{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:27:32Z","timestamp":1790519252290,"version":"4.1.0"},"reference-count":75,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T00:00:00Z","timestamp":1602547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002081","name":"Irish Research Council","doi-asserted-by":"publisher","award":["EBP\/2017\/473"],"award-info":[{"award-number":["EBP\/2017\/473"]}],"id":[{"id":"10.13039\/501100002081","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020","doi-asserted-by":"publisher","award":["734907 (RISE\/3D-NEONET project)"],"award-info":[{"award-number":["734907 (RISE\/3D-NEONET project)"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Breakthrough Cancer Research","award":["BCR-2019-01-UCD"],"award-info":[{"award-number":["BCR-2019-01-UCD"]}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["15\/IA\/3104"],"award-info":[{"award-number":["15\/IA\/3104"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["18\/SPP\/3522"],"award-info":[{"award-number":["18\/SPP\/3522"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Metastatic uveal melanoma (UM) is a rare, but often lethal, form of ocular cancer arising from melanocytes within the uveal tract. UM has a high propensity to spread hematogenously to the liver, with up to 50% of patients developing liver metastases. Unfortunately, once liver metastasis occurs, patient prognosis is extremely poor with as few as 8% of patients surviving beyond two years. There are no standard-of-care therapies available for the treatment of metastatic UM, hence it is a clinical area of urgent unmet need. Here, the clinical relevance and therapeutic potential of cysteinyl leukotriene receptors (CysLT1 and CysLT2) in UM was evaluated. High expression of CYSLTR1 or CYSLTR2 transcripts is significantly associated with poor disease-free survival and poor overall survival in UM patients. Digital pathology analysis identified that high expression of CysLT1 in primary UM is associated with reduced disease-specific survival (p = 0.012; HR 2.76; 95% CI 1.21\u20136.3) and overall survival (p = 0.011; HR 1.46; 95% CI 0.67\u20133.17). High CysLT1 expression shows a statistically significant (p = 0.041) correlation with ciliary body involvement, a poor prognostic indicator in UM. Small molecule drugs targeting CysLT1 were vastly superior at exerting anti-cancer phenotypes in UM cell lines and zebrafish xenografts than drugs targeting CysLT2. Quininib, a selective CysLT1 antagonist, significantly inhibits survival (p &lt; 0.0001), long-term proliferation (p &lt; 0.0001), and oxidative phosphorylation (p &lt; 0.001), but not glycolysis, in primary and metastatic UM cell lines. Quininib exerts opposing effects on the secretion of inflammatory markers in primary versus metastatic UM cell lines. Quininib significantly downregulated IL-2 and IL-6 in Mel285 cells (p &lt; 0.05) but significantly upregulated IL-10, IL-1\u03b2, IL-2 (p &lt; 0.0001), IL-13, IL-8 (p &lt; 0.001), IL-12p70 and IL-6 (p &lt; 0.05) in OMM2.5 cells. Finally, quininib significantly inhibits tumour growth in orthotopic zebrafish xenograft models of UM. These preclinical data suggest that antagonism of CysLT1, but not CysLT2, may be of therapeutic interest in the treatment of UM.<\/jats:p>","DOI":"10.3390\/cancers12102950","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T21:42:21Z","timestamp":1602798141000},"page":"2950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["High Cysteinyl Leukotriene Receptor 1 Expression Correlates with Poor Survival of Uveal Melanoma Patients and Cognate Antagonist Drugs Modulate the Growth, Cancer Secretome, and Metabolism of Uveal Melanoma Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5566-8399","authenticated-orcid":false,"given":"Kayleigh","family":"Slater","sequence":"first","affiliation":[{"name":"UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland"},{"name":"Genomics Medicine Ireland Limited, Cherrywood Business Park Building 4, D18 K7W4 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisling B.","family":"Heeran","sequence":"additional","affiliation":[{"name":"Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, St. James\u2019s Hospital, D08 W9RT Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4931-1267","authenticated-orcid":false,"given":"Sandra","family":"Garcia-Mulero","sequence":"additional","affiliation":[{"name":"Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L\u2019Hospitalet de Llobregat, 08908 Barcelona, Spain"},{"name":"Department of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Kalirai","sequence":"additional","affiliation":[{"name":"Liverpool Ocular Oncology Research Group, Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L7 8TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2187-3527","authenticated-orcid":false,"given":"Rebeca","family":"Sanz-Pamplona","sequence":"additional","affiliation":[{"name":"Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L\u2019Hospitalet de Llobregat, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arman","family":"Rahman","sequence":"additional","affiliation":[{"name":"UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4669-4648","authenticated-orcid":false,"given":"Nebras","family":"Al-Attar","sequence":"additional","affiliation":[{"name":"UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mays","family":"Helmi","sequence":"additional","affiliation":[{"name":"Unit of Cardiovascular Medicine, Division of Diagnostics and Specialist Medicine, Department of Health, Medical and Caring Sciences, Link\u00f6ping University, SE-581 83 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3641-4374","authenticated-orcid":false,"given":"Fiona","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, St. James\u2019s Hospital, D08 W9RT Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Bosch","sequence":"additional","affiliation":[{"name":"Xenopat S.L., Parc Cient\u00edfic de Barcelona, Baldiri Reixac, 15-21 Edifici H\u00e8lix, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Portela","sequence":"additional","affiliation":[{"name":"Xenopat S.L., Parc Cient\u00edfic de Barcelona, Baldiri Reixac, 15-21 Edifici H\u00e8lix, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Villanueva","sequence":"additional","affiliation":[{"name":"Xenopat S.L., Parc Cient\u00edfic de Barcelona, Baldiri Reixac, 15-21 Edifici H\u00e8lix, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4307-5999","authenticated-orcid":false,"given":"William M.","family":"Gallagher","sequence":"additional","affiliation":[{"name":"UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2338-357X","authenticated-orcid":false,"given":"Lasse D.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Unit of Cardiovascular Medicine, Division of Diagnostics and Specialist Medicine, Department of Health, Medical and Caring Sciences, Link\u00f6ping University, SE-581 83 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep M.","family":"Piulats","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Catalan Institute of Cancer (ICO), IDIBELL-OncoBell, Hospitalet de Llobregat, 08908 Barcelona, Spain"},{"name":"Clinical Research in Solid Tumors Group (CREST), Bellvitge Biomedical Research Institute IDIBELL-OncoBell, CIBERONC, Hospitalet de Llobregat, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1464-2069","authenticated-orcid":false,"given":"Sarah E.","family":"Coupland","sequence":"additional","affiliation":[{"name":"Liverpool Ocular Oncology Research Group, Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L7 8TX, UK"},{"name":"Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Foundation Trust, Liverpool L69 3GA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacintha","family":"O\u2019Sullivan","sequence":"additional","affiliation":[{"name":"Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, St. James\u2019s Hospital, D08 W9RT Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7991-4689","authenticated-orcid":false,"given":"Breand\u00e1n N.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.5114\/jcb.2017.70986","article-title":"Patterns of care and survival outcomes after treatment for uveal melanoma in the post-coms era (2004-2013): A surveillance, epidemiology, and end results analysis","volume":"5","author":"Rao","year":"2017","journal-title":"J. Contemp. Brachytherapy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/eye.2012.242","article-title":"Personalized treatment of uveal melanoma","volume":"27","author":"Damato","year":"2012","journal-title":"Eye"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1001\/archopht.123.12.1639","article-title":"Development of Metastatic Disease After Enrollment in the COMS Trials for Treatment of Choroidal Melanoma","volume":"123","author":"Reynolds","year":"2005","journal-title":"Arch. Ophthalmol."},{"key":"ref_4","first-page":"848","article-title":"Prognosis of Mucosal, Uveal, Acral, Nonacral Cutaneous, and Unknown Primary Melanoma from the Time of First Metastasis","volume":"21","author":"Kuk","year":"2016","journal-title":"Oncology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1159\/000495113","article-title":"Uveal Melanoma Metastatic to the Liver: Treatment Trends and Outcomes","volume":"5","author":"Xu","year":"2019","journal-title":"Ocul. Oncol. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1097\/CMR.0b013e3283457726","article-title":"Metastatic uveal melanoma","volume":"21","author":"Pons","year":"2011","journal-title":"Melanoma Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2147\/TACG.S69210","article-title":"The genetics of uveal melanoma: Current insights","volume":"9","author":"Hoiom","year":"2016","journal-title":"Appl. Clin. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ccell.2017.07.003","article-title":"Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma","volume":"32","author":"Robertson","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s10555-018-9751-z","article-title":"Evaluation of oncogenic cysteinyl leukotriene receptor 2 as a therapeutic target for uveal melanoma","volume":"37","author":"Slater","year":"2018","journal-title":"Cancer Metastasis Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1056\/NEJMoa1000584","article-title":"Mutations inGNA11in Uveal Melanoma","volume":"363","author":"Griewank","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41572-020-0158-0","article-title":"Uveal melanoma","volume":"6","author":"Jager","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/ng.3549","article-title":"Recurrent activating mutations of G-protein-coupled receptor CYSLTR2 in uveal melanoma","volume":"48","author":"Moore","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nrclinonc.2017.43","article-title":"Targeted agents and immunotherapies: Optimizing outcomes in melanoma","volume":"14","author":"Luke","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Croce, M., Ferrini, S., Pfeffer, U., and Gangemi, R. (2019). Targeted Therapy of Uveal Melanoma: Recent Failures and New Perspectives. Cancers, 11.","DOI":"10.3390\/cancers11060846"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1200\/JCO.2017.74.1090","article-title":"Selumetinib in Combination with Dacarbazine in Patients With Metastatic Uveal Melanoma: A Phase III, Multicenter, Randomized Trial (SUMIT)","volume":"36","author":"Carvajal","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1159\/000312669","article-title":"Cysteinyl Leukotrienes and Their Receptors: Molecular and Functional Characteristics","volume":"85","author":"Singh","year":"2010","journal-title":"Pharmacology"},{"key":"ref_17","first-page":"789","article-title":"Characterization of the human cysteinyl leukotriene CysLT1 receptor","volume":"399","author":"Lynch","year":"1999","journal-title":"Nat. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"30531","DOI":"10.1074\/jbc.M003490200","article-title":"Characterization of the Human Cysteinyl Leukotriene 2 Receptor","volume":"275","author":"Heise","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1182\/blood-2007-07-100453","article-title":"CysLT2 receptors interact with CysLT1 receptors and down-modulate cysteinyl leukotriene\u2013dependent mitogenic responses of mast cells","volume":"110","author":"Jiang","year":"2007","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-13348-2","article-title":"Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors","volume":"10","author":"Gusach","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3389\/fcell.2016.00103","article-title":"Evaluation of Cysteinyl Leukotriene Signaling as a Therapeutic Target for Colorectal Cancer","volume":"4","author":"Burke","year":"2016","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1073\/pnas.1817325115","article-title":"Cysteinyl leukotriene 2 receptor promotes endothelial permeability, tumor angiogenesis, and metastasis","volume":"116","author":"Duah","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"23979","DOI":"10.1038\/srep23979","article-title":"Cysteinyl Leukotriene Receptor Antagonists Decrease Cancer Risk in Asthma Patients","volume":"6","author":"Tsai","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_24","first-page":"185","article-title":"The cysteinylLT1 receptor in human renal cell carcinoma","volume":"1","author":"Kawahito","year":"2011","journal-title":"Mol. Med. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/j.urology.2008.11.005","article-title":"Relationship Between Cysteinyl-Leukotriene-1 Receptor and Human Transitional Cell Carcinoma in Bladder","volume":"73","author":"Matsuyama","year":"2009","journal-title":"Urology"},{"key":"ref_26","first-page":"163","article-title":"Expression of cysteinylLT1 receptor in human testicular cancer and growth reduction by its antagonist through apoptosis","volume":"2","author":"Matsuyama","year":"2009","journal-title":"Mol. Med. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/978-1-4419-9194-2_43","article-title":"The Leukotriene Receptor CYSLT1 and 5- Lipoxygenase Are Upregulated In Colon Cancer","volume":"525","author":"Nielsen","year":"2003","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.ejca.2009.12.022","article-title":"Low expression of CysLT1R and high expression of CysLT2R mediate good prognosis in colorectal cancer","volume":"46","author":"Magnusson","year":"2010","journal-title":"Eur. J. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/ijc.25648","article-title":"Cysteinyl leukotriene receptor expression pattern affects migration of breast cancer cells and survival of breast cancer patients","volume":"129","author":"Magnusson","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_30","first-page":"350","article-title":"Activating cysteinyl leukotriene receptor 2 (CYSLTR2) mutations in blue nevi","volume":"30","author":"Murali","year":"2016","journal-title":"Mod. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1016\/j.jid.2017.04.022","article-title":"Activating CYSLTR2 and PLCB4 Mutations in Primary Leptomeningeal Melanocytic Tumors","volume":"137","author":"Koelsche","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7242","DOI":"10.1074\/jbc.M115.710665","article-title":"Phenotype-based Discovery of 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol as a Novel Regulator of Ocular Angiogenesis","volume":"291","author":"Reynolds","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1074\/jbc.M116.747766","article-title":"A Quininib Analogue and Cysteinyl Leukotriene Receptor Antagonist Inhibits Vascular Endothelial Growth Factor (VEGF)-independent Angiogenesis and Exerts an Additive Antiangiogenic Response with Bevacizumab","volume":"292","author":"Butler","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"srep34523","DOI":"10.1038\/srep34523","article-title":"Preclinical validation of the small molecule drug quininib as a novel therapeutic for colorectal cancer","volume":"6","author":"Murphy","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3725","DOI":"10.18632\/oncotarget.26966","article-title":"1,4-dihydroxy quininib attenuates growth of colorectal cancer cells and xenografts and regulates the TIE-2 signaling pathway in patient tumours","volume":"10","author":"Butler","year":"2019","journal-title":"Oncotarget"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Castet, F., Garcia-Mulero, S., Sanz-Pamplona, R., Cuellar, A., Casanovas, O., Caminal, J.M., and Piulats, J.M. (2019). Uveal Melanoma, Angiogenesis and Immunotherapy, Is There Any Hope?. Cancers, 11.","DOI":"10.3390\/cancers11060834"},{"key":"ref_37","first-page":"2900","article-title":"Microvessel count predicts survival in uveal melanoma","volume":"56","author":"Foss","year":"1996","journal-title":"Cancer Res."},{"key":"ref_38","first-page":"2471","article-title":"Microvascular density in predicting survival of patients with choroidal and ciliary body melanoma","volume":"40","author":"Summanen","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1001\/jamaophthalmol.2014.5395","article-title":"International Validation of the American Joint Committee on Cancer\u2019s 7th Edition Classification of Uveal Melanoma","volume":"133","author":"Simpson","year":"2015","journal-title":"JAMA Ophthalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.preteyeres.2011.05.003","article-title":"Estimating prognosis for survival after treatment of choroidal melanoma","volume":"30","author":"Damato","year":"2011","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_41","first-page":"T5","article-title":"Uveal Melanoma Cell Lines: Where do they come from? (An American Ophthalmological Society Thesis)","volume":"114","author":"Jager","year":"2016","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.1038\/srep03274","article-title":"Cysteinyl leukotrienes regulate endothelial cell inflammatory and proliferative signals through CysLT2 and CysLT1 receptors","volume":"3","author":"Duah","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S214","DOI":"10.1164\/ajrccm.157.6.mar-2","article-title":"Pharmacology of Leukotriene Receptor Antagonists","volume":"157","author":"Aharony","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/j.1476-5381.2010.00730.x","article-title":"Pharmacological characterization of the first potent and selective antagonist at the cysteinyl leukotriene 2 (CysLT2) receptor","volume":"160","author":"Wunder","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1758834018757175","DOI":"10.1177\/1758834018757175","article-title":"Treatment of uveal melanoma: Where are we now?","volume":"10","author":"Yang","year":"2018","journal-title":"Ther. Adv. Med Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.cell.2016.12.039","article-title":"Understanding the Intersections between Metabolism and Cancer Biology","volume":"168","author":"Heiden","year":"2017","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1158\/1078-0432.CCR-17-3070","article-title":"Oxidative Phosphorylation as an Emerging Target in Cancer Therapy","volume":"24","author":"Ashton","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4187","DOI":"10.1167\/iovs.19-28082","article-title":"Elevated Endogenous SDHA Drives Pathological Metabolism in Highly Metastatic Uveal Melanoma","volume":"60","author":"Chattopadhyay","year":"2019","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6612","DOI":"10.1167\/iovs.14-15202","article-title":"Modeling of Human Uveal Melanoma in Zebrafish Xenograft Embryos","volume":"55","author":"Burrello","year":"2014","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1158\/1541-7786.MCR-17-0007","article-title":"Dysregulated GPCR Signaling and Therapeutic Options in Uveal Melanoma","volume":"15","author":"Chua","year":"2017","journal-title":"Mol. Cancer Res."},{"key":"ref_51","first-page":"757","article-title":"Expression of cysteinyl leukotriene receptors 1 and 2 in uveal melanoma","volume":"60","author":"Goyeneche","year":"2019","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"35033","DOI":"10.18632\/oncotarget.16591","article-title":"A potential anti-tumor effect of leukotriene C4 through the induction of 15-hydroxyprostaglandin dehydrogenase expression in colon cancer cells","volume":"8","author":"Mehdawi","year":"2017","journal-title":"Oncotarget"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"93","DOI":"10.4103\/0301-4738.154367","article-title":"Uveal melanoma: Estimating prognosis","volume":"63","author":"Kaliki","year":"2015","journal-title":"Indian J. Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ceraudo, E., Horioka, M., Mattheisen, J.M., Hitchman, T.D., Moore, A.R., Kazmi, M.A., Chi, P., Chen, Y., Sakmar, T.P., and Huber, T. (2019). Uveal Melanoma Oncogene CYSLTR2 Encodes a Constitutively Active GPCR Highly Biased Toward Gq Signaling. bioRxiv, 663153.","DOI":"10.1101\/663153"},{"key":"ref_55","first-page":"902","article-title":"Montelukast, a cysteinyl leukotriene receptor antagonist, inhibits the growth of chronic myeloid leukemia cells through apoptosis","volume":"40","author":"Zovko","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.canlet.2018.08.019","article-title":"Montelukast, a CysLT1 receptor antagonist, reduces colon cancer stemness and tumor burden in a mouse xenograft model of human colon cancer","volume":"437","author":"Bellamkonda","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Tsai, M.-J., Chang, W.-A., Tsai, P.-H., Wu, C.-Y., Ho, Y.-W., Yen, M.-C., Lin, Y.-S., Kuo, P.-L., and Hsu, Y.-L. (2017). Montelukast Induces Apoptosis-Inducing Factor-Mediated Cell Death of Lung Cancer Cells. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071353"},{"key":"ref_58","first-page":"168","article-title":"Randomised study on adjuvant therapy by DTIC in choroidal melanoma","volume":"12","author":"Desjardins","year":"1998","journal-title":"Ophtalmologie"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/608930","article-title":"Cysteinyl Leukotriene Receptor-1 Antagonists as Modulators of Innate Immune Cell Function","volume":"2014","author":"Theron","year":"2014","journal-title":"J. Immunol. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/j.rmed.2013.06.014","article-title":"Vascular endothelial growth factor and cysteinyl leukotrienes in sputum supernatant of patients with asthma","volume":"107","author":"Papadaki","year":"2013","journal-title":"Respir. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/j.jaci.2004.07.039","article-title":"Cysteinyl leukotriene receptor antagonist regulates vascular permeability by reducing vascular endothelial growth factor expression","volume":"114","author":"Lee","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1378\/chest.125.5.1700","article-title":"Effects of Pranlukast Administration on Vascular Endothelial Growth Factor Levels in Asthmatic Patients","volume":"125","author":"Kanazawa","year":"2004","journal-title":"Chest"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5445","DOI":"10.1167\/iovs.10-5526","article-title":"Inflammatory Cytokines in Eyes with Uveal Melanoma and Relation with Macrophage Infiltration","volume":"51","author":"Ly","year":"2010","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/bjc.2014.342","article-title":"Targeting SRPK1 to control VEGF-mediated tumour angiogenesis in metastatic melanoma","volume":"111","author":"Gammons","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1074\/jbc.M506454200","article-title":"A Single Amino Acid Substitution in the Activation Loop Defines the Decoy Characteristic of VEGFR-1\/FLT-1","volume":"281","author":"Meyer","year":"2006","journal-title":"Journal of Biological Chemistry"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4240","DOI":"10.1167\/iovs.04-0599","article-title":"Expression and Possible Function of IL-2 and IL-15 Receptors on Human Uveal Melanoma Cells","volume":"45","author":"He","year":"2004","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"417a","DOI":"10.1016\/j.bpj.2014.11.2285","article-title":"Chelidonine Interferes with IL-6R\/STAT3 Signaling in Uveal Melanoma Cells","volume":"108","author":"Csomos","year":"2015","journal-title":"Biophys. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1016\/j.ajpath.2020.01.012","article-title":"Oxidative Phosphorylation Promotes Primary Melanoma Invasion","volume":"190","author":"Salhi","year":"2020","journal-title":"Am. J. Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"7037","DOI":"10.1158\/0008-5472.CAN-14-1392","article-title":"Inhibition of mTORC1\/2 Overcomes Resistance to MAPK Pathway Inhibitors Mediated by PGC1 and Oxidative Phosphorylation in Melanoma","volume":"74","author":"Gopal","year":"2014","journal-title":"Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1038\/sj.bjc.6605342","article-title":"\u03b2-Catenin is involved in alterations in mitochondrial activity in non-transformed intestinal epithelial and colon cancer cells","volume":"101","author":"Mezhybovska","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.taap.2006.02.005","article-title":"Control of cellular proliferation by modulation of oxidative phosphorylation in human and rodent fast-growing tumor cells","volume":"215","author":"Vitalgonzalez","year":"2006","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6238","DOI":"10.1158\/0008-5472.CAN-18-3560","article-title":"Comprehensive Benchmarking and Integration of Tumor Microenvironment Cell Estimation Methods","volume":"79","author":"Cast","year":"2019","journal-title":"Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1038\/bjc.2014.417","article-title":"Lack of BAP1 protein expression in uveal melanoma is associated with increased metastatic risk and has utility in routine prognostic testing","volume":"111","author":"Kalirai","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/aja.1002030302","article-title":"Stages of embryonic development of the zebrafish","volume":"203","author":"Kimmel","year":"1995","journal-title":"Dev. Dyn."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1038\/nprot.2010.150","article-title":"Hypoxia-induced metastasis model in embryonic zebrafish","volume":"5","author":"Rouhi","year":"2010","journal-title":"Nat. Protoc."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/10\/2950\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:20:10Z","timestamp":1760178010000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/10\/2950"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,13]]},"references-count":75,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["cancers12102950"],"URL":"https:\/\/doi.org\/10.3390\/cancers12102950","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.08.23.261545","asserted-by":"object"}]},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,13]]}}}