Schweizer Michael T, Yu Evan Y
Division of Oncology, Department of Medicine, University of Washington, Seattle, WA 98109, USA.
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Cancers (Basel). 2017 Jan 11;9(1):7. doi: 10.3390/cancers9010007.
In the 1940s Charles Huggins reported remarkable palliative benefits following surgical castration in men with advanced prostate cancer, and since then the androgen receptor (AR) has remained the main therapeutic target in this disease. Over the past couple of decades, our understanding of AR-signaling biology has dramatically improved, and it has become apparent that the AR can modulate a number of other well-described oncogenic signaling pathways. Not surprisingly, mounting preclinical and epidemiologic data now supports a role for AR-signaling in promoting the growth and progression of several cancers other than prostate, and early phase clinical trials have documented preliminary signs of efficacy when AR-signaling inhibitors are used in several of these malignancies. In this article, we provide an overview of the evidence supporting the use of AR-directed therapies in prostate as well as other cancers, with an emphasis on the rationale for targeting AR-signaling across tumor types.
20世纪40年代，查尔斯·哈金斯报告称，对晚期前列腺癌男性患者进行手术去势后有显著的姑息治疗效果，从那时起，雄激素受体（AR）一直是这种疾病的主要治疗靶点。在过去几十年里，我们对AR信号生物学的理解有了显著提高，并且已经很明显，AR可以调节许多其他已充分描述的致癌信号通路。毫不奇怪，越来越多的临床前和流行病学数据现在支持AR信号在促进除前列腺癌之外的几种癌症的生长和进展中发挥作用，并且早期临床试验已经证明，在其中几种恶性肿瘤中使用AR信号抑制剂时有初步的疗效迹象。在本文中，我们概述了支持在前列腺癌以及其他癌症中使用AR导向疗法的证据，重点是针对不同肿瘤类型靶向AR信号的基本原理。
