Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

General Review Article

The Potential Therapeutic Value of Renin-Angiotensin System Inhibitors in the Treatment of Colorectal Cancer

Author(s): Ehsan Tabatabai*, Majid Khazaei, Mohammad R. Parizadeh, Mohammad Nouri, Seyed M. Hassanian, Gordon A Ferns, Mohammad Rahmati and Amir Avan*

Volume 28, Issue 1, 2022

Published on: 11 October, 2021

Page: [71 - 76] Pages: 6

DOI: 10.2174/1381612827666211011113308

Price: $65

Abstract

Colorectal cancer is the third most common cancer globally. Despite extensive preclinical and clinical studies, it is still among the leading causes of cancer-related death, and a need for new therapeutic options is required. The renin-angiotensin system plays an important role in regulating blood pressure and cell growth. In addition to their hemodynamic effects, some of the renin-angiotensin system components, such as angiotensin, are also growth factors that promote cell proliferation and angiogenesis, and its dysregulation is reported to be associated with poor prognosis in colorectal cancer. Here we describe the critical role of the renin-angiotensin system pathway in colorectal cancer as well as the preclinical and clinical investigations renin-angiotensin system inhibitors: angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers as a potential therapeutic target in the treatment of colorectal cancer. Several studies have been shown that the inhibition of these pathways can reduce tumor growth and metastasis; however, some of the data remain inconsistent. There is accumulating evidence of the therapeutic potential of some inhibitors, such as Losartan which are now in clinical phases in the treatment of several malignancies using Nivolumab in combination with FOLFIRINOX in pancreatic cancer. Further investigations are warranted to improve the efficacy and selectivity of current and future anticancer strategies targeting renin-angiotensin systems.

Keywords: Colorectal cancer, renin-angiotensin system, ARBs, ACEIs, prognosis, treatment.

« Previous
[1]
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin 2021; 71(1): 7-33.
[http://dx.doi.org/10.3322/caac.21654] [PMID: 33433946]
[2]
Beitia M, Solano-Iturri JD, Errarte P, et al. Altered expression of renin-angiotensin system receptors throughout colorectal adenoma-adenocarcinoma sequence. Int J Med Sci 2019; 16(6): 813-21.
[http://dx.doi.org/10.7150/ijms.32599] [PMID: 31337954]
[3]
Fyhrquist F, Saijonmaa O. Renin-angiotensin system revisited. J Intern Med 2008; 264(3): 224-36.
[http://dx.doi.org/10.1111/j.1365-2796.2008.01981.x] [PMID: 18793332]
[4]
Perdomo-Pantoja A, Mejía-Pérez SI, Gómez-Flores-Ramos L, et al. Renin angiotensin system and its role in biomarkers and treatment in gliomas. J Neurooncol 2018; 138(1): 1-15.
[http://dx.doi.org/10.1007/s11060-018-2789-5] [PMID: 29450812]
[5]
George AJ, Thomas WG, Hannan RD. The renin-angiotensin system and cancer: old dog, new tricks. Nat Rev Cancer 2010; 10(11): 745-59.
[http://dx.doi.org/10.1038/nrc2945] [PMID: 20966920]
[6]
Ishikane S, Takahashi-Yanaga F. The role of angiotensin II in cancer metastasis: Potential of renin-angiotensin system blockade as a treatment for cancer metastasis. Biochem Pharmacol 2018; 151: 96-103.
[http://dx.doi.org/10.1016/j.bcp.2018.03.008] [PMID: 29534876]
[7]
Tawinwung S, Ninsontia C, Chanvorachote P, Angiotensin II. Angiotensin II increases cancer stem cell-like phenotype in lung cancer cells. Anticancer Res 2015; 35(9): 4789-97.
[PMID: 26254369]
[8]
Nguyen G, Muller DN. The biology of the (pro)renin receptor. J Am Soc Nephrol 2010; 21(1): 18-23.
[http://dx.doi.org/10.1681/ASN.2009030300] [PMID: 19917780]
[9]
Kawai T, Forrester SJ, O'Brien S, Baggett A, Rizzo V, Eguchi S. AT1 receptor signaling pathways in the cardiovascular system. Pharmacol Res 2017; 125(Pt A): 4-13.
[http://dx.doi.org/10.1016/j.phrs.2017.05.008]
[10]
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646-74.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[11]
González-Zuloeta Ladd AM, Arias Vásquez A, Siemes C, et al. Differential roles of Angiotensinogen and Angiotensin Receptor type 1 polymorphisms in breast cancer risk. Breast Cancer Res Treat 2007; 101(3): 299-304.
[http://dx.doi.org/10.1007/s10549-006-9290-0] [PMID: 16823505]
[12]
Romero CA, Orias M, Weir MR. Novel RAAS agonists and antagonists: clinical applications and controversies. Nat Rev Endocrinol 2015; 11(4): 242-52.
[http://dx.doi.org/10.1038/nrendo.2015.6] [PMID: 25666495]
[13]
Perdomo-Pantoja A, Mejía-Pérez SI, Reynoso-Noverón N, et al. Angiotensinogen rs5050 germline genetic variant as potential biomarker of poor prognosis in astrocytoma. PLoS One 2018; 13(11): e0206590.
[http://dx.doi.org/10.1371/journal.pone.0206590] [PMID: 30383794]
[14]
Xu J, Fan J, Wu F, et al. The ACE2/Angiotensin-(1-7)/Mas Receptor Axis: Pleiotropic Roles in Cancer. Front Physiol 2017; 8: 276.
[http://dx.doi.org/10.3389/fphys.2017.00276] [PMID: 28533754]
[15]
Yu C, Tang W, Wang Y, et al. Downregulation of ACE2/Ang-(1-7)/Mas axis promotes breast cancer metastasis by enhancing store-operated calcium entry. Cancer Lett 2016; 376(2): 268-77.
[http://dx.doi.org/10.1016/j.canlet.2016.04.006] [PMID: 27063099]
[16]
Bernardi S, Zennaro C, Palmisano S, et al. Characterization and significance of ACE2 and Mas receptor in human colon adenocarcinoma. J Renin Angiotensin Aldosterone Syst 2012; 13(1): 202-9.
[http://dx.doi.org/10.1177/1470320311426023] [PMID: 22048948]
[17]
Zhou L, Zhang R, Zhang L, Yao W, Li J, Yuan Y. Angiotensin-converting enzyme 2 acts as a potential molecular target for pancreatic cancer therapy. Cancer Lett 2011; 307(1): 18-25.
[http://dx.doi.org/10.1016/j.canlet.2011.03.011] [PMID: 21481527]
[18]
Gallagher PE, Tallant EA. Inhibition of human lung cancer cell growth by angiotensin-(1-7). Carcinogenesis 2004; 25(11): 2045-52.
[http://dx.doi.org/10.1093/carcin/bgh236] [PMID: 15284177]
[19]
Zheng S, Yang Y, Song R, et al. Ang-(1-7) promotes the migration and invasion of human renal cell carcinoma cells via Mas-mediated AKT signaling pathway. Biochem Biophys Res Commun 2015; 460(2): 333-40.
[http://dx.doi.org/10.1016/j.bbrc.2015.03.035] [PMID: 25783053]
[20]
Tanaka N, Miyajima A, Kikuchi E, et al. Prognonstic impact of renin-angiotensin system blockade in localised upper-tract urothelial carcinoma. Br J Cancer 2012; 106(2): 290-6.
[http://dx.doi.org/10.1038/bjc.2011.565] [PMID: 22187036]
[21]
Lever AF, Hole DJ, Gillis CR, et al. Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer? Lancet 1998; 352(9123): 179-84.
[http://dx.doi.org/10.1016/S0140-6736(98)03228-0] [PMID: 9683206]
[22]
Rosenthal T, Gavras I. Angiotensin inhibition and malignancies: a review. J Hum Hypertens 2009; 23(10): 623-35.
[http://dx.doi.org/10.1038/jhh.2009.21] [PMID: 19339998]
[23]
Meier CR, Derby LE, Jick SS, Jick H. Angiotensin-converting enzyme inhibitors, calcium channel blockers, and breast cancer. Arch Intern Med 2000; 160(3): 349-53.
[http://dx.doi.org/10.1001/archinte.160.3.349] [PMID: 10668837]
[24]
Pfeffer MA, Swedberg K, Granger CB, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003; 362(9386): 759-66.
[http://dx.doi.org/10.1016/S0140-6736(03)14282-1] [PMID: 13678868]
[25]
Yoon C, Yang HS, Jeon I, Chang Y, Park SM. Use of angiotensin- converting-enzyme inhibitors or angiotensin-receptor blockers and cancer risk: a meta-analysis of observational studies. CMAJ 2011; 183(14): E1073-84.
[http://dx.doi.org/10.1503/cmaj.101497] [PMID: 21876027]
[26]
Robles NR, Cerezo I, Hernandez-Gallego R. Renin-angiotensin system blocking drugs. J Cardiovasc Pharmacol Ther 2014; 19(1): 14-33.
[http://dx.doi.org/10.1177/1074248413501018] [PMID: 24038019]
[27]
Ranjbar R, Shafiee M, Hesari A, Ferns GA, Ghasemi F, Avan A. The potential therapeutic use of renin-angiotensin system inhibitors in the treatment of inflammatory diseases. J Cell Physiol 2019; 234(3): 2277-95.
[http://dx.doi.org/10.1002/jcp.27205] [PMID: 30191985]
[28]
Maibaum J, Stutz S, Göschke R, et al. Structural modification of the P2′ position of 2,7-dialkyl-substituted 5(S)-amino-4(S)-hydroxy-8-phenyl-octanecarboxamides: the discovery of aliskiren, a potent nonpeptide human renin inhibitor active after once daily dosing in marmosets. J Med Chem 2007; 50(20): 4832-44.
[http://dx.doi.org/10.1021/jm070316i] [PMID: 17824680]
[29]
Matthew J. Munro, Agadha C Wickremesekera, Paul F Davis, Reginald Marsh, Itinteang STTaT. Renin-angiotensin system and cancer: A review. Integr Cancer Sci Ther 2017.
[30]
Riordan JF. Angiotensin-I-converting enzyme and its relatives. Genome Biol 2003; 4(8): 225.
[http://dx.doi.org/10.1186/gb-2003-4-8-225] [PMID: 12914653]
[31]
Herman LL, Padala SA, Annamaraju P, Bashir K. Angiotensin Converting Enzyme Inhibitors (ACEI). Treasure Island, FL: StatPearls 2020.
[32]
Aalbers J. Angiotensin receptor blockers (ARBs) in hypertension patients: earlier use of these better-tolerated medications is warranted. Cardiovasc J Afr 2010; 21(2): 124.
[PMID: 20532444]
[33]
Barreras A, Gurk-Turner C. Angiotensin II receptor blockers. Proc Bayl Univ Med Cent 2003; 16(1): 123-6.
[http://dx.doi.org/10.1080/08998280.2003.11927893] [PMID: 16278727]
[34]
Burnier M, Brunner HR. Angiotensin II receptor antagonists. Lancet 2000; 355(9204): 637-45.
[http://dx.doi.org/10.1016/S0140-6736(99)10365-9] [PMID: 10696996]
[35]
Burnier M. Angiotensin II type 1 receptor blockers. Circulation 2001; 103(6): 904-12.
[http://dx.doi.org/10.1161/01.CIR.103.6.904] [PMID: 11171802]
[36]
Bradshaw A, Wickremesekera A, Brasch HD, et al. Cancer Stem Cells in Glioblastoma Multiforme. Front Surg 2016; 3: 48.
[PMID: 27617262]
[37]
Ager EI, Neo J, Christophi C. The renin-angiotensin system and malignancy. Carcinogenesis 2008; 29(9): 1675-84.
[http://dx.doi.org/10.1093/carcin/bgn171] [PMID: 18632755]
[38]
Childers WK. Interactions of the renin-angiotensin system in colorectal cancer and metastasis. Int J Colorectal Dis 2015; 30(6): 749-52.
[http://dx.doi.org/10.1007/s00384-014-2118-1] [PMID: 25592047]
[39]
Holmes S, Griffith EJ, Musto G, Minuk GY. Antihypertensive medications and survival in patients with cancer: a population-based retrospective cohort study. Cancer Epidemiol 2013; 37(6): 881-5.
[http://dx.doi.org/10.1016/j.canep.2013.09.001] [PMID: 24075077]
[40]
Dolley-Hitze T, Jouan F, Martin B, et al. Angiotensin-2 receptors (AT1-R and AT2-R), new prognostic factors for renal clear-cell carcinoma? Br J Cancer 2010; 103(11): 1698-705.
[http://dx.doi.org/10.1038/sj.bjc.6605866] [PMID: 21102591]
[41]
Neo JH, Malcontenti-Wilson C, Muralidharan V, Christophi C. Effect of ACE inhibitors and angiotensin II receptor antagonists in a mouse model of colorectal cancer liver metastases. J Gastroenterol Hepatol 2007; 22(4): 577-84.
[http://dx.doi.org/10.1111/j.1440-1746.2006.04797.x] [PMID: 17376054]
[42]
Shimizu Y, Amano H, Ito Y, et al. Angiotensin II subtype 1a receptor signaling in resident hepatic macrophages induces liver metastasis formation. Cancer Sci 2017; 108(9): 1757-68.
[http://dx.doi.org/10.1111/cas.13306] [PMID: 28660748]
[43]
Ozawa T, Hashiguchi Y, Yagi T, et al. Angiotensin I-converting enzyme inhibitors/angiotensin II receptor blockers may reduce tumor recurrence in left-sided and early colorectal cancers. Int J Colorectal Dis 2019; 34(10): 1731-9.
[http://dx.doi.org/10.1007/s00384-019-03379-y] [PMID: 31478086]
[44]
Pinter M, Jain RK. Targeting the renin-angiotensin system to improve cancer treatment: Implications for immunotherapy. Sci Transl Med 2017; 9(410): eaan5616.
[http://dx.doi.org/10.1126/scitranslmed.aan5616] [PMID: 28978752]
[45]
Collaboration ARBT. Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138,769 individuals. J Hypertens 2011; 29(4): 623-35.
[http://dx.doi.org/10.1097/HJH.0b013e328344a7de] [PMID: 21358417]
[46]
Moreno-Muñoz D, de la Haba-Rodríguez JR, Conde F, et al. Genetic variants in the renin-angiotensin system predict response to bevacizumab in cancer patients. Eur J Clin Invest 2015; 45(12): 1325-32.
[http://dx.doi.org/10.1111/eci.12557] [PMID: 26509357]
[47]
Sun H, Li T, Zhuang R, Cai W, Zheng Y. Do renin-angiotensin system inhibitors influence the recurrence, metastasis, and survival in cancer patients?: Evidence from a meta-analysis including 55 studies. Medicine (Baltimore) 2017; 96(13): e6394.
[http://dx.doi.org/10.1097/MD.0000000000006394] [PMID: 28353566]
[48]
Narayanan Anantha. Cancer stem cells in liver metastasis from colon adenocarcinoma express components of the renin-angiotensin system. J Cancer Metastasis Treat 2019; 5: 36.
[49]
Chauhan VP, Martin JD, Liu H, et al. Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels. Nat Commun 2013; 4: 2516.
[http://dx.doi.org/10.1038/ncomms3516] [PMID: 24084631]
[50]
Beitia M, Solano-Iturri JD, Errarte P, et al. (Pro)renin receptor expression increases throughout the colorectal adenoma-adenocarcinoma sequence and it is associated with worse colorectal cancer prognosis. Cancers (Basel) 2019; 11(6): E881.
[http://dx.doi.org/10.3390/cancers11060881] [PMID: 31238566]
[51]
Kuniyasu H. Multiple roles of angiotensin in colorectal cancer. World J Clin Oncol 2012; 3(12): 150-4.
[http://dx.doi.org/10.5306/wjco.v3.i12.150] [PMID: 23293754]
[52]
Dai YN, Wang JH, Zhu JZ, Lin JQ, Yu CH, Li YM. Angiotensin- converting enzyme inhibitors/angiotensin receptor blockers therapy and colorectal cancer: a systematic review and meta-analysis. Cancer Causes Control 2015; 26(9): 1245-55.
[http://dx.doi.org/10.1007/s10552-015-0617-1] [PMID: 26081426]
[53]
Wen SW, Ager EI, Neo J, Christophi C. The renin angiotensin system regulates Kupffer cells in colorectal liver metastases. Cancer Biol Ther 2013; 14(8): 720-7.
[http://dx.doi.org/10.4161/cbt.25092] [PMID: 23792575]
[54]
Zhang K, Mao T, He Z, et al. Angiotensin I-converting enzyme gene plays a crucial role in the pathology of carcinomas in colorectal cancer. Artif Cells Nanomed Biotechnol 2019; 47(1): 2500-6.
[http://dx.doi.org/10.1080/21691401.2019.1626402] [PMID: 31203648]
[55]
Shimizu Y, Amano H, Ito Y, et al. The role of angiotensin II in liver metastasis formation from colorectal cancer. Kitasato Med J 2017; 2017(47): 43-51.
[56]
Koh SL, Ager EI, Costa PL, Malcontenti-Wilson C, Muralidharan V, Christophi C. Blockade of the renin-angiotensin system inhibits growth of colorectal cancer liver metastases in the regenerating liver. Clin Exp Metastasis 2014; 31(4): 395-405.
[http://dx.doi.org/10.1007/s10585-014-9635-8] [PMID: 24442969]
[57]
Valuckaite V, Ruderman S, Almoghrabi A, et al. A novel use of angiotensin II receptor blocker (ARB) losartan to inhibit AOM induced tumorigenesis and neoangiogenesis in experimental colon cancer. Gastroenterology 2015; 148(4)(Suppl. 1): S-172.
[http://dx.doi.org/10.1016/S0016-5085(15)30574-6]
[58]
Tascilar K, Azoulay L, Dell’Aniello S, Bartels DB, Suissa S. The use of telmisartan and the incidence of cancer. Am J Hypertens 2016; 29(12): 1358-65.
[http://dx.doi.org/10.1093/ajh/hpw095] [PMID: 27557862]
[59]
Yue Z, Yun-Shan Z, Feng-Xia X. miR-205 mediates the inhibition of cervical cancer cell proliferation using olmesartan. J Renin Angiotensin Aldosterone Syst 2016; 17(3): 1470320316663327.
[http://dx.doi.org/10.1177/1470320316663327] [PMID: 28304186]
[60]
Bakhtiari E, Hosseini A, Boroushaki MT, Mousavi SH. Angiotensin II receptor antagonist olmesartan and NF-kappaB inhibitor as cytotoxic and apoptotic agents in MCF-7 human cell line. J Chemother 2016; 28(4): 314-20.
[http://dx.doi.org/10.1179/1973947815Y.0000000055] [PMID: 26138656]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy