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.

Keywords: Angiotensin enzyme inhibitors; Angiotensin receptor blockers; Non-small cell lung cancer; Renin–angiotensin–aldosterone system.

Fig. 1

Simplified scheme of the RAAS cascade and signal transduction pathways in carcinogenesis. ACEI angiotensin converting enzyme inhibitor, ACE angiotensin converting enzyme, ACE2 angiotensin converting enzyme-2, ARBs angiotensin receptor blockers, AT1R angiotensin-II-receptor type 1, AT2R angiotensin-II-receptor type 2, MasR Mas receptor, EGFR epidermal growth factor receptor, NADPH-Ox nicotinamide adenine dinucleotide phosphate oxidase, ROS reactive oxygen species, TGF-beta transforming growth factor beta, PI3K phosphoinositide 3-kinase, MAPK/ERK mitogen-activated protein kinase/extracellular signal-regulated kinase, JAK Janus kinase, STAT signal transducer and activator of transcription, PKC protein kinase C, RAS rat sarcoma protein, PLZF promyelocytic leukemia zink finger protein, ATBP AT2R binding protein, SHP-1 Src homology region 2 domain-containing phosphatase-1, PLA-2 phospholipase 2, NOS nitric oxide synthase