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

Nature Reviews Cancer volume 10, pages 745–759 (2010)Cite this article

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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.

Abstract

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.

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Figure 1: RAS receptor signalling pathways.
Figure 2: Contribution of stromal cell RAS signalling to tumour inflammation, angiogenesis and growth.
Figure 3: RAS and apoptosis.

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Acknowledgements

The authors apologise to those authors whose work is not cited because of space limitations. R.D.H. and W.G.T. are funded through Grants and Fellowships from the National Health and Medical Research Council of Australia, Cancer Council of Victoria, and the Victorian Breast Cancer Consortium, Australia.

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  1. Walter G. Thomas and Ross D. Hannan: These authors contributed equally to this work.

Authors and Affiliations

  1. School of Biomedical Sciences, The University of Queensland, St. Lucia, 4072, Queensland, Australia

    Amee J. George & Walter G. Thomas

  2. Research Division, Growth Control and Differentiation Program, Peter MacCallum Cancer Centre, East Melbourne, 3002, Victoria, Australia

    Amee J. George & Ross D. Hannan

  3. Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, 3010, Victoria, Australia

    Ross D. Hannan

  4. Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3800, Victoria, Australia

    Ross D. Hannan

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Supplementary information

Supplementary information S1 (table)

Examples of RAS component expression in human cancer tissues and cell lines (PDF 242 kb)

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DATABASES

ClinicalTrials.gov 

NCT00471562

National Cancer Institute Drug Dictionary 

candesartan

captopril

lisinopril

perindopril

NCBI SNP database 

snprs5186

rs1799752

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George, A., Thomas, W. & Hannan, R. The renin–angiotensin system and cancer: old dog, new tricks. Nat Rev Cancer 10, 745–759 (2010). https://doi.org/10.1038/nrc2945

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