{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:31:11Z","timestamp":1786681871600,"version":"build-2736575974"},"reference-count":75,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004612","name":"Funda\u00e7\u00e3o Arauc\u00e1ria","doi-asserted-by":"crossref","award":["029\/2026"],"award-info":[{"award-number":["029\/2026"]}],"id":[{"id":"10.13039\/501100004612","id-type":"DOI","asserted-by":"crossref"}]},{"award":["029\/2026"],"award-info":[{"award-number":["029\/2026"]}],"id":[{"id":"https:\/\/ror.org\/02r7nkw81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background\/Objectives: Melanoma remains one of the most aggressive skin cancers worldwide, with rising incidence and persistent therapeutic challenges, particularly in advanced diseases. Drug repositioning has emerged as a cost- and time-efficient strategy for identifying adjunctive treatments, and antihypertensive medications have attracted attention for their potential off-target antitumor and immunomodulatory effects. This scoping review aimed to map and critically appraise the evidence on the repositioning of antihypertensive drugs for melanoma management. Methods: The review followed the JBI methodology, and the results were reported in accordance with the PRISMA-ScR guidelines. Searches were conducted in July 2025 and updated in May 2026 in PubMed, Scopus, and Web of Science. For Methodological Quality and Risk-of-bias assessment, the SYRCLE Risk of Bias tool was employed for animal studies. Results: This review included 37 studies. \u03b2-Blockers, particularly propranolol, were the most frequently investigated agents (n = 21). Several studies reported antiproliferative, pro-apoptotic, antiangiogenic, and immunomodulatory effects; however, these findings were not uniform. Absent direct antiproliferative effects, biphasic dose responses, lack of angiogenic effects, and outcomes dependent on drug concentration, treatment schedule, and experimental model were also reported. Agents targeting the renin\u2013angiotensin system and calcium channels similarly produced heterogeneous and context-dependent findings. The animal studies frequently presented high or unclear risk of bias, particularly because of incomplete reporting of randomization, allocation concealment, and blinding. No formal methodological quality assessment was performed for the in vitro studies. Conclusions: Antihypertensive agents, particularly \u03b2-blockers, show promising but heterogeneous preclinical signals in melanoma. However, the available evidence is not sufficient to establish reproducible efficacy or translational validity. Standardized and methodologically rigorous preclinical studies are required before these agents can be considered for clinical investigation as adjunctive melanoma therapies.<\/jats:p>","DOI":"10.3390\/diseases14080291","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T09:11:36Z","timestamp":1786525896000},"page":"291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antihypertensive Drugs as Potential Repositioning Options for Melanoma: A Map of Pre-Clinical Evidence"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6426-6186","authenticated-orcid":false,"given":"Naomi Gerzvolf","family":"Mieres","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal do Paran\u00e1, Curitiba 80210-170, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kauanna","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal do Paran\u00e1, Curitiba 80210-170, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7576-406X","authenticated-orcid":false,"given":"Nath\u00e1lia Carolina Barreiro","family":"Marques","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal do Paran\u00e1, Curitiba 80210-170, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3327-2884","authenticated-orcid":false,"given":"Nicole Milagritos Cardoso","family":"Azorza","sequence":"additional","affiliation":[{"name":"Carrera de Farmacia y Bioqu\u00edmica, Facultad de Ciencias de la Salud, Universidad Cient\u00edfica del Sur, Villa El Salvador, Lima 15023, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9723-584X","authenticated-orcid":false,"given":"Helena Hiemisch Lobo","family":"Borba","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal do Paran\u00e1, Curitiba 80210-170, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7049-4363","authenticated-orcid":false,"given":"Roberto","family":"Pontarolo","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal do Paran\u00e1, Curitiba 80210-170, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9913-9306","authenticated-orcid":false,"given":"Marcel Henrique Marcondes","family":"Sari","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal do Paran\u00e1, Curitiba 80210-170, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Sartori","family":"Bonini","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Departamento de Farm\u00e1cia, Universidade Estadual do Centro-Oeste, Guarapuava 85040-167, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7388-8256","authenticated-orcid":false,"given":"J\u00e9ssica Brand\u00e3o","family":"Reolon","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Departamento de Farm\u00e1cia, Universidade Estadual do Centro-Oeste, Guarapuava 85040-167, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3434-1239","authenticated-orcid":false,"given":"Raul Edison Luna","family":"Lazo","sequence":"additional","affiliation":[{"name":"Carrera de Farmacia y Bioqu\u00edmica, Facultad de Ciencias de la Salud, Universidad Cient\u00edfica del Sur, Villa El Salvador, Lima 15023, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9951-587X","authenticated-orcid":false,"given":"Luana Mota","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal do Paran\u00e1, Curitiba 80210-170, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1136\/jclinpath-2013-201471","article-title":"Molecular Biology of Normal Melanocytes and Melanoma Cells","volume":"66","author":"Bandarchi","year":"2013","journal-title":"J. Clin. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.23736\/S2784-8671.24.07811-3","article-title":"Melanoma Epidemiology in Europe: What Is New?","volume":"159","author":"Nurla","year":"2024","journal-title":"Ital. J. Dermatol. Venereol."},{"key":"ref_3","unstructured":"(2026, August 09). Instituto Nacional de C\u00e2ncer\u2014INCA, Available online: https:\/\/www.Gov.Br\/Inca\/Pt-Br."},{"key":"ref_4","unstructured":"(2026, August 09). Melanoma Cut\u00e2neo (DDT)\u2014Minist\u00e9rio Da Sa\u00fade [Internet], Available online: https:\/\/www.Gov.Br\/Saude\/Pt-Br\/Assuntos\/Pcdt\/m\/Melanoma-Cutaneo-Ddt\/View."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1634\/theoncologist.2010-0190","article-title":"Systematic Review of Medical Treatment in Melanoma: Current Status and Future Prospects","volume":"16","author":"Garbe","year":"2011","journal-title":"Oncologist"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1158\/2159-8290.CD-20-1680","article-title":"The Next Decade of Immune Checkpoint Therapy","volume":"11","author":"Sharma","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"172784","DOI":"10.1016\/j.ejphar.2019.172784","article-title":"Old Wine in New Bottles: Drug Repurposing in Oncology","volume":"866","author":"Antoszczak","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Cort\u00e9s, H., Reyes-Hern\u00e1ndez, O.D., Alcal\u00e1-Alcal\u00e1, S., Bernal-Ch\u00e1vez, S.A., Caballero-Flor\u00e1n, I.H., Gonz\u00e1lez-Torres, M., Sharifi-Rad, J., Gonz\u00e1lez-Del Carmen, M., Figueroa-Gonz\u00e1lez, G., and Leyva-G\u00f3mez, G. (2021). Repurposing of Drug Candidates for Treatment of Skin Cancer. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.605714"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Fateeva, A., Eddy, K., and Chen, S. (2024). Current State of Melanoma Therapy and Next Steps: Battling Therapeutic Resistance. Cancers, 16.","DOI":"10.3390\/cancers16081571"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrd.2018.168","article-title":"Drug Repurposing: Progress, Challenges and Recommendations","volume":"18","author":"Pushpakom","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.trecan.2017.06.007","article-title":"Repurposing Drugs in Oncology: Next Steps","volume":"3","author":"Verbaanderd","year":"2017","journal-title":"Trends Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Carlos-Escalante, J.A., de Jes\u00fas-S\u00e1nchez, M., Rivas-Castro, A., Pichardo-Rojas, P.S., Arce, C., and Wegman-Ostrosky, T. (2021). The Use of Antihypertensive Drugs as Coadjuvant Therapy in Cancer. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.660943"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.phrs.2017.07.026","article-title":"Antihypertensive Drugs","volume":"124","author":"Laurent","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1177\/1470320313496858","article-title":"The Renin-Angiotensin System Meets the Hallmarks of Cancer","volume":"16","year":"2015","journal-title":"J. Renin. Angiotensin. Aldosterone. Syst."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1111\/pcmr.12918","article-title":"Antihypertensives and Melanoma: An Updated Review","volume":"33","author":"Williams","year":"2020","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41392-024-01808-1","article-title":"Drug Repurposing for Cancer Therapy","volume":"9","author":"Xia","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ribeiro Cavalcante, B.R., Freitas, R.D., de Oliveira Siquara da Rocha, L., Rocha, G.V., de Carvalho Pach\u00eaco, T.C., Pereira Ramos, P.I., and Gurgel Rocha, C.A. (2022). In Silico Approaches for Drug Repurposing in Oncology: Protocol for a Scoping Review of Existing Evidence. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0271002"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"du Sert, N.P., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE Guidelines 2.0: Updated Guidelines for Reporting Animal Research. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000410"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1097\/XEB.0000000000000050","article-title":"Guidance for Conducting Systematic Scoping Reviews","volume":"13","author":"Peters","year":"2015","journal-title":"Int. J. Evid. Based. Healthc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"467","DOI":"10.7326\/M18-0850","article-title":"PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation","volume":"169","author":"Tricco","year":"2018","journal-title":"Ann. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13643-016-0384-4","article-title":"Rayyan\u2014A Web and Mobile App for Systematic Reviews","volume":"5","author":"Ouzzani","year":"2016","journal-title":"Syst. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e8164","DOI":"10.5867\/medwave.2021.03.8164","article-title":"Graphical Representation of the Body of the Evidence: The Essentials for Understanding the Evidence Gap Map Approach","volume":"21","author":"Meza","year":"2021","journal-title":"Medwave"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Machado, P., Ribeiro, F.N., Giublin, F.C.W., Mieres, N.G., Tonin, F.S., Pontarolo, R., Sari, M.H.M., Lazo, R.E.L., and Ferreira, L.M. (2025). Next-Generation Wound Care: A Scoping Review on Probiotic, Prebiotic, Synbiotic, and Postbiotic Cutaneous Formulations. Pharmaceuticals, 18.","DOI":"10.3390\/ph18050704"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hooijmans, C.R., Rovers, M.M., De Vries, R.B.M., Leenaars, M., Ritskes-Hoitinga, M., and Langendam, M.W. (2014). SYRCLE\u2019s Risk of Bias Tool for Animal Studies. BMC Med. Res. Methodol., 14.","DOI":"10.1186\/1471-2288-14-43"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7265","DOI":"10.1002\/cam4.2594","article-title":"Beta-Blockers Exert Potent Anti-Tumor Effects in Cutaneous and Uveal Melanoma","volume":"8","author":"Bustamante","year":"2019","journal-title":"Cancer Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1111\/bph.14660","article-title":"\u03923-Adrenoceptor as a Potential Immuno-Suppressor Agent in Melanoma","volume":"176","author":"Calvani","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"De Alvarenga, E.C., De Castro Fonseca, M., Carvalho, C.C., Florentino, R.M., Fran\u00e7a, A., Matias, E., Guimar\u00e3es, P.B., Batista, C., Freire, V., and Carmona, A.K. (2016). Angiotensin Converting Enzyme Regulates Cell Proliferation and Migration. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165371"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1002\/ijc.20400","article-title":"Anti-Tumor Activity of a Combination of Plasminogen Activator and Captopril in a Human Melanoma Xenograft Model","volume":"112","author":"Ruers","year":"2004","journal-title":"Int. J. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.4049\/jimmunol.0903301","article-title":"Improving Survival Rates in Two Models of Spontaneous Postoperative Metastasis in Mice by Combined Administration of a Beta-Adrenergic Antagonist and a Cyclooxygenase-2 Inhibitor","volume":"184","author":"Glasner","year":"2010","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"247","DOI":"10.20892\/j.issn.2095-3941.2018.0375","article-title":"Telmisartan Induces Melanoma Cell Apoptosis and Synergizes with Vemurafenib in Vitro by Altering Cell Bioenergetics","volume":"16","author":"Grahovac","year":"2019","journal-title":"Cancer Biol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1111\/j.1349-7006.2002.tb01313.x","article-title":"Psychosocial Stress Augments Tumor Development through Beta-Adrenergic Activation in Mice","volume":"93","author":"Hasegawa","year":"2002","journal-title":"Jpn. J. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.4049\/jimmunol.2100719","article-title":"The Sympathetic Nervous System Modulates Cancer Vaccine Activity through Monocyte-Derived Cells","volume":"207","author":"Hinkle","year":"2021","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e1405205","DOI":"10.1080\/2162402X.2017.1405205","article-title":"Beta Blocker Use Correlates with Better Overall Survival in Metastatic Melanoma Patients and Improves the Efficacy of Immunotherapies in Mice","volume":"7","author":"Kokolus","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"802","DOI":"10.18632\/oncotarget.22696","article-title":"Propranolol Enhanced the Anti-Tumor Effect of Sunitinib by Inhibiting Proliferation and Inducing G0\/G1\/S Phase Arrest in Malignant Melanoma","volume":"9","author":"Kuang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/bph.13662","article-title":"Biphasic Effects of Propranolol on Tumour Growth in B16F10 Melanoma-Bearing Mice","volume":"174","author":"Maccari","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Matarrese, P., Maccari, S., Ascione, B., Vona, R., Vezzi, V., Stati, T., Gr\u00f2, M.C., Marano, G., Ambrosio, C., and Molinari, P. (2022). Crosstalk between \u03922- and A2-Adrenergic Receptors in the Regulation of B16F10 Melanoma Cell Proliferation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094634"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Mieres, N.G., Simi\u00e3o, S.d.O., Cruz, L.S., Melo, R.C.d., Khalil, N.M., Bonini, J.S., Rego, F.G.d.M., Sari, M.H.M., Pontarolo, R., and Lazo, R.E.L. (2025). Bioadhesive Eudragit RL\u00ae 100 Nanocapsules for Melanoma Therapy: A Repurposing Strategy for Propranolol. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17060718"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ccell.2018.12.001","article-title":"An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles","volume":"35","author":"Ortiz","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00280-009-1136-0","article-title":"Inhibition of Angiotensin II Receptor 1 Limits Tumor-Associated Angiogenesis and Attenuates Growth of Murine Melanoma","volume":"66","author":"Otake","year":"2010","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1038\/s41388-018-0563-y","article-title":"The Renin Angiotensin System (RAS) Mediates Bifunctional Growth Regulation in Melanoma and Is a Novel Target for Therapeutic Intervention","volume":"38","author":"Renziehausen","year":"2019","journal-title":"Oncogene"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1158\/1940-6207.CAPR-19-0370","article-title":"Stress-Induced Norepinephrine Downregulates CCL2 in Macrophages to Suppress Tumor Growth in a Model of Malignant Melanoma","volume":"13","author":"Steinberger","year":"2020","journal-title":"Cancer Prev. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1016\/j.jsps.2023.05.020","article-title":"In Vitro and in Silico Study on the Effect of Carvedilol and Sorafenib Alone and in Combination on the Growth and Inflammatory Response of Melanoma Cells","volume":"31","author":"Wawszczyk","year":"2023","journal-title":"Saudi Pharm. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1600-0749.1991.tb00445.x","article-title":"Inhibition of Tumor Cell Invasion by Verapamil","volume":"4","author":"Yohem","year":"1991","journal-title":"Pigment Cell Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1097\/CAD.0000000000001597","article-title":"Nebivolol, an Antihypertensive Agent, Has New Application in Inhibiting Melanoma","volume":"35","author":"Yang","year":"2024","journal-title":"Anti-Cancer Drugs"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4095","DOI":"10.1158\/1078-0432.CCR-05-2489","article-title":"Captopril, an Angiotensin-Converting Enzyme Inhibitor, Promotes Growth of Immunogenic Tumors in Mice","volume":"12","author":"Wysocki","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/jid.2014.373","article-title":"Inhibition of Human Melanoma Growth by a Non-Cardioselective \u03b2-Blocker","volume":"135","author":"Wrobel","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"77825","DOI":"10.18632\/oncotarget.12833","article-title":"Le Propranolol Induces a Favourable Shift of Anti-Tumor Immunity in a Murine Spontaneous Model of Melanoma","volume":"7","author":"Wrobel","year":"2016","journal-title":"Oncotarget"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"68314","DOI":"10.18632\/oncotarget.11599","article-title":"Propranolol Induced G0\/G1\/S Phase Arrest and Apoptosis in Melanoma Cells via AKT\/MAPK Pathway","volume":"7","author":"Zhou","year":"2016","journal-title":"Oncotarget"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e21200428","DOI":"10.1590\/1678-4324-2021200428","article-title":"Evaluation of Depressive and Anxious Behavior with the Use of Propranolol in Melanoma-Bearing Mice","volume":"64","author":"Berton","year":"2021","journal-title":"Braz. Arch. Biol. Technol."},{"key":"ref_50","first-page":"457","article-title":"The ACE Inhibitor Lisinopril Stimulates Melanoma Cell Invasiveness by Inducing MMP2 Secretion","volume":"56","author":"Becker","year":"2022","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1097\/00008390-199310000-00008","article-title":"The Ca2+ Channel Blocker Verapamil Enhances Melanogenesis without Altering Metastatic Potential in the B16 Murine Melanoma","volume":"3","author":"Parker","year":"1993","journal-title":"Melanoma Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/j.1755-148X.2012.00978.x","article-title":"Functional Expression of Voltage-Gated Calcium Channels in Human Melanoma","volume":"25","author":"Das","year":"2012","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1111\/pcmr.12155","article-title":"T-Type Calcium Channel Blockers Inhibit Autophagy and Promote Apoptosis of Malignant Melanoma Cells","volume":"26","author":"Das","year":"2013","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1007\/s00109-013-1073-6","article-title":"Functional Involvement of \u03923-Adrenergic Receptors in Melanoma Growth and Vascularization","volume":"91","author":"Casini","year":"2013","journal-title":"J. Mol. Med."},{"key":"ref_55","first-page":"1090","article-title":"Selective Uveal Melanoma Inhibition with Calcium Channel Blockade","volume":"55","author":"Shaughnessy","year":"2019","journal-title":"Int. J. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/bjc.1988.79","article-title":"Verapamil Potentiation of Doxorubicin Resistance Development in B16 Melanoma Cells Both in Vitro and in Vivo","volume":"57","author":"Formelli","year":"1988","journal-title":"Br. J. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Rama, L., Almeida, M., Jose, J., Pereira, M.d.L., and Oliveira, M. (2025). Beta-Blockers as Potential Adjuvants in Melanoma Treatment. Toxics, 13.","DOI":"10.3390\/toxics13110981"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"He, Y., Liu, H., Hendgen-Cotta, U., Rassaf, T., Bechrakis, N.E., and Berchner-Pfannschmidt, U. (2025). The Discovery of \u03b1-Adrenoceptor Antagonists as a Potential New Treatment Option for Uveal Melanoma. Biomolecules, 15.","DOI":"10.3390\/biom15101436"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Vukadinovi\u0107, D., Damjanovi\u0107, A., Vukovi\u0107, M., \u010cudina, O., Grahovac, J., and Dobri\u010di\u0107, V. (2025). Newly Synthesized Telmisartan\u2013Amino Acid Conjugates Exhibit Enhanced Cytotoxic Effects in Malignant Melanoma Cells. Molecules, 31.","DOI":"10.3390\/molecules31010125"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10063","DOI":"10.1038\/s41467-025-65048-9","article-title":"\u03b2-Adrenergic Signaling Blockade Attenuates Metastasis through Activation of Cytotoxic CD4 T Cells","volume":"16","author":"Johansen","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e011611","DOI":"10.1136\/jitc-2025-011611","article-title":"ADRB2 Inhibition Suppresses Cancer Immune Evasion by Regulating Tumor SOX10-PD-L1 Axis and T Cell Function","volume":"13","author":"Zhang","year":"2025","journal-title":"J. Immunother. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1002\/cpt.1846","article-title":"Does In Vitro Potency Predict Clinically Efficacious Concentrations?","volume":"108","author":"Hjorth","year":"2020","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41392-023-01481-w","article-title":"The Blood-Brain Barrier: Structure, Regulation, and Drug Delivery","volume":"8","author":"Wu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1586\/era.12.118","article-title":"\u03b2-Adrenergic-Blocking Drugs and Melanoma: Current State of the Art","volume":"12","author":"Grazzini","year":"2012","journal-title":"Expert Rev. Anti-Cancer Ther."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Wrobel, L.J., Gayet-Ageron, A., and Gal, F.A. (2020). Le Effects of Beta-Blockers on Melanoma Microenvironment and Disease Survival in Human. Cancers, 12.","DOI":"10.3390\/cancers12051094"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Spitschak, A., Gupta, S., Singh, K.P., Logotheti, S., and P\u00fctzer, B.M. (2022). Drug Repurposing at the Interface of Melanoma Immunotherapy and Autoimmune Disease. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010083"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1007\/s40471-019-00192-7","article-title":"Sex Differences in Melanoma","volume":"6","author":"Schwartz","year":"2019","journal-title":"Curr. Epidemiol. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s11906-022-01183-8","article-title":"Sex Differences in the Prevalence, Outcomes and Management of Hypertension","volume":"24","author":"Connelly","year":"2022","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/s41371-023-00801-5","article-title":"Hypertension: Sex-Related Differences in Drug Treatment, Prevalence and Blood Pressure Control in Primary Care","volume":"37","author":"Bager","year":"2023","journal-title":"J. Hum. Hypertens."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/S1470-2045(18)30261-4","article-title":"Cancer Immunotherapy Efficacy and Patients\u2019 Sex: A Systematic Review and Meta-Analysis","volume":"19","author":"Conforti","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1001\/jamaoncol.2018.5904","article-title":"Association of Patient Sex With Efficacy of Immune Checkpoint Inhibitors and Overall Survival in Advanced Cancers","volume":"5","author":"Wallis","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"15413","DOI":"10.18632\/aging.203100","article-title":"Sex-Related Differences in the Efficacy of Immune Checkpoint Inhibitors in Malignancy: A Systematic Review and Meta-Analysis","volume":"13","author":"Lai","year":"2021","journal-title":"Aging"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Karp, N.A., Pearl, E.J., Stringer, E.J., Barkus, C., Ulrichsen, J.C., and Percie du Sert, N. (2022). A Qualitative Study of the Barriers to Using Blinding in in Vivo Experiments and Suggestions for Improvement. PLoS Biol., 20.","DOI":"10.1371\/journal.pbio.3001873"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/jrsm.1411","article-title":"Risk-of-Bias VISualization (Robvis): An R Package and Shiny Web App for Visualizing Risk-of-Bias Assessments","volume":"12","author":"McGuinness","year":"2021","journal-title":"Res. Synth. Methods"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/s00432-025-06262-2","article-title":"Does Propranolol Have a Role in Cancer Treatment? A Systematic Review of the Epidemiological and Clinical Trial Literature on Beta-Blockers","volume":"151","author":"Tarantola","year":"2025","journal-title":"J. Cancer Res. Clin. Oncol."}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/8\/291\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:23:50Z","timestamp":1786681430000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/8\/291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":75,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["diseases14080291"],"URL":"https:\/\/doi.org\/10.3390\/diseases14080291","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]}}}