Risk of lung cancer and renin–angiotensin blockade: a concise review

Abstract

Purpose The blockade of the renin–angiotensin–aldosterone system (RAAS) by angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) is one of the most common treatments for hypertension, heart failure and renal diseases. However, concerns have been raised about a possible link between RAAS-blockers and an increased risk of cancer, particularly of lung cancer. This narrative review aims to give a critical appraisal of current evidence and to help physicians understand potential links between RAAS blockade and de novo lung cancer development. Methods Numerous pharmaco-epidemiologic studies, mostly retrospective cohort analyses, evaluated the association of RAAS blockade with lung cancer incidence and reported inconsistent findings. Meta-analyses could not further clarify a possible link between RAAS blockade and the risk of lung cancer. Results International regulatory agencies (FDA, EMA) have concluded that the use of RAAS blockers is not associated with an increased risk of developing lung cancer. Co-administration of RAAS blockers to systemic therapy of advanced non-small cell lung cancer seems to have positive effects on the outcome. Conclusion Until more comprehensive analyses have been completed, there is no need to change clinical practise. Additional prospective randomized trials with long-term follow-up are needed to investigate the effects of these drugs on the development and progression of lung cancer.

Regression of Lung Cancer in Mice by Intranasal Administration of SARS-CoV-2 Spike S1

“…Therefore, understanding molecular mechanisms and developing an effective therapeutic approach for lung cancer are of paramount importance. Interestingly, the renin-angiotensin system plays an important role in lung tumor progression or metastasis [ 4 ]. It has been shown that the low expression of angiotensin-converting enzyme 2 (ACE2) is associated with tumor grade in lung cancer and that upregulation of ACE2 suppresses the progression of non-small cell lung cancer (NSCLC) [ 5 , 6 ].…”

Effects of RAS inhibitors on all-site cancers and mortality in the Hong Kong diabetes surveillance database (2002-2019)

“…The differences in risk associations between ACEi and ARBs have been controversial. 46 , 47 In a post-hoc analysis of a RCT, 48 ACEi was associated with increased risk of lung cancer. However, in a nationwide retrospective cohort analysis of 70,000 community-dwelling adults in the United States, 49 ARBs were associated with reduced risk of lung cancer (HR=0.74, 0.67-0.83).…”

Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and cancer risk: an updated meta-analysis of observational studies

“…ARB has been reported to be associated with inhibition of AT1R, which activates cell migration, cell proliferation, inflammation, and angiogenesis in lung cancer. 21 On the other hand, ACEIs are known to induce lung accumulation of bradykinin and substance P, which promote tumour proliferation and angiogenesis). 22 Breast cancer is necessary to clarify cancer-specific biological plausibility.…”