Assi Rita, Temraz Sally, Shamseddine Ali, Mukherji Deborah
Department of Internal Medicine, Division of Hematology Oncology American University of Beirut Medical Center Beirut, Lebanon.
Curr Drug Targets. 2016;17(3):290-302. doi: 10.2174/1389450116666150907101044.
The androgen receptor (AR) signalling pathway remains a key driver of prostate cancer progression despite castrate levels of testosterone in advanced disease. The androgen biosynthesis inhibitor abiraterone and the anti-androgen enzalutamide have been shown to prolong survival in randomized clinical trials both pre-and post-docetaxel chemotherapy and are now in routine clinical use. With the use of these drugs and other novel survival-prolonging therapeutics, patients with advanced prostate cancer are now living longer with better quality of life. This article will review pre-clinical and clinical data for AR-targeting therapeutics for advanced prostate cancer with a focus on mechanisms of resistance and future directions for research.
尽管晚期前列腺癌患者体内睾酮水平已处于去势水平,但雄激素受体(AR)信号通路仍是前列腺癌进展的关键驱动因素。雄激素生物合成抑制剂阿比特龙和抗雄激素药物恩杂鲁胺已在多西他赛化疗前后的随机临床试验中显示出可延长患者生存期,目前已在临床常规使用。随着这些药物及其他新型延长生存期疗法的应用,晚期前列腺癌患者现在的生存时间更长,生活质量也更高。本文将综述晚期前列腺癌AR靶向治疗的临床前和临床数据,重点关注耐药机制及未来研究方向。