Grist Emily, de Bono Johann S, Attard Gerhardt
Institute of Cancer Research, Cancer Therapeutics, 15 Cotswold Rd, Sutton, Surrey SM25NG, UK; Royal Marsden NHS Foundation Trust, London, UK.
Institute of Cancer Research, Cancer Therapeutics, 15 Cotswold Rd, Sutton, Surrey SM25NG, UK; Royal Marsden NHS Foundation Trust, London, UK.
J Steroid Biochem Mol Biol. 2015 Jan;145:157-63. doi: 10.1016/j.jsbmb.2014.09.006. Epub 2014 Sep 22.
Metastatic castration resistant prostate cancer (CRPC) is associated with a rise in PSA, suggesting an increase in transcription of steroid receptor regulated genes. The efficacy of the new anti-androgen therapies abiraterone and enzalutamide, that target extra-gonadal activation of androgen signaling, confirm CRPC's addiction to genes regulated by the androgen receptor (AR). However, patients invariably progress and develop resistance. This review focuses on mechanisms of drug resistance associated with the AR and steroidogenesis in CRPC. Understanding this persistent dependency and adaptation to the androgen axis in CRPC will lead to an understanding of resistance to new licensed therapies and to novel drug discovery, ultimately improving clinical outcome in CRPC. This article is part of a Special Issue entitled 'Essential role of DHEA'.
转移性去势抵抗性前列腺癌（CRPC）与前列腺特异性抗原（PSA）升高相关，提示类固醇受体调节基因的转录增加。新型抗雄激素疗法阿比特龙和恩杂鲁胺靶向雄激素信号的性腺外激活，其疗效证实了CRPC对雄激素受体（AR）调节基因的依赖性。然而，患者最终总会病情进展并产生耐药性。本综述聚焦于CRPC中与AR和类固醇生成相关的耐药机制。了解CRPC中对雄激素轴的这种持续依赖性和适应性，将有助于理解对新获批疗法的耐药性以及发现新药物，最终改善CRPC的临床结局。本文是名为“脱氢表雄酮的重要作用”特刊的一部分。
