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Paving the path ForwARd: Advances and challenges in androgen receptor targeting in breast cancer
Nithya Sridhar1, Toshiaki Iwase2, Xuemei Xie3
1Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA.
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.
Insights
Androgen receptors (AR) are key in breast cancer research. Understanding AR
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Androgen receptors (AR) are expressed in 60-90% of breast cancers.
- AR-targeted therapy is standard for prostate cancer but not established for breast cancer.
- AR's role in breast cancer subtypes and its potential as a therapeutic target require further investigation.
Purpose of the Study:
- To review the clinical perspective of AR in breast cancer.
- To discuss AR biology, its role as a biomarker, and AR-targeted therapy development.
- To emphasize the distinct roles of AR in ER-positive and ER-negative breast cancer subtypes.
Main Methods:
- Literature review focusing on AR biology, biomarker potential, and therapeutic strategies.
- Analysis of AR's distinct roles in estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast cancer.
- Discussion of challenges and potential solutions for AR-targeted therapy development in breast cancer.
Main Results:
- AR plays a significant role in breast cancer, with potential for targeted therapies.
- AR's function and impact differ across breast cancer subtypes (ER+ vs. ER-).
- Current understanding and standardized thresholds for AR expression limit clinical application.
Conclusions:
- AR-targeted therapies show promise but require a deeper understanding of AR's role in different breast cancer subtypes.
- Biomarker-driven strategies and standardized AR expression thresholds are crucial for optimizing patient selection and treatment.
- Overcoming current hurdles is essential for establishing a robust clinical landscape for AR-targeted therapies in breast cancer.
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