{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:44:18Z","timestamp":1788381858695,"version":"build-2803163510"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":36,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ir Vet J"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Osteosarcoma (OSA) is the most common and aggressive primary bone tumor in dogs. OSA frequently metastasizes to the lungs and has a poor prognosis despite current standard treatment. This case report described the clinical course of a 3-year-old castrated male Jindo dog diagnosed with right tibial OSA and a pre-existing pulmonary metastasis. Initially, the patient received adjuvant chemotherapy and maintained a stable disease state for approximately five months (21 weeks from initial diagnosis) until radiographic and computed tomography (CT) examinations revealed progressive pulmonary metastasis.<\/jats:p>\n                  <jats:p>In response to this progression, the treatment was shifted to a triple-combination regimen of carboplatin, high-dose losartan (angiotensin II type 1 receptor blocker [ARB], 10\u00a0mg\/kg PO BID), and toceranib (2.75\u00a0mg\/kg PO EOD). Nine weeks (30 weeks from diagnosis) after initiating this new regimen, a comprehensive CT re-evaluation demonstrated a significant positive response, marked by the radiographic disappearance of pulmonary nodules and complete resolution of the pleural effusion. This substantial improvement indicated a potential clinical benefit of the triple-combination regimen, which may suggest a synergistic effect when used alongside concurrent carboplatin cycles, in addition to losartan\u2019s proposed capacity to remodel the tumor microenvironment (TME) and enhance toceranib efficacy. However, following the conclusion of the carboplatin cycles at week 30, the patient\u2019s condition ultimately deteriorated despite the continuation of losartan and toceranib combination therapy, confirming extensive disease progression by week 40. A subsequent attempt with doxorubicin as a third-line agent resulted in severe adverse effects, including bone marrow suppression and life-threatening neutropenia, leading to the patient\u2019s death shortly thereafter (43 weeks from diagnosis).<\/jats:p>\n                  <jats:p>This case presents a notable clinical observation of a favorable short-term response of high-dose losartan in combination with toceranib for progressive pulmonary metastatic OSA, potentially through favorable TME modulation. It also highlighted the inherent virulence of canine OSA and the challenges in achieving sustained long-term control. The development of innovative multimodal therapeutic approaches for the management of canine OSA is critically important.<\/jats:p>","DOI":"10.1186\/s13620-026-00337-3","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T07:54:20Z","timestamp":1772438060000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Losartan, toceranib, and carboplatin combination therapy for progressive pulmonary metastasis in canine osteosarcoma: a case report"],"prefix":"10.1186","volume":"79","author":[{"given":"Ji-Hoon","family":"Kwak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Nyun","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu-Shik","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"issue":"2","key":"337_CR1","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1111\/vco.13041","volume":"23","author":"S Zanardi","year":"2025","unstructured":"Zanardi S, Sabattini S, Rossi F, et al. Adjuvant Chemotherapy Is Associated With Prolonged Survival Time in Small-Breed Dogs Undergoing Amputation for Appendicular Osteosarcoma. Vet Comp Oncol. 2025;23(2):161\u20137. https:\/\/doi.org\/10.1111\/vco.13041.","journal-title":"Vet Comp Oncol"},{"issue":"3","key":"337_CR2","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.tvjl.2010.08.014","volume":"189","author":"E Morello","year":"2011","unstructured":"Morello E, Martano M, Buracco P. Biology, diagnosis and treatment of canine appendicular osteosarcoma: similarities and differences with human osteosarcoma. Vet J. 2011;189(3):268\u201377. https:\/\/doi.org\/10.1016\/j.tvjl.2010.08.014.","journal-title":"Vet J"},{"issue":"11","key":"337_CR3","doi-asserted-by":"publisher","first-page":"5152","DOI":"10.3390\/ijms26115152","volume":"26","author":"A Dolnicka","year":"2025","unstructured":"Dolnicka A, Fosse V, Raciborska A, \u015amieszek A. Building a Therapeutic Bridge Between Dogs and Humans: A Review of Potential Cross-Species Osteosarcoma Biomarkers. Int J Mol Sci. 2025;26(11):5152. https:\/\/doi.org\/10.3390\/ijms26115152.","journal-title":"Int J Mol Sci"},{"issue":"3","key":"337_CR4","first-page":"301","volume":"61","author":"AC Poon","year":"2020","unstructured":"Poon AC, Matsuyama A, Mutsaers AJ. Recent and current clinical trials in canine appendicular osteosarcoma. Can Vet J. 2020;61(3):301\u20138.","journal-title":"Can Vet J"},{"issue":"12","key":"337_CR5","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.2460\/javma.228.12.1905","volume":"228","author":"SE Boston","year":"2006","unstructured":"Boston SE, Ehrhart NP, Dernell WS, Lafferty M, Withrow SJ. Evaluation of survival time in dogs with stage III osteosarcoma that undergo treatment: 90 cases (1985\u20132004). J Am Vet Med Assoc. 2006;228(12):1905\u20138. https:\/\/doi.org\/10.2460\/javma.228.12.1905.","journal-title":"J Am Vet Med Assoc"},{"issue":"11","key":"337_CR6","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.2460\/javma.251.11.1293","volume":"251","author":"H Turner","year":"2017","unstructured":"Turner H, S\u00e9guin B, Worley DR, et al. Prognosis for dogs with stage III osteosarcoma following treatment with amputation and chemotherapy with and without metastasectomy. J Am Vet Med Assoc. 2017;251(11):1293\u2013305. https:\/\/doi.org\/10.2460\/javma.251.11.1293.","journal-title":"J Am Vet Med Assoc"},{"issue":"4","key":"337_CR7","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1158\/1078-0432.CCR-21-2105","volume":"28","author":"DP Regan","year":"2022","unstructured":"Regan DP, Chow L, Das S, et al. Losartan Blocks Osteosarcoma-Elicited Monocyte Recruitment, and Combined With the Kinase Inhibitor Toceranib, Exerts Significant Clinical Benefit in Canine Metastatic Osteosarcoma. Clin Cancer Res. 2022;28(4):662\u201376. https:\/\/doi.org\/10.1158\/1078-0432.CCR-21-2105.","journal-title":"Clin Cancer Res"},{"issue":"8","key":"337_CR8","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1292\/jvms.23-0204","volume":"85","author":"S Maeda","year":"2023","unstructured":"Maeda S. Second era of molecular-targeted cancer therapies in dogs. J Vet Med Sci. 2023;85(8):790\u20138. https:\/\/doi.org\/10.1292\/jvms.23-0204.","journal-title":"J Vet Med Sci"},{"issue":"4","key":"337_CR9","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1158\/1078-0432.CCR-21-3471","volume":"28","author":"MC Weiss","year":"2022","unstructured":"Weiss MC, Eulo V, Van Tine BA. Truly Man\u2019s Best Friend: Canine Cancers Drive Drug Repurposing in Osteosarcoma. Clin Cancer Res. 2022;28(4):571\u20132. https:\/\/doi.org\/10.1158\/1078-0432.CCR-21-3471.","journal-title":"Clin Cancer Res"},{"issue":"4","key":"337_CR10","doi-asserted-by":"publisher","first-page":"e0124889","DOI":"10.1371\/journal.pone.0124889","volume":"10","author":"CA London","year":"2015","unstructured":"London CA, Gardner HL, Mathie T, et al. Impact of Toceranib\/Piroxicam\/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study. PLoS ONE. 2015;10(4):e0124889. https:\/\/doi.org\/10.1371\/journal.pone.0124889. Published 2015 Apr 29.","journal-title":"PLoS ONE"},{"issue":"11","key":"337_CR11","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.2460\/javma.252.11.1377","volume":"252","author":"A Matsuyama","year":"2018","unstructured":"Matsuyama A, Schott CR, Wood GA, Richardson D, Woods JP, Mutsaers AJ. Evaluation of metronomic cyclophosphamide chemotherapy as maintenance treatment for dogs with appendicular osteosarcoma following limb amputation and carboplatin chemotherapy. J Am Vet Med Assoc. 2018;252(11):1377\u201383. https:\/\/doi.org\/10.2460\/javma.252.11.1377.","journal-title":"J Am Vet Med Assoc"},{"key":"337_CR12","doi-asserted-by":"publisher","first-page":"1394284","DOI":"10.3389\/fimmu.2024.1394284","volume":"15","author":"S Orrapin","year":"2024","unstructured":"Orrapin S, Moonmuang S, Udomruk S, Yongpitakwattana P, Pruksakorn D, Chaiyawat P. Unlocking the tumor-immune microenvironment in osteosarcoma: insights into the immune landscape and mechanisms. Front Immunol. 2024;15:1394284. https:\/\/doi.org\/10.3389\/fimmu.2024.1394284.","journal-title":"Front Immunol"},{"key":"337_CR13","doi-asserted-by":"publisher","first-page":"660943","DOI":"10.3389\/fonc.2021.660943","volume":"11","author":"JA Carlos-Escalante","year":"2021","unstructured":"Carlos-Escalante JA, de Jes\u00fas-S\u00e1nchez M, Rivas-Castro A, Pichardo-Rojas PS, Arce C, Wegman-Ostrosky T. The Use of Antihypertensive Drugs as Coadjuvant Therapy in Cancer. Front Oncol. 2021;11:660943. https:\/\/doi.org\/10.3389\/fonc.2021.660943.","journal-title":"Front Oncol"}],"container-title":["Irish Veterinary Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13620-026-00337-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13620-026-00337-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13620-026-00337-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T19:08:19Z","timestamp":1781636899000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13620-026-00337-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,2]]},"references-count":13,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["337"],"URL":"https:\/\/doi.org\/10.1186\/s13620-026-00337-3","relation":{},"ISSN":["2046-0481"],"issn-type":[{"value":"2046-0481","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,2]]},"assertion":[{"value":"20 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written consent was obtained from the patient\u2019s owner.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20"}}