The renin-angiotensin-aldosterone system (RAAS) is a hormone system that plays a crucial role in regulating blood pressure and body fluid balance. It is also involved in the development of various health conditions such as hypertension, heart failure, cardiovascular diseases, and renal diseases (Fountain, Kaur, & Lappin, 2023). Recent research has expanded our understanding of the RAAS, revealing a more intricate and multifaceted system with far-reaching implications in both normal physiology and disease processes. Notably, there is growing interest in exploring the connection between the RAAS and cancer biology (Hassani, Attar, & Firouzabadi, 2023).

In recent years, there has been a growing interest in studying the role of the RAAS in cancer. This interest is driven by the observation of dysregulation of the RAAS in various types of cancer and the promising results of using RAAS modulators to target cancer in both experimental models and patients. It has been found that patients treated with renin-angiotensin system inhibitor (RASi) have a lower risk of developing certain cancers, suggesting that the specific antagonism of the RAAS, rather than their anti-hypertensive effects, is responsible for this protective effect (Pinter & Jain, 2017). Furthermore, a localized “paracrine” RAAS mechanism has been identified in many types of cancer, and disruption of the normal regulation of the RAAS is believed to underlie its involvement in cancer development (Almutlaq, Alamro, Alamri, Alghamdi, & Barhoumi, 2021a).

In light of these emerging data, we discussed the role of the RAAS in cancer biology and tumor immunity in this chapter. In addition, by carefully analyzing the studies, we identified the diagnostic and prognostic potentials of RAAS genetic variants, as well as their therapeutic potential, which makes a case for targeting RAAS to improve the treatment of primary and metastatic tumors.