{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T13:47:15Z","timestamp":1770731235180,"version":"3.49.0"},"reference-count":119,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundo Europeu de Desenvolvimento Regional (FEDER) funds","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"Fundo Europeu de Desenvolvimento Regional (FEDER) funds","award":["PRR-09\/C06-834I07\/2024.P11721"],"award-info":[{"award-number":["PRR-09\/C06-834I07\/2024.P11721"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","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 (FCT)","award":["PRR-09\/C06-834I07\/2024.P11721"],"award-info":[{"award-number":["PRR-09\/C06-834I07\/2024.P11721"]}]},{"name":"Faculty of Medicine, University of Porto (FMUP)","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"Faculty of Medicine, University of Porto (FMUP)","award":["PRR-09\/C06-834I07\/2024.P11721"],"award-info":[{"award-number":["PRR-09\/C06-834I07\/2024.P11721"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Future Pharmacology"],"abstract":"<jats:p>Cancer remains a leading cause of mortality worldwide, necessitating innovative therapeutic strategies. Drug repurposing offers a cost-effective approach to cancer treatment by identifying new anticancer applications for existing drugs. Terbutaline, a \u03b22-adrenergic receptor agonist, and Milrinone, a phosphodiesterase-3 inhibitor, are traditionally used as positive inotropic agents but have shown potential anticancer effects. This review explores their mechanisms of action in cancer, focusing on their roles in modulating cyclic adenosine monophosphate (cAMP) levels, oxidative stress, and the tumor microenvironment. Terbutaline influences \u03b22-adrenergic signaling, impacting cell proliferation, angiogenesis, and immune evasion. Milrinone, through PDE3 inhibition, elevates cAMP, promoting apoptosis and reducing tumor growth. Both agents exhibit anti-inflammatory and anti-angiogenic properties, suggesting their potential as adjuvant therapies in oncology. Despite promising preclinical data, clinical validation is required to confirm their efficacy and safety in cancer patients. This review highlights the therapeutic promise of repurposing Terbutaline and Milrinone, emphasizing the need for further research to optimize their application in cancer therapy.<\/jats:p>","DOI":"10.3390\/futurepharmacol5030038","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T13:44:19Z","timestamp":1752241459000},"page":"38","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Repurposing Terbutaline and Milrinone for Cancer Therapy: A Comprehensive Review"],"prefix":"10.3390","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5370-9586","authenticated-orcid":false,"given":"Eduarda","family":"Ribeiro","sequence":"first","affiliation":[{"name":"PerMed Research Group, RISE-Health, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"RISE-Health, 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"PerMed Research Group, RISE-Health, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"RISE-Health, 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"},{"name":"Laboratory of Personalized Medicine, 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":[[2025,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1093\/carcin\/bgp263","article-title":"The global burden of cancer: Priorities for prevention","volume":"31","author":"Thun","year":"2010","journal-title":"Carcinogenesis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.mrrev.2019.04.004","article-title":"The significance of gene mutations across eight major cancer types","volume":"781","author":"Paul","year":"2019","journal-title":"Mutat. 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