{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:37:08Z","timestamp":1786390628996,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["KYCXJC2025003"],"award-info":[{"award-number":["KYCXJC2025003"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Comparative Oncology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Canine mammary tumours (CMTs) and human breast cancer (HBC) share highly similar pathological characteristics. Cancer stem cells (CSCs) are critical to breast cancer invasion, metastasis, drug resistance, and recurrence. The experiment utilised CMT cell line CMT\u2010U27 and HBC cell line MDA\u2010MB\u2010231. Cancer stem cell spheres were isolated from the two cell lines by serum\u2010free culture respectively, named as CMT\u2010U27 microspheres (CMT\u2010U27S) and MDA\u2010MB\u2010231 microspheres (MDA\u2010MB\u2010231S), and the proportion of CSCs with the CD44\n                    <jats:sup>+<\/jats:sup>\n                    \/CD24\n                    <jats:sup>\u2212<\/jats:sup>\n                    phenotype was identified by flow cytometry. Monensin (MON), one of Polyether ionophore antibiotics, has been demonstrated to effectively suppress various types of CSCs, while erlotinib (ERL), as a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR), effectively inhibits cancer cell growth. This study investigates the synergistic inhibitory effects of MON\u2010ERL combination on CSCs derived from CMTs. Cell viability was analysed by CCK\u20108 assay, while cell invasion and mammosphere formation assays were conducted to evaluate changes. An orthotopic tumour model in nude mice using CMT\u2010U27S was established for in\u00a0vivo validation. The results suggested that MON and ERL combination synergistically inhibited CSCs viability and significantly suppress their invasion and mammosphere formation abilities. The expression of key proteins of the EGFR pathway\u2014\n                    <jats:italic>p<\/jats:italic>\n                    \u2010EGFR, PI3K, and\n                    <jats:italic>p<\/jats:italic>\n                    \u2010AKT was significantly reduced. In animal experiments, tumour volumes in the combination treatment group were markedly reduced compared to those in all other groups (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05), and no lung metastases were observed only in the combination group. Immunofluorescence and immunohistochemistry results indicated a marked reduction of CD44\n                    <jats:sup>+<\/jats:sup>\n                    \/CD24\n                    <jats:sup>\u2212<\/jats:sup>\n                    cells in the combination group, along with suppressed expression of stem cell markers and proliferation\/apoptosis proteins. In conclusion, MON combined with ERL effectively inhibits the proliferation, self\u2010renewal, and metastatic capabilities of CSCs from CMTs by synergistically downregulating the EGFR\/PI3K pathway, demonstrating promising antitumor potential and offering a new strategy for CMTs treatment.\n                  <\/jats:p>","DOI":"10.1111\/vco.70085","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T11:32:44Z","timestamp":1784115164000},"page":"643-656","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhancing\n                    <scp>EGFR<\/scp>\n                    Inhibition: Monensin and Erlotinib Synergize to Eliminate Cancer Stem Cells in Canine Mammary Tumours"],"prefix":"10.1111","volume":"24","author":[{"given":"Tian","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Laboratory Animal Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"},{"name":"The Third Outpatient Department Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"},{"name":"Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, Nanjing Agricultural University  Nanjing China"},{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhao","family":"Song","sequence":"additional","affiliation":[{"name":"Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, Nanjing Agricultural University  Nanjing China"},{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, Nanjing Agricultural University  Nanjing China"},{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8000-8760","authenticated-orcid":false,"given":"Runan","family":"Zuo","sequence":"additional","affiliation":[{"name":"Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, Nanjing Agricultural University  Nanjing China"},{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwei","family":"You","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingfeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Third Outpatient Department Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanxiang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, Nanjing Agricultural University  Nanjing China"},{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawei","family":"Guo","sequence":"additional","affiliation":[{"name":"Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, Nanjing Agricultural University  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