{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:14:06Z","timestamp":1760148846765,"version":"build-2065373602"},"reference-count":86,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,11]],"date-time":"2023-06-11T00:00:00Z","timestamp":1686441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundo Europeu de Desenvolvimento Regional","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"Faculty of Medicine, University of Porto (FMUP)","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Tezosentan is a vasodilator drug that was originally developed to treat pulmonary arterial hypertension. It acts by inhibiting endothelin (ET) receptors, which are overexpressed in many types of cancer cells. Endothelin-1 (ET1) is a substance produced by the body that causes blood vessels to narrow. Tezosentan has affinity for both ETA and ETB receptors. By blocking the effects of ET1, tezosentan can help to dilate blood vessels, improve the blood flow, and reduce the workload on the heart. Tezosentan has been found to have anticancer properties due to its ability to target the ET receptors, which are involved in promoting cellular processes such as proliferation, survival, neovascularization, immune cell response, and drug resistance. This review intends to demonstrate the potential of this drug in the field of oncology. Drug repurposing can be an excellent way to improve the known profiles of first-line drugs and to solve several resistance problems of these same antineoplastic drugs.<\/jats:p>","DOI":"10.3390\/cimb45060325","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T03:02:27Z","timestamp":1686538947000},"page":"5118-5131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Repurposing of the Drug Tezosentan for Cancer Therapy"],"prefix":"10.3390","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5370-9586","authenticated-orcid":false,"given":"Eduarda","family":"Ribeiro","sequence":"first","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/ijc.33588","article-title":"Cancer statistics for the year 2020: An overview","volume":"149","author":"Ferlay","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12935-015-0221-1","article-title":"Resistance to cancer chemotherapy: Failure in drug response from ADME to P-gp","volume":"15","author":"Alfarouk","year":"2015","journal-title":"Cancer Cell. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"895","DOI":"10.2174\/1874467215666220214104530","article-title":"Drug Repurposing for Cancer Therapy in the Era of Precision Medicine","volume":"15","author":"To","year":"2022","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3390\/covid2020011","article-title":"A Comprehensive Review of Drug Repurposing Strategies against Known Drug Targets of COVID-19","volume":"2","author":"Khataniar","year":"2022","journal-title":"COVID"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41392-020-00213-8","article-title":"Overcoming cancer therapeutic bottleneck by drug repurposing","volume":"5","author":"Zhang","year":"2020","journal-title":"Signal. Transduct. Target. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40545-020-00282-8","article-title":"Repurposing existing drugs for new uses: A cohort study of the frequency of FDA-granted new indication exclusivities since 1997","volume":"14","author":"Sahragardjoonegani","year":"2021","journal-title":"J. Pharm. Policy Pract."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ribeiro, E., Costa, B., Vasques-N\u00f3voa, F., and Vale, N. (2023). In Vitro Drug Repurposing: Focus on Vasodilators. Cells, 12.","DOI":"10.3390\/cells12040671"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.phrs.2011.01.002","article-title":"Endothelins and their receptors in cancer: Identification of therapeutic targets","volume":"63","author":"Wang","year":"2011","journal-title":"Pharmacol. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1046\/j.1365-2125.2002.01158.x","article-title":"Pharmacokinetics and pharmacodynamics of tezosentan, an intravenous dual endothelin receptor antagonist, following chronic infusion in healthy subjects","volume":"53","author":"Dingemanse","year":"2002","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1097\/01.crd.0000137737.54951.aa","article-title":"Tezosentan in the management of decompensated heart failure","volume":"13","author":"Cheng","year":"2005","journal-title":"Cardiol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1067\/mhj.2001.116760","article-title":"The dual endothelin receptor antagonist tezosentan acutely improves hemodynamic parameters in patients with advanced heart failure","volume":"142","author":"Schalcher","year":"2001","journal-title":"Am. Heart J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/s00228-011-1157-6","article-title":"Hemodynamics and pharmacokinetics of tezosentan, a dual endothelin receptor antagonist, in patients with cirrhosis","volume":"68","author":"Lebrec","year":"2012","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/nrc3546","article-title":"Endothelin 1 in cancer: Biological implications and therapeutic opportunities","volume":"13","author":"Spinella","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/sj.bjc.6700750","article-title":"Endothelin-1: A multifunctional molecule in cancer","volume":"88","author":"Grant","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_15","first-page":"3257","article-title":"Production of endothelin in human cancer cell lines","volume":"50","author":"Kusuhara","year":"1990","journal-title":"Cancer Res."},{"key":"ref_16","first-page":"248","article-title":"High plasma concentrations of endothelin-like immunoreactivities in patients with hepatocellular carcinoma","volume":"88","author":"Nakamuta","year":"1993","journal-title":"Am. J. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/nm0995-944","article-title":"Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate","volume":"1","author":"Nelson","year":"1995","journal-title":"Nat. Med."},{"key":"ref_18","first-page":"56","article-title":"Effects of oncological surgery on endothelin-1 secretion in patients with operable gastric cancer","volume":"15","author":"Franciosi","year":"2000","journal-title":"Int. J. Biol. Mrk."},{"key":"ref_19","first-page":"H686","article-title":"Proliferation and migration of endothelial cells is promoted by endothelins via activation of ETB receptors","volume":"269","author":"Morbidelli","year":"1995","journal-title":"Am. J. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10112","DOI":"10.1016\/S0021-9258(17)36997-1","article-title":"Constitutive endothelin-1 overexpression promotes smooth muscle cell proliferation via an external autocrine loop","volume":"269","author":"Alberts","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1016\/S0002-9440(10)64791-8","article-title":"Role of endothelin-1 in neovascularization of ovarian carcinoma","volume":"157","author":"Salani","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1677\/erc.1.01077","article-title":"Emerging role of the endothelin axis in ovarian tumor progression","volume":"12","author":"Bagnato","year":"2005","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1161\/01.CIR.0000094397.19932.78","article-title":"Endothelin Receptor Blockers in Cardiovascular Disease","volume":"108","author":"Rich","year":"2003","journal-title":"Circulation"},{"key":"ref_24","first-page":"663","article-title":"Endothelin-1 production and decreased endothelin B receptor expression in advanced prostate cancer","volume":"56","author":"Nelson","year":"1996","journal-title":"Cancer Res."},{"key":"ref_25","first-page":"720","article-title":"Expression of endothelin 1 and endothelin A receptor in ovarian carcinoma: Evidence for an autocrine role in tumor growth","volume":"59","author":"Bagnato","year":"1999","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S69","DOI":"10.1097\/00005344-200036051-00023","article-title":"Endothelin receptor expression in colorectal cancer","volume":"36","author":"Ali","year":"2000","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0022-5347(05)66597-4","article-title":"Expression of endothelin receptor a associated with prostate cancer progression","volume":"165","author":"Gohji","year":"2001","journal-title":"J. Urol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1593\/neo.06388","article-title":"Endothelin receptor A blockade enhances taxane effects in prostate cancer","volume":"8","author":"Akhavan","year":"2006","journal-title":"Neoplasia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1054\/bjoc.2001.2193","article-title":"Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET(A) receptor antagonism","volume":"85","author":"Asham","year":"2001","journal-title":"Br. J. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1046\/j.1365-2168.1998.00660.x","article-title":"Raised endothelin 1 levels in patients with colorectal liver metastases","volume":"85","author":"Shankar","year":"1998","journal-title":"Br. J. Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e0089822","DOI":"10.1128\/spectrum.00898-22","article-title":"Epstein-Barr Virus Regulates Endothelin-1 Expression through the ERK\/FOXO1 Pathway in EBV-Associated Gastric Cancer","volume":"11","author":"Liu","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15931","DOI":"10.1038\/s41598-020-72960-1","article-title":"Ambrisentan, an endothelin receptor type A-selective antagonist, inhibits cancer cell migration, invasion, and metastasis","volume":"10","author":"Kappes","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1200\/JCO.2003.04.176","article-title":"Effect of endothelin-A receptor blockade with atrasentan on tumor progression in men with hormone-refractory prostate cancer: A randomized, phase II, placebo-controlled trial","volume":"21","author":"Carducci","year":"2003","journal-title":"J. Clin. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12929-018-0426-4","article-title":"Cancer stem cells as key drivers of tumour progression","volume":"25","author":"Ayob","year":"2018","journal-title":"J. Biomed. Sci."},{"key":"ref_35","first-page":"Xe01","article-title":"Tumour Angiogenesis and Angiogenic Inhibitors: A Review","volume":"9","author":"Yadav","year":"2015","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.leukres.2018.10.005","article-title":"The endothelin receptor type A is a downstream target of Hoxa9 and Meis1 in acute myeloid leukemia","volume":"75","author":"Arabanian","year":"2018","journal-title":"Leuk. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2133\/dmpk.DMPK-11-RV-098","article-title":"Functional significance of genetic polymorphisms in P-glycoprotein (MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2)","volume":"27","author":"Ieiri","year":"2012","journal-title":"Drug. Metab. Pharmacokinet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.bbapap.2009.02.014","article-title":"A synonymous polymorphism in a common MDR1 (ABCB1) haplotype shapes protein function","volume":"1794","author":"Fung","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_39","first-page":"47","article-title":"The effect of ABCB1 polymorphisms on the outcome of breast cancer treatment","volume":"9","author":"Tulsyan","year":"2016","journal-title":"Pharmgenomics Pers. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3892\/ol.2017.6145","article-title":"Prognostic significance of ABCB1 in stage I lung adenocarcinoma","volume":"14","author":"Zou","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1002\/mco2.106","article-title":"Overcoming multidrug resistance by knockout of ABCB1 gene using CRISPR\/Cas9 system in SW620\/Ad300 colorectal cancer cells","volume":"2","author":"Lei","year":"2021","journal-title":"MedComm (2020)"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1136\/ijgc-00009577-200503000-00011","article-title":"Increased cyclooxygenase-2 (COX-2) and P-glycoprotein-170 (MDR1) expression is associated with chemotherapy resistance and poor prognosis. Analysis in ovarian carcinoma patients with low and high survival","volume":"15","author":"Raspollini","year":"2005","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ygyno.2005.08.050","article-title":"Multidrug resistance-related phenotype and apoptosis-related protein expression in ovarian serous carcinomas","volume":"100","author":"Yakirevich","year":"2006","journal-title":"Gynecol. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/sj.bjc.6605185","article-title":"Coexpression of invasive markers (uPA, CD44) and multiple drug-resistance proteins (MDR1, MRP2) is correlated with epithelial ovarian cancer progression","volume":"101","author":"Chen","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1097\/IGC.0000000000000354","article-title":"Clinical significance of the resistance proteins LRP, Pgp, MRP1, MRP3, and MRP5 in epithelial ovarian cancer","volume":"25","author":"Laco","year":"2015","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"50161","DOI":"10.18632\/oncotarget.10324","article-title":"Acquired nintedanib resistance in FGFR1-driven small cell lung cancer: Role of endothelin-A receptor-activated ABCB1 expression","volume":"7","author":"Englinger","year":"2016","journal-title":"Oncotarget"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.eururo.2008.10.003","article-title":"Expression of the endothelin axis in noninvasive and superficially invasive bladder cancer: Relation to clinicopathologic and molecular prognostic parameters","volume":"56","author":"Eltze","year":"2009","journal-title":"Eur. Urol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s004280000362","article-title":"Expression of the endothelin-B receptor in pigment cell lesions of the skin. Evidence for its role as tumor progression marker in malignant melanoma","volume":"438","author":"Demunter","year":"2001","journal-title":"Virchows Arch."},{"key":"ref_49","first-page":"457","article-title":"Expression of endothelin receptor subtypes in bronchial tumors","volume":"23","author":"Regnier","year":"2010","journal-title":"Oncol. Rep."},{"key":"ref_50","first-page":"305","article-title":"Expression and prognostic relevance of endothelin-B receptor in vulvar cancer","volume":"18","author":"Eltze","year":"2007","journal-title":"Oncol. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"E693","DOI":"10.1002\/ijc.27419","article-title":"CD31, EDNRB and TSPAN7 are promising prognostic markers in clear-cell renal cell carcinoma revealed by genome-wide expression analyses of primary tumors and metastases","volume":"131","author":"Wuttig","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/bjc.2013.784","article-title":"Endothelin B receptor expression correlates with tumour angiogenesis and prognosis in oesophageal squamous cell carcinoma","volume":"110","author":"Tanaka","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Vasaikar, S., Tsipras, G., Land\u00e1zuri, N., Costa, H., Wilhelmi, V., Scicluna, P., Cui, H.L., Mohammad, A.A., Davoudi, B., and Shang, M. (2018). Overexpression of endothelin B receptor in glioblastoma: A prognostic marker and therapeutic target?. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4012-7"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1093\/hmg\/10.9.903","article-title":"The endothelin receptor B (EDNRB) promoter displays heterogeneous, site specific methylation patterns in normal and tumor cells","volume":"10","author":"Pao","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.7150\/jca.41004","article-title":"Differences in Endothelin B Receptor Isoforms Expression and Function in Breast Cancer Cells","volume":"11","author":"Halaka","year":"2020","journal-title":"J. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1111\/1759-7714.13474","article-title":"Role of endothelin receptor type B (EDNRB) in lung adenocarcinoma","volume":"11","author":"Wei","year":"2020","journal-title":"Thorac. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Chen, Q.W., Edvinsson, L., and Xu, C.B. (2009). Role of ERK\/MAPK in endothelin receptor signaling in human aortic smooth muscle cells. BMC Cell. Biol., 10.","DOI":"10.1186\/1471-2121-10-52"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.lfs.2012.03.040","article-title":"Permissive role of endothelin receptors in tumor metastasis","volume":"91","author":"Said","year":"2012","journal-title":"Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1634\/stemcells.2005-0414","article-title":"Defining the Conditions for the Generation of Melanocytes from Human Embryonic Stem Cells","volume":"24","author":"Fang","year":"2006","journal-title":"Stem Cells"},{"key":"ref_60","first-page":"1111","article-title":"Targeting the endothelin axis in human melanoma: Combination of endothelin receptor antagonism and alkylating agents","volume":"231","author":"Berger","year":"2006","journal-title":"Exp. Biol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s10637-006-9014-7","article-title":"A Phase II study of bosentan, a dual endothelin receptor antagonist, as monotherapy in patients with stage IV metastatic melanoma","volume":"25","author":"Kefford","year":"2007","journal-title":"Investig. New Drugs"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1158\/0008-5472.CAN-06-2606","article-title":"Endothelin-1 and endothelin-3 promote invasive behavior via hypoxia-inducible factor-1alpha in human melanoma cells","volume":"67","author":"Spinella","year":"2007","journal-title":"Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"11496","DOI":"10.1073\/pnas.96.20.11496","article-title":"An endothelin receptor B antagonist inhibits growth and induces cell death in human melanoma cells in vitro and in vivo","volume":"96","author":"Lahav","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1158\/0008-5472.CAN-03-2344","article-title":"Endothelin B receptor blockade inhibits dynamics of cell interactions and communications in melanoma cell progression","volume":"64","author":"Bagnato","year":"2004","journal-title":"Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"49929","DOI":"10.1074\/jbc.M306930200","article-title":"Endothelin-1 activates endothelial cell nitric-oxide synthase via heterotrimeric G-protein betagamma subunit signaling to protein jinase B\/Akt","volume":"278","author":"Liu","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"Fso44","DOI":"10.4155\/fso.15.44","article-title":"Nitric oxide for cancer therapy","volume":"1","author":"Huerta","year":"2015","journal-title":"Future Sci. OA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/1477-7819-11-118","article-title":"Nitric oxide and cancer: A review","volume":"11","author":"Choudhari","year":"2013","journal-title":"World J. Surg. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/sj.cr.7290133","article-title":"The role of nitric oxide in cancer","volume":"12","author":"Xu","year":"2002","journal-title":"Cell. Res."},{"key":"ref_69","first-page":"1163","article-title":"Nitric oxide inhibits gastric cancer cell growth through the modulation of the Akt pathway","volume":"4","author":"Sang","year":"2011","journal-title":"Mol. Med. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1073\/pnas.041603998","article-title":"Nitric oxide-induced cytostasis and cell cycle arrest of a human breast cancer cell line (MDA-MB-231): Potential role of cyclin D1","volume":"98","author":"Pervin","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1002\/pros.20081","article-title":"Nitrosulindac (NCX 1102): A new nitric oxide-donating non-steroidal anti-inflammatory drug (NO-NSAID), inhibits proliferation and induces apoptosis in human prostatic epithelial cell lines","volume":"61","author":"Huguenin","year":"2004","journal-title":"Prostate"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1158\/1535-7163.291.3.3","article-title":"Antiproliferative effect of nitrosulindac (NCX 1102), a new nitric oxide-donating non-steroidal anti-inflammatory drug, on human bladder carcinoma cell lines","volume":"3","author":"Huguenin","year":"2004","journal-title":"Mol. Cancer Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"440","DOI":"10.2174\/138161210790232211","article-title":"Nitric oxide control of proliferation in nerve cells and in tumor cells of nervous origin","volume":"16","author":"Petazzi","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejphar.2009.04.069","article-title":"The novel NO-donating compound GIT-27NO inhibits in vivo growth of human prostate cancer cells and prevents murine immunoinflammatory hepatitis","volume":"615","author":"Donia","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"492","DOI":"10.4161\/cc.10.3.14727","article-title":"In vitro and in vivo anticancer action of Saquinavir-NO, a novel nitric oxide-derivative of the protease inhibitor saquinavir, on hormone resistant prostate cancer cells","volume":"10","author":"Donia","year":"2011","journal-title":"Cell. Cycle"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.niox.2012.02.003","article-title":"Activation of the BRCA1\/Chk1\/p53\/p21(Cip1\/Waf1) pathway by nitric oxide and cell cycle arrest in human neuroblastoma NB69 cells","volume":"26","author":"Grau","year":"2012","journal-title":"Nitric Oxide"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1016\/j.ejca.2008.12.018","article-title":"Nitric oxide delivery to cancer: Why and how?","volume":"45","author":"Sonveaux","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1158\/0008-5472.CAN-03-1307","article-title":"Adenoviral gene transfer of the human inducible nitric oxide synthase gene enhances the radiation response of human colorectal cancer associated with alterations in tumor vascularity","volume":"64","author":"Wang","year":"2004","journal-title":"Cancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"8015","DOI":"10.1158\/0008-5472.CAN-04-2212","article-title":"Nitric oxide and ionizing radiation synergistically promote apoptosis and growth inhibition of cancer by activating p53","volume":"64","author":"Cook","year":"2004","journal-title":"Cancer Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1016\/j.bmc.2013.02.023","article-title":"Pyridinylpyrimidines selectively inhibit human methionine aminopeptidase-1","volume":"21","author":"Zhang","year":"2013","journal-title":"Bioorg Med. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3772","DOI":"10.1002\/anie.200600757","article-title":"Identification of pyridinylpyrimidines as inhibitors of human methionine aminopeptidases","volume":"45","author":"Hu","year":"2006","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1074\/mcp.RA117.000360","article-title":"Omics Assisted N-terminal Proteoform and Protein Expression Profiling On Methionine Aminopeptidase 1 (MetAP1) Deletion","volume":"17","author":"Jonckheere","year":"2018","journal-title":"Mol. Cell. Proteom."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"63306","DOI":"10.18632\/oncotarget.11216","article-title":"MetAP1 and MetAP2 drive cell selectivity for a potent anti-cancer agent in synergy, by controlling glutathione redox state","volume":"7","author":"Frottin","year":"2016","journal-title":"Oncotarget"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"18148","DOI":"10.1073\/pnas.0608389103","article-title":"Elucidation of the function of type 1 human methionine aminopeptidase during cell cycle progression","volume":"103","author":"Hu","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.2174\/1389450111009011439","article-title":"Methionine aminopeptidases as potential targets for treatment of gastrointestinal cancers and other tumours","volume":"11","author":"Mauriz","year":"2010","journal-title":"Curr. Drug. 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