多有意义和有效的靶点。在去势抵抗性前列腺癌（CRPC）中，雄激素受体（AR）的重新激活现在被认为是这个过程中的核心事件，并且正在设计治疗方法来对抗它。
对文献进行了回顾，以强调在 CRPC 中 AR 异常激活中起作用的重要因素。
回顾了过去几年在发现新的内在因素（如细胞内雄激素）、涉及 ETS 癌基因的基因融合以及 AR 剪接变体的作用方面取得的重要进展。还讨论了关于细胞因子和其他信号通路等因素参与的新出现的假设。
本综述总结了雄激素受体信号通路持续激活的最新进展，并提供了它们在 CRPC 进展中的意义的观点。
