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

George, Amee J.; Thomas, Walter G.; Hannan, Ross D.

doi:10.1038/nrc2945

Cited by 455 publications

(540 citation statements)

References 185 publications

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“…5 It is likely that dysregulation of the normal physiological actions of the RAS in inflammation and angiogenesis might function to synergistically promote growth during malignancy. 8 Some reports using an AT1R antagonist and AT1R genedeficient (AT1a-/-) mice have shown that blocking AT1R signalling inhibited the growth of the following cells type: vascular endothelial, 19 prostate, 20 renal cell carcinoma 21 and pancreas. 22 In 2007, Imai and colleagues determined that AT1R-induced vascular endothelial growth factor a (VEGFa) signalling, in both host and tumour tissues, is one of the key regulators of tumour growth and tumour-associated angiogenesis.…”

Section: Inducing Angiogenesismentioning

confidence: 99%

“…8 A hypoxic tumour environment, coupled with excessive accumulation of ROS, leads to oxidative stress, followed by increased protein modifications, cellular damage and death or increased growth factor signalling. 28 AngII induces the expression of p47phox and the production of the O2-radical through the activation of the AT1R in prostate cancer cells.…”

Section: Reprogramming Of Energy Metabolismmentioning

confidence: 99%

“…8 Signaling through the AT2R is linked to the promotion of apoptosis. In prostate cancer cells, AT2R overexpression induced apoptosis independently of AngII but was dependent on p38 mitogen-activated protein kinase (MAPK), caspase 8 and caspase 3 and was mediated through an extrinsic cell death-signalling pathway that was partially dependent on TP53, but not P21, activation.…”

Section: Resisting Cell Deathmentioning

confidence: 99%

“…8 The most studied components of the RAS, in the process of cell proliferation, are AngII and its receptors, which induce hyperplasia or hypertrophy in cultured vascular smooth muscle cells derived from the aorta. Interestingly, AngII has antagonist functions.…”

Section: Proliferative Signallingmentioning

confidence: 99%

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The renin-angiotensin system meets the hallmarks of cancer

Wegman-Ostrosky

Soto-Reyes

Vidal-Millán

et al. 2013

J Renin Angiotensin Aldosterone Syst

134

156

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The classical view of the RAS is presented as a hormonal circulating system that is centred on the active peptide Angiotensin II (AngII). Angiotensinogen (AGT) is synthesised and released by the liver into the blood flow in response to decreased blood pressure or plasma sodium. The juxtaglo merular cells of the kidneys release aspartyl protease renin, which cleaves AGT at its N-terminus, AbstractThe hallmarks of cancer are described as the distinctive and complementary capacities that cells must acquire during the multistep development of becoming a cancer cell that allow them to survive, proliferate and disseminate. The reninangiotensin system (RAS) was first discovered and extensively studied in the physiological regulation of systemic arterial pressure. RAS signalling increases cell proliferation in malignancy by directly affecting tumour and stromal cells and by indirectly modulating the growth of vascular cells during angiogenesis. We aim to describe and give a general view of how the RAS is involved in several hallmarks of cancer and how this could open a window to several interesting treatments.

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Section: Inducing Angiogenesismentioning

confidence: 99%

Section: Reprogramming Of Energy Metabolismmentioning

confidence: 99%

Section: Resisting Cell Deathmentioning

confidence: 99%

Section: Proliferative Signallingmentioning

confidence: 99%

See 2 more Smart Citations

The renin-angiotensin system meets the hallmarks of cancer

Wegman-Ostrosky

Soto-Reyes

Vidal-Millán

et al. 2013

J Renin Angiotensin Aldosterone Syst

134

156

View full text Add to dashboard Cite

show abstract

“…Taking p53 gene for example, the computed gene weights suggest that it acts as a core gene in pathways such as the p53 hypoxia signaling pathway ( Figure 1B) and p53 signaling pathway (with a high weight ranking top 1), and it participates but not dominates in pathways such as Huntington's disease pathway and cell cycle checkpoint pathway (ranking 72 and 102, respectively; Supplementary information, Table S1). Another example is the EGFR gene, which is suggested to be a more central gene in some pathways (such as AT1R pathway [27] and EGF pathway [28]) than others (such as calcium signaling pathway [29] and cytokine-cytokine receptor interaction [30]) (Supplementary information, Table S2). We have tested another functional association network named FunCoup [31], which produced similar gene weights in the pathways, with p53 hypoxia signaling pathway again taken as an example ( Figure 1C).…”

Section: Strategy Of Network-based Gene Weighting Within Pathwaysmentioning

confidence: 99%

A network-based gene-weighting approach for pathway analysis

Fang

Tian

2011

Cell Res

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Classical algorithms aiming at identifying biological pathways significantly related to studying conditions frequently reduced pathways to gene sets, with an obvious ignorance of the constitutive non-equivalence of various genes within a defined pathway. We here designed a network-based method to determine such non-equivalence in terms of gene weights. The gene weights determined are biologically consistent and robust to network perturbations. By integrating the gene weights into the classical gene set analysis, with a subsequent correction for the "over-counting" bias associated with multi-subunit proteins, we have developed a novel gene-weighed pathway analysis approach, as implemented in an R package called "Gene Associaqtion Network-based Pathway Analysis" (GANPA). Through analysis of several microarray datasets, including the p53 dataset, asthma dataset and three breast cancer datasets, we demonstrated that our approach is biologically reliable and reproducible, and therefore helpful for microarray data interpretation and hypothesis generation.

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Total Neoadjuvant Therapy With FOLFIRINOX in Combination With Losartan Followed by Chemoradiotherapy for Locally Advanced Pancreatic Cancer

et al. 2019

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IMPORTANCEPatients with locally advanced pancreatic cancer have historically poor outcomes. Evaluation of a total neoadjuvant approach is warranted. OBJECTIVE To evaluate the margin-negative (R0) resection rate of neoadjuvant FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) and losartan followed by chemoradiotherapy for locally advanced pancreatic cancer. DESIGN, SETTING, AND PARTICIPANTSA single-arm phase 2 clinical trial was conducted at a large academic hospital from August 22, 2013, to May 22, 2018, among 49 patients with previously untreated locally advanced unresectable pancreatic cancer as determined by multidisciplinary review. Patients had Eastern Cooperative Oncology Group performance status 0 or 1 and adequate hematologic, renal, and hepatic function. Median follow-up for the analysis was 17.1 months (range, 5.0-53.7) among 27 patients still alive at study completion. INTERVENTIONS Patients received FOLFIRINOX and losartan for 8 cycles. Patients with radiographically resectable tumor after chemotherapy received short-course chemoradiotherapy (5 GyE × 5 with protons) with capecitabine. Patients with persistent vascular involvement received long-course chemoradiotherapy (50.4 Gy with a vascular boost to 58.8 Gy) with fluorouracil or capecitabine. MAIN OUTCOMES AND MEASURES R0 resection rate. RESULTSOf the 49 patients (26 women and 23 men; median age 63 years [range, 42-78 years]), 39 completed 8 cycles of FOLFIRINOX and losartan; 10 patients had fewer than 8 cycles due to progression (5 patients), losartan intolerance (3 patients), and toxicity (2 patients). Seven patients (16%) had short-course chemoradiotherapy while 38 (84%) had long-course chemoradiotherapy. Forty-two (86%) patients underwent attempted surgery, with R0 resection achieved in 34 of 49 patients (69%; 95% CI, 55%-82%). Overall median progression-free survival was 17.5 months (95% CI: 13.9-22.7) and median overall survival was 31.4 months (95% CI, 18.1-38.5). Among patients who underwent resection, median progression-free survival was 21.3 months (95% CI, 16.6-28.2), and median overall survival was 33.0 months (95% CI, 31.4 to not reached).CONCLUSIONS AND RELEVANCE Total neoadjuvant therapy with FOLFIRINOX, losartan, and chemoradiotherapy provides downstaging of locally advanced pancreatic ductal adenocarcinoma and is associated with an R0 resection rate of 61%.

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

Cited by 455 publications

References 185 publications

The renin-angiotensin system meets the hallmarks of cancer

The renin-angiotensin system meets the hallmarks of cancer

A network-based gene-weighting approach for pathway analysis

Total Neoadjuvant Therapy With FOLFIRINOX in Combination With Losartan Followed by Chemoradiotherapy for Locally Advanced Pancreatic Cancer

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