The renin-angiotensin system (RAS) is a network of proteins regulating many aspects of human physiology, including cardiovascular, pulmonary, and immune system physiology. The RAS is a complicated network of G-protein coupled receptors (GPCRs) (i.e., AT1R, AT2R, MASR, and MRGD) orchestrating the effects of several hormones (i.e., angiotensin II, angiotensin (1–7), and alamandine) produced by protease-based transmembrane receptors (ACE1 and ACE2). Two signaling axes have been identified in the RAS endocrine system that mediate the proliferative actions of angiotensin II (i.e., the AT1R-based pathway) or the anti-proliferative effects of RAS hormones (i.e., the AT2R-, MAS-, and MRGD-based pathways). Disruption of the balance between these two axes can cause different diseases (e.g., cardiovascular pathologies and the severe acute respiratory syndrome coronavirus 2- (SARS-CoV-2)-based COVID-19 disease). It is now accepted that all the components of the RAS endocrine system are expressed in cancer, including cancer of the breast. Breast cancer (BC) is a multifactorial pathology for which there is a continuous need to identify novel drugs. Here, I reviewed the possible roles of both axes of the RAS endocrine network as potential druggable pathways in BC. Remarkably, the analysis of the current knowledge of the different GPCRs of the RAS molecular system not only confirms that AT1R could be considered a drug target and that its inhibition by losartan and candesartan could be useful in the treatment of BC, but also identifies Mas-related GPCR member D (MRGD) as a druggable protein. Overall, the RAS of GPCRs offers multifaceted opportunities for the development of additional compounds for the treatment of BC.

中文翻译：

---

乳腺癌血管紧张素受体网络。

肾素-血管紧张素系统（RAS）是一种蛋白质网络，可调节人体生理的许多方面，包括心血管，肺和免疫系统的生理。RAS是由G蛋白偶联受体（GPCR）（即AT1R，AT2R，MASR和MRGD）组成的复杂网络，可协调产生的几种激素（即血管紧张素II，血管紧张素（1-7）和阿拉曼定）的作用通过基于蛋白酶的跨膜受体（ACE1和ACE2）。在RAS内分泌系统中已经确定了两个信号转导轴，它们介导了血管紧张素II的增殖作用（即基于AT1R的途径）或RAS激素的抗增殖作用（即AT2R-，MAS-和MRGD-基础途径）。破坏这两个轴之间的平衡会导致不同的疾病（例如，心血管疾病和严重的急性呼吸系统综合症冠状病毒2（SARS-CoV-2）为基础的COVID-19疾病）。现在已经公认，RAS内分泌系统的所有组成部分都在癌症中表达，包括乳腺癌。乳腺癌（BC）是一种多因素病理，因此不断需要鉴定新药。在这里，我回顾了RAS内分泌网络的两个轴作为BC中潜在药物通路的可能作用。值得注意的是，对RAS分子系统不同GPCR的当前知识进行的分析不仅证实AT1R可以被视为药物靶标，而且氯沙坦和坎地沙坦对AT1R的抑制作用可用于治疗BC，而且还可以确定Mas-相关的GPCR成员D（MRGD）作为药物蛋白。总体，