The renin–angiotensin system and cancer: old dog, new tricks

• Published in: Nature reviews. Cancer Vol. 10; no. 11; pp. 745 - 759
• Main Authors: Thomas, Walter G, Hannan, Ross D, George, Amee J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2010; Nature Publishing Group
• Subjects: 631/67/1059/602; 631/80/304; Biomedical and Life Sciences; Biomedicine; Cancer Research; Colorectal cancer; Development and progression; Genetic aspects; Humans; Neoplasms - physiopathology; Physiological aspects; Renin-angiotensin system; Renin-Angiotensin System - drug effects; review-article; Australia
• ISSN: 1474-175X; 1474-1768
• DOI: 10.1038/nrc2945

Key Points This Review presents a contemporary update of the renin–angiotensin system (RAS), explaining its links to cancer through tissue remodelling, inflammation, angiogenesis and apoptosis. In vitro , animal and clinical studies indicate that the RAS is frequently dysregulated in malignancy and correlates with poor patient outcomes. Antagonism of the RAS mostly suppresses tumour growth, metastasis and angiogenesis in a broad range of experimental models of malignancy. Retrospective studies in humans provide some evidence that long-term use of angiotensin-converting enzyme inhibitors might modulate cancer growth and progression. The potential for retooling current drugs that target the RAS for application to cancer therapy is discussed. This Review describes the evidence linking the renin–angiotensin system (RAS) to cancer, through its roles in processes such as apoptosis, angiogenesis and tissue remodelling. Could RAS inhibitors currently used in the clinic be retooled to treat cancer? For cancers to develop, sustain and spread, the appropriation of key homeostatic physiological systems that influence cell growth, migration and death, as well as inflammation and the expansion of vascular networks are required. There is accumulating molecular and in vivo evidence to indicate that the expression and actions of the renin–angiotensin system (RAS) influence malignancy and also predict that RAS inhibitors, which are currently used to treat hypertension and cardiovascular disease, might augment cancer therapies. To appreciate this potential hegemony of the RAS in cancer, an expanded comprehension of the cellular actions of this system is needed, as well as a greater focus on translational and in vivo research.