Cancer stem cells (CSCs) drive metastasis, treatment resistance, and tumor recurrence. CSCs reside within a niche, an anatomically distinct site within the tumor microenvironment (TME) that consists of malignant and non-malignant cells, including immune cells. The renin–angiotensin system (RAS), a critical regulator of stem cells and key developmental processes, plays a vital role in the TME. Non-malignant cells within the CSC niche and stem cell signaling pathways such as the Wnt, Hedgehog, and Notch pathways influence CSCs. Components of the RAS and cathepsins B and D that constitute bypass loops of the RAS are expressed on CSCs in many cancer types. There is extensive in vitro and in vivo evidence showing that RAS inhibition reduces tumor growth, cell proliferation, invasion, and metastasis. However, there is inconsistent epidemiological data on the effect of RAS inhibitors on cancer incidence and survival outcomes, attributed to different patient characteristics and methodologies used between studies. Further mechanistic studies are warranted to investigate the precise effects of the RAS on CSCs directly and/or the CSC niche. Targeting the RAS, its bypass loops, and convergent signaling pathways participating in the TME and other key stem cell pathways that regulate CSCs may be a novel approach to cancer treatment:

癌症干细胞 (CSC) 驱动转移、治疗抵抗和肿瘤复发。CSC 存在于一个生态位中，这是肿瘤微环境 (TME) 中解剖学上不同的部位，由恶性和非恶性细胞（包括免疫细胞）组成。肾素-血管紧张素系统 (RAS) 是干细胞和关键发育过程的关键调节剂，在 TME 中起着至关重要的作用。CSC壁龛内的非恶性细胞干细胞信号通路如 Wnt、Hedgehog 和 Notch 通路影响 CSC。构成 RAS 旁路环的 RAS 组分和组织蛋白酶 B 和 D 在许多癌症类型的 CSC 上表达。大量的体外和体内证据表明，RAS 抑制可减少肿瘤生长、细胞增殖、侵袭和转移。然而，由于不同的患者特征和研究之间使用的方法不同，关于 RAS 抑制剂对癌症发病率和生存结果的影响的流行病学数据不一致。需要进一步的机制研究来研究 RAS 对 CSC 和/或 CSC生态位的精确影响. 靶向 RAS、其旁路回路和参与 TME 和其他调节 CSC 的关键干细胞通路的会聚信号通路可能是一种新的癌症治疗方法：