Do renin–angiotensin system inhibitors influence the recurrence, metastasis, and survival in cancer patients?

Sun, Hong; Li, Tao; Zhuang, Rongyuan; Cai, Weimin; Zheng, Yuanting

doi:10.1097/md.0000000000006394

Cited by 67 publications

(55 citation statements)

References 85 publications

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“…It is exciting to speculate that CSCs may be a novel therapeutic target by modulation of the RAS using existing medications such as aliskiren which targets renin, β-blockers which inhibit the production of prorenin and hence decrease renin levels, ACE inhibitors and ATII receptor blockers [36][37][38] . A recent metaanalysis on the use of ACE inhibitors and ATIIR1 blockers demonstrate an average 20% improved survival or reduction of recurrence in different types of cancers, including primary CRC [29] , suggesting a crucial role of these drugs in tumorigenesis, potentially through modulation on the RAS, although this requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

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Cancer stem cells in liver metastasis from colon adenocarcinoma express components of the renin-angiotensin system

Narayanan¹,

Wickremesekera²,

Schaijik³

et al. 2019

JCMT

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Aim: We have recently identified a cancer stem cell (CSC) subpopulations within the tumor nests (TNs) and another within the peritumoral stroma (PTS) in liver metastasis from colon adenocarcinoma (LMCA). This study investigated the expression of components of the renin-angiotensin (RAS): pro-renin receptor (PRR), angiotensin converting enzyme (ACE), and angiotensin II receptor 1 (ATIIR1) and angiotensin II receptor 2 (ATIIR2) in LMCA. Methods: 3,3-Diaminobenzidine (DAB) immunohistochemical (IHC) staining was performed on 16 LMCA samples for PRR, ACE, ATIIR1 and ATIIR2. Immunofluorescence (IF) IHC staining was performed to investigate co-expression of these components of the RAS with SOX2 or OCT4. NanoString analysis (n = 6) and Western blotting (WB, n = 3) were performed on snap-frozen LMCA samples to confirm mRNA and protein expression, respectively. Results: DAB IHC staining showed the expression of PRR, ACE, ATIIR1 and ATIIR2 within all LMCA samples. NanoString analysis and WB confirmed gene and protein expression of these components of the RAS. IF IHC staining demonstrated expression of PRR, ATIIR1 and ATIIR2 by the SOX2 + CSCs within the TNs and the OCT4 + CSCs within the PTS. ACE was expressed on the endothelium of the microvessels within the PTS. Conclusion: These finding suggests the CSCs within LMCA maybe a novel therapeutic target by manipulation of the RAS.

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Section: Discussionmentioning

confidence: 99%

“…Hence CSCs may be a novel therapeutic target by modulation of the RAS. A recent meta-analysis reports an average 20% reduced risk of metastasis and improved survival from cancer including CRC, in patients who are administered RAS modulators [29] .…”

Section: Introductionmentioning

confidence: 99%

Cancer stem cells in liver metastasis from colon adenocarcinoma express components of the renin-angiotensin system

Narayanan¹,

Wickremesekera²,

Schaijik³

et al. 2019

JCMT

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“…hepatocellular carcinoma, upper-tract urothelial carcinoma, and bladder cancer compared with patients without RAS inhibitor treatment (7). There was also a trend toward better outcome for patients with lung cancer and melanoma treated with RAS inhibitors.…”

Section: Funding Nihmentioning

confidence: 91%

“…RAS components are also present in different cancer types and may enhance survival, proliferation, and metastasis of tumor cells (4,5). Treatment with ACE inhibitors (ACEIs) is associated with a decreased risk of developing certain cancers (6,7), and slows pulmonary function decline in patients with pulmonary diseases (8).…”

Section: Introductionmentioning

confidence: 99%

“…Risk of developing cancer is significantly lower in patients receiving ACEIs compared with controls or to patients receiving other antihypertensive drugs (6,7). A meta-analysis of 55 studies examining the relationship between overall survival and RAS inhibition concluded that significant improvement in survival was seen in RAS-inhibitor-treated patients with renal cell carcinoma, gastric cancer, pancreatic cancer,…”

Section: Introductionmentioning

confidence: 99%

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Angiotensin-converting enzyme inhibitors may affect pulmonary function in lymphangioleiomyomatosis

et al. 2019

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Exploring the causal relationship between antihypertensive drugs and glioblastoma by combining drug target Mendelian randomization study, eQTL colocalization, and single‐cell RNA sequencing

Zhao,

Xie,

Ding

et al. 2024

Environmental Toxicology

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Recent reports indicate a potential oncogenic role of antihypertensive drugs in common cancers. However, it remains uncertain whether this phenomenon influences the risk of glioblastoma multiforme (GBM). This study aimed to assess the potential causal effects of blood pressure (BP) and antihypertensive drugs on GBM. Genome‐wide association study (GWAS) summary statistics for systolic blood pressure (SBP), diastolic blood pressure (DBP), and GBM in Europeans were downloaded. To represent the effects of antihypertensive drugs, we utilized single nucleotide polymorphisms (SNPs) associated with SBP/DBP adjacent to the coding regions of different antihypertensive drugs as instrumental variables to model five antihypertensive drugs, including angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, β‐receptor blockers (BBs), and thiazide diuretics. Positive control studies were performed using GWAS data in chronic heart failure. The primary method for causality estimation was the inverse‐variance‐weighted method. Mendelian randomization analysis showed that BBs with the β1‐adrenergic receptor (ADRB1) as a therapeutic target could significantly reduce the risk of GBM by mediating DBP (OR = 0.431, 95% CI: 0.267–0.697, p < .001) and that they could also significantly reduce the risk of GBM by mediating SBP (OR = 0.595, 95% CI: 0.422–0.837, p = .003). Sensitivity analysis and colocalization analysis reinforced the robustness of these findings. Finally, the low expression of the ADRB1 gene in malignant gliomas was found by GBM data from TCGA and single‐cell RNA sequencing, which most likely contributed to the poor prognosis of GBM patients. In summary, our study provides preliminary evidence of some causal relationship between ADRB1‐targeted BBs and glioblastoma development. However, more studies are needed to validate these findings and further reveal the complex relationship between BP and GBM.

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Do renin–angiotensin system inhibitors influence the recurrence, metastasis, and survival in cancer patients?

Abstract: Supplemental Digital Content is available in the text

Cited by 67 publications

References 85 publications

Cancer stem cells in liver metastasis from colon adenocarcinoma express components of the renin-angiotensin system

Cancer stem cells in liver metastasis from colon adenocarcinoma express components of the renin-angiotensin system

Angiotensin-converting enzyme inhibitors may affect pulmonary function in lymphangioleiomyomatosis

Exploring the causal relationship between antihypertensive drugs and glioblastoma by combining drug target Mendelian randomization study, eQTL colocalization, and single‐cell RNA sequencing

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