The angiotensin II type 1 receptor in cancer

The renin-angiotensin system is a key regulator of blood pressure homeostasis, with its primary effector, the angiotensin II type 1 receptor (AT1R), mediating vasoconstriction and processes fundamental to cancer progression including proliferation, angiogenesis, and metastasis.  Elevated AT1R expression is consistently linked to poor prognosis and therapeutic resistance across various malignancies and preclinical studies provide compelling evidence that AT1R activation drives key cancer related processes, while its inhibition by angiotensin receptor blockers suppresses tumour growth, induces apoptosis, reduces angiogenesis, and inhibits metastasis across a wide range of cancer models.  Critically, angiotensin receptor blockers effectively modulate the tumour microenvironment, alleviating fibrosis, promoting anti-tumour immune cell phenotypes, and enhancing the efficacy of targeted therapies, chemotherapies, and immunotherapies. 

A recent review by Butcher et al seeks to summarise the current understanding of AT1R’s role in cancer, highlight preclinical and clinical investigations of targeting the renin-angiotensin system, and suggest further strategies to unlock its potential.  Realising the full therapeutic promise of AT1R targeting in oncology requires a multifaceted approach, including the development of innovative delivery systems, such as tumour microenvironment activated ARBs, and the exploration of advanced therapeutic modalities such as antibody based AT1R inhibitors. 

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