Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.
Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China; Department of Medical Oncology, Jinling Clinical College, Nanjing Medical University, Nanjing, 210002, China.
Biochim Biophys Acta Rev Cancer. 2018 Dec;1870(2):283-290. doi: 10.1016/j.bbcan.2018.05.004. Epub 2018 May 25.
Androgen receptor (AR) targeted treatment has shown promising preliminary results in triple negative breast cancer (TNBC). Identification of AR-associated signaling pathways is of great significance for in-depth understanding of their roles in pathogenesis of TNBC. To meet this objective, preclinical and clinical studies were conducted to clarify the biological interactions of AR signaling and combination strategies based on AR-targeted therapy. Biologically, AR signaling in TNBC which not only interacts with a network of key pathways, involving PI3K/AKT/mTOR, cell cycle, and DNA damage repair pathways, but mediates pivotal processes of tumor initiation and immunogenic modulation, may present an opportunity to overcome the insensitivity of single AR-targeted therapy. Research in investigating androgen-blockade based combination therapy in this aggressive tumor has demonstrated promising benefit in preclinical studies, and comparable clinical trials of combined strategies with CDK4/6 inhibitors, PI3K inhibition, chemotherapy, and immunotherapy, are ongoing. Accordingly, clinical interpretation of AR-related biological interactions, aiming at combined blockade of the signaling pathways may pave a new way for endocrine-based therapy in the treatment of TNBC.
雄激素受体 (AR) 靶向治疗在三阴性乳腺癌 (TNBC) 中显示出有希望的初步结果。鉴定 AR 相关信号通路对于深入了解它们在 TNBC 发病机制中的作用具有重要意义。为了实现这一目标，进行了临床前和临床研究，以阐明 AR 信号转导的生物学相互作用以及基于 AR 靶向治疗的联合策略。从生物学角度来看，TNBC 中的 AR 信号转导不仅与涉及 PI3K/AKT/mTOR、细胞周期和 DNA 损伤修复途径的关键途径网络相互作用，还介导肿瘤起始和免疫调节的关键过程，这为克服单一 AR 靶向治疗的不敏感性提供了机会。在这种侵袭性肿瘤中研究基于雄激素阻断的联合治疗的研究表明，在临床前研究中具有良好的获益，目前正在进行联合策略与 CDK4/6 抑制剂、PI3K 抑制、化疗和免疫治疗的比较临床试验。因此，针对信号通路的联合阻断的 AR 相关生物学相互作用的临床解释可能为基于内分泌治疗的 TNBC 治疗开辟新途径。
