{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T09:19:28Z","timestamp":1789463968107,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K02574"],"award-info":[{"award-number":["24K02574"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K24653"],"award-info":[{"award-number":["25K24653"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K12471"],"award-info":[{"award-number":["25K12471"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K18360"],"award-info":[{"award-number":["25K18360"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26K12115"],"award-info":[{"award-number":["26K12115"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP266f0137009j0002"],"award-info":[{"award-number":["JP266f0137009j0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Canines share close environmental and physiological homologies with humans, making them essential large\u2010animal models in preclinical drug discovery. However, species\u2010specific discrepancies in therapeutic responsiveness often limit the direct extrapolation of canine data to human clinical scenarios. Although osteosarcoma (OS) spontaneously occurs in large\u2010breed dogs at an incidence 30\u2010fold higher than in humans, the underlying interspecies molecular differences governing tumor behavior and drug sensitivity remain poorly understood. This study aimed to systematically evaluate the translational reliability and limitations of the canine OS model by comparing human and canine malignant architectures at baseline and during anti\u2010cancer drug exposure. By integrating single\u2010cell RNA sequencing (scRNA\u2010seq) from treatment\u2010naive patient specimens with multi\u2010conditional temporal bulk RNA\u2010seq of representative cell lines, we interrogated their dynamic transcriptomic responses to Trabectedin. Integrated single\u2010cell analysis revealed that human OS possesses a highly primitive, high\u2010stemness subpopulation hierarchy and a more primed tumor\u2010infiltrating lymphocyte (TIL) profile than canine OS. Pharmacogenomic assays demonstrated that these distinct cellular architectures dictate therapeutic vulnerabilities: The rigid, high\u2010stemness hierarchy of human OS facilitates transcriptomic robustness and adaptive drug resistance. In contrast, the fluid, less primitive network of canine OS renders its tumor cells prone to immediate, stochastically driven functional network collapse and superior Trabectedin sensitivity. Collectively, our study provides a comprehensive comparative molecular framework for human and canine OS. These findings emphasize the necessity of accounting for species\u2010specific stemness and immune landscapes, ultimately accelerating the precision development of next\u2010generation OS therapeutics.<\/jats:p>","DOI":"10.1111\/cas.70524","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:30:19Z","timestamp":1789122619000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Transcriptomics of Human and Canine Osteosarcoma Reveals Species Stemness and Trabectedin Sensitivity"],"prefix":"10.1111","author":[{"given":"Kenta","family":"Kono","sequence":"first","affiliation":[{"name":"Division of Rare Cancer Research National Cancer Center Research Institute  Tokyo Japan"},{"name":"Department of Orthopaedic Surgery, Graduate School of Medicine Chiba University  Chiba 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