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开辟前进道路:乳腺癌雄激素受体靶向治疗的进展与挑战

Paving the path ForwARd: Advances and challenges in androgen receptor targeting in breast cancer.

作者信息

Sridhar Nithya, Iwase Toshiaki, Xie Xuemei, Lee Jangsoon, Damodaran Senthil, Ueno Naoto T

机构信息

Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA.

Translational and Clinical Research Program, University of Hawai'i Cancer Center, Honolulu, HI, USA.

出版信息

Cancer Treat Rev. 2025 Jul;138:102958. doi: 10.1016/j.ctrv.2025.102958. Epub 2025 May 15.

Abstract

The role of androgen receptors (AR) in breast cancer is crucial for preclinical and clinical research. While AR-targeted therapy is a standard treatment for prostate cancer, the application of this therapeutic strategy to breast cancer has not been established. Indeed, AR is expressed in around 60-90% of breast cancers, making it imperative that we learn more about its prognostic and predictive impacts and targeting potential in breast cancer. Over the past decade, AR-targeted therapies ─ including AR antagonists and selective AR modulators ─ have shown promise in breast cancer treatment. However, an incomplete understanding of AR's role across breast cancer subtypes hinders clinical application. The lack of standardized AR expression thresholds further complicates patient selection, underscoring the urgent need for biomarker-driven strategies to optimize AR-targeted approaches in breast cancer. In this review, we provide an overview of a clinical perspective of AR in breast cancer by discussing AR biology, AR as a biomarker, and AR-targeted therapy development. We present our review with a particular emphasis on the distinct roles of AR in ER-positive (ER+) and ER-negative (ER-) breast cancer subtypes. Finally, the paper addresses the hurdles that have impeded the development of a robust clinical landscape for AR-targeted therapies and possible solutions for overcoming these challenges.

摘要

雄激素受体(AR)在乳腺癌中的作用对于临床前和临床研究至关重要。虽然AR靶向治疗是前列腺癌的标准治疗方法,但这种治疗策略在乳腺癌中的应用尚未确立。事实上,约60%-90%的乳腺癌中表达AR,这使得我们必须更多地了解其在乳腺癌中的预后和预测影响以及靶向潜力。在过去十年中,AR靶向治疗——包括AR拮抗剂和选择性AR调节剂——在乳腺癌治疗中显示出前景。然而,对AR在不同乳腺癌亚型中的作用理解不全面阻碍了临床应用。缺乏标准化的AR表达阈值进一步使患者选择复杂化,凸显了迫切需要基于生物标志物的策略来优化乳腺癌中AR靶向方法。在本综述中,我们通过讨论AR生物学、AR作为生物标志物以及AR靶向治疗的发展,概述了AR在乳腺癌中的临床视角。我们的综述特别强调了AR在雌激素受体阳性(ER+)和雌激素受体阴性(ER-)乳腺癌亚型中的不同作用。最后,本文探讨了阻碍AR靶向治疗稳健临床格局发展的障碍以及克服这些挑战可能的解决方案。

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