Division of Cancer Therapeutics, Signal Transduction & Molecular Pharmacology and Clinical Pharmacology & Trials Team, Institute of Cancer Research, Sutton, SM25NG, United Kingdom.
Annu Rev Med. 2013;64:1-13. doi: 10.1146/annurev-med-121211-091605. Epub 2012 Sep 27.
Suppression of gonadal androgens by medical or surgical castration remains the mainstay of treatment for patients with advanced prostate cancer. However, the response to treatment is not durable, and transition to a "castration-resistant" state is invariable. Recent advances in our understanding of the androgen receptor signaling pathway have led to the development of therapeutic strategies to overcome castration resistance. This article reviews current concepts and challenges behind targeting continued androgen receptor signaling in castration-resistant prostate cancer and provides an overview of recently completed and ongoing clinical trials of novel hormonal agents, with a focus on abiraterone acetate and enzalutamide (MDV3100).
通过医学或手术去势来抑制性腺雄激素仍然是治疗晚期前列腺癌患者的主要方法。然而,治疗的效果并不持久,向“去势抵抗”状态的转变是不可避免的。最近,我们对雄激素受体信号通路的理解有了进展,这使得我们能够制定出治疗策略来克服去势抵抗。本文综述了目前针对去势抵抗性前列腺癌中持续的雄激素受体信号的靶向治疗的概念和挑战,并概述了最近完成和正在进行的新型激素药物的临床试验,重点介绍阿比特龙和恩杂鲁胺(MDV3100)。