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利用不同的依赖性:如何识别和靶向雄激素受体阳性与四阴性乳腺癌。

Harnessing a Different Dependency: How to Identify and Target Androgen Receptor-Positive Versus Quadruple-Negative Breast Cancer.

机构信息

Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

出版信息

Horm Cancer. 2018 Apr;9(2):82-94. doi: 10.1007/s12672-017-0314-5. Epub 2018 Jan 16.

Abstract

The androgen receptor (AR) is a promising therapeutic target for a subset of triple-negative breast cancers (TNBCs) in which AR is expressed. However, the mechanistic action of AR and the degree to which primary and metastatic tumors depend on AR, both before and after conventional treatment, remain to be defined. We discuss preclinical and clinical data for AR+ TNBC, the difficulties in monitoring AR protein levels, new methods for determining AR status, the influence of AR on "stemness" in the context of TNBC, the role of combined inhibition of sex steroid production and AR, and the role of AR in regulation of the immune system. Although the exact role of AR in subsets of TNBC is still being characterized, new therapies that target AR and the production of androgens may provide additional options for patients with TNBC for whom chemotherapy is currently the sole treatment option.

摘要

雄激素受体(AR)是表达 AR 的三阴性乳腺癌(TNBC)亚组的有希望的治疗靶点。然而,AR 的机械作用以及在常规治疗之前和之后,原发和转移性肿瘤在多大程度上依赖 AR,仍有待确定。我们讨论了 AR+TNBC 的临床前和临床数据,监测 AR 蛋白水平的困难,确定 AR 状态的新方法,AR 在 TNBC 背景下对“干性”的影响,联合抑制性激素产生和 AR 的作用,以及 AR 在免疫系统调节中的作用。尽管 AR 在 TNBC 亚组中的确切作用仍在研究中,但针对 AR 和雄激素产生的新疗法可能为目前仅接受化疗的 TNBC 患者提供更多选择。

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