Culig Zoran
Innsbruck Medical University, Experimental Urology, Department of Urology , Anichstrasse 35, A-6020 Innsbruck , Austria +43 512 504 24717 ; +43 512 504 24817 ;
Expert Opin Pharmacother. 2014 Jul;15(10):1427-37. doi: 10.1517/14656566.2014.915313. Epub 2014 Jun 2.
The androgen receptor (AR) is a ligand-activated transcription factor that is expressed in primary and metastatic prostate cancers. There are advances in endocrine therapy for prostate cancer that are based on improved understanding of AR function.
PubMed has been used to include most important publications on targeting the AR in prostate cancer. AR expression may be downregulated by agents used for chemoprevention of prostate cancer or, in models of advanced prostate cancer, by antisense oligonucleotides. New drugs that inhibit the steroidogenic enzyme CYP17A1 (abiraterone acetate) or diminish nuclear translocation of the AR (enzalutamide) have been shown to improve patients' survival in prostate cancer. However, it is clear that there is a development of resistance to these novel therapies. They may include increased expression of truncated, constitutively active AR or activation of the signaling pathway of signal transducers and activators of transcription.
Although introduction of novel drugs have improved patients' survival, there is a need to investigate the mechanisms of resistance further. The role of truncated AR and compensatory activation of signaling pathways as well as the development of scientifically justified combination therapies seems to be issues of a high priority.
雄激素受体（AR）是一种配体激活的转录因子，在原发性和转移性前列腺癌中均有表达。基于对AR功能的深入了解，前列腺癌的内分泌治疗取得了进展。
已利用PubMed纳入了关于前列腺癌中靶向AR的最重要出版物。用于前列腺癌化学预防的药物或在晚期前列腺癌模型中，反义寡核苷酸可能会下调AR表达。已证明抑制类固醇生成酶CYP17A1的新药（醋酸阿比特龙）或减少AR核转位的药物（恩杂鲁胺）可改善前列腺癌患者的生存率。然而，显然这些新型疗法会产生耐药性。耐药机制可能包括截短的、组成型活性AR的表达增加或信号转导和转录激活因子信号通路的激活。
尽管新型药物的引入提高了患者的生存率，但仍需要进一步研究耐药机制。截短的AR的作用、信号通路的代偿性激活以及科学合理的联合疗法的开发似乎是高度优先考虑的问题。
