Hackbart Hannah, Cui Xiaojiang, Lee Jin Sun
Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Department of Surgery, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Transl Breast Cancer Res. 2023 Oct 31;4. doi: 10.21037/tbcr-23-44. Epub 2023 Oct 23.
Breast cancer is a heterogeneous group of diseases characterized by diverse subtypes. Currently, the classification of breast cancer is based on the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). In addition to these receptors, the presence of the androgen receptor (AR) in breast cancer cells adds a layer of complexity to our understanding of the disease. The role of AR in breast cancer is intricate, as it can alter diverse signaling pathways in the presence of different hormone receptors (HRs). This complex interplay between signaling pathways affects patient outcomes and prognosis, and the presence of AR has a significant effect. While AR positivity is common in breast cancer, the efficacy of utilizing AR blockade as a monotherapy has been limited, demonstrating only modest results. To address this challenge, substantial efforts have been directed toward comprehending the intricacies of AR's role and pathways in breast cancer development in the hope of understanding its utility as a biomarker or drug target. Multiple ongoing clinical trials are currently investigating combination treatments involving AR inhibitors and other agents to disrupt oncogenic signaling pathways and their crosstalk. Particularly in the context of triple-negative breast cancer (TNBC), where targeted therapeutic options are lacking, extensive research efforts have been dedicated to exploring the potential of AR-related interventions. This review aims to provide an overview of the various breast cancer subtypes with AR signaling mechanisms, and ongoing clinical trials that hold the potential to reshape future clinical approaches.
乳腺癌是一组异质性疾病,具有多种不同的亚型。目前,乳腺癌的分类基于雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER2)的状态。除了这些受体外,乳腺癌细胞中雄激素受体(AR)的存在使我们对该疾病的理解更加复杂。AR在乳腺癌中的作用错综复杂,因为在存在不同激素受体(HRs)的情况下,它可以改变多种信号通路。信号通路之间的这种复杂相互作用会影响患者的治疗结果和预后,AR的存在具有显著影响。虽然AR阳性在乳腺癌中很常见,但将AR阻断作为单一疗法的疗效有限,仅显示出适度的效果。为应对这一挑战,人们已付出巨大努力来理解AR在乳腺癌发展中的作用和通路的复杂性,以期了解其作为生物标志物或药物靶点的效用。目前多项正在进行的临床试验正在研究涉及AR抑制剂和其他药物的联合治疗,以破坏致癌信号通路及其相互作用。特别是在缺乏靶向治疗选择的三阴性乳腺癌(TNBC)背景下,大量研究致力于探索AR相关干预措施的潜力。本综述旨在概述具有AR信号机制的各种乳腺癌亚型以及有望重塑未来临床治疗方法的正在进行的临床试验。