Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan.
J Cell Physiol. 2014 Mar;229(3):271-6. doi: 10.1002/jcp.24456.
Prostate cancer (PCa) is the second leading cause of cancer death in men. Current research findings suggest that the androgen receptor (AR) and its signaling pathway contribute significantly to the progression of metastatic PCa. The AR is a ligand activated transcription factor, where androgens such as testosterone (T) and dihydroxytestosterone (DHT) act as the activating ligands. However in many metastatic PCa, the AR functions promiscuously and is constitutively active through multiple mechanisms. Inhibition of enzymes that take part in androgen synthesis or synthesizing antiandrogens that can inhibit the AR are two popular methods of impeding the androgen receptor signaling axis; however, the inhibition of androgen-independent activated AR function has not yet been fully exploited. This article focuses on the development of emerging novel agents that act at different steps along the androgen-AR signaling pathway to help improve the poor prognosis of PCa patients.
前列腺癌（PCa）是男性癌症死亡的第二大主要原因。目前的研究结果表明，雄激素受体（AR）及其信号通路对转移性 PCa 的进展有重要贡献。AR 是一种配体激活的转录因子，其中雄激素如睾酮（T）和二氢睾酮（DHT）作为激活配体。然而，在许多转移性 PCa 中，AR 表现出混杂的功能，并通过多种机制持续激活。抑制参与雄激素合成的酶或合成可抑制 AR 的抗雄激素是阻碍雄激素受体信号轴的两种常用方法；然而，雄激素非依赖性激活的 AR 功能的抑制尚未得到充分利用。本文重点介绍了沿着雄激素-AR 信号通路的不同步骤作用的新型药物的开发，以帮助改善 PCa 患者的不良预后。
