{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T13:40:10Z","timestamp":1782308410444,"version":"3.54.5"},"reference-count":23,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T00:00:00Z","timestamp":1749859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KAKENHI Scientific Research Grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan","award":["22K05996"],"award-info":[{"award-number":["22K05996"]}]},{"name":"KAKENHI Scientific Research Grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan","award":["25K02181"],"award-info":[{"award-number":["25K02181"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Primary pulmonary carcinoma (PC) is a malignant neoplasm that occurs in humans, dogs, and other species. In canine PC, palliative care remains the most practical approach for dogs with inoperable PC. Methods: We investigated the effectiveness of mammalian target of rapamycin (mTOR) inhibitors in canine lung cancer upon PI3K\/AKT\/mTOR activation. Three canine PC cell lines (AZACL1, AZACL2, and cPAC-1) were treated with three mTOR inhibitors (AZD8055, temsirolimus, and everolimus). In vitro, sensitivity assays were conducted to evaluate proliferation and Western blotting was used to examine pathway activation and phosphorylation of mTOR-related protein. Results: AZD8055 had a stronger inhibitory effect on cell proliferation than temsirolimus and everolimus in all three PC cell lines. The IC50 for AZD8055 in the AZACL1, AZACL2, and cPAC-1 cell lines were 23.8 \u03bcM, 95.8 nM, and 237 nM, for temsirolimus they were 34.6 \u03bcM, 11.5 \u03bcM, and 11.2 \u03bcM, and for everolims they were 36.6 \u03bcM, 33.4 \u03bcM, and 33.0 \u03bcM, respectively. Western blotting revealed PI3K\/AKT\/mTOR pathway activation and differential phosphorylation of mTOR signal-related proteins across the three PC cell lines. In xenograft mice injected with the AZACL1 and AZACL2 cell lines we showed that the AZD8055-treated group exhibited a significant reduction in tumor volume via the inhibition of tumor growth compared to the control group. Conclusions: These findings reveal that the PI3K\/AKT\/mTOR pathway plays a key role in canine PC and that AZD8055 may be a novel therapeutic agent for PC-bearing dogs.<\/jats:p>","DOI":"10.3390\/cancers17121991","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T04:06:24Z","timestamp":1750046784000},"page":"1991","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antitumor Effect of mTOR1\/2 Dual Inhibitor AZD8055 in Canine Pulmonary Carcinoma"],"prefix":"10.3390","volume":"17","author":[{"given":"Tomokazu","family":"Nagashima","sequence":"first","affiliation":[{"name":"Department of Veterinary Pathology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5736-0598","authenticated-orcid":false,"given":"Kazuhiko","family":"Ochiai","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Hygiene, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Takizawa","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Oncology, Tokyo University of Agriculture and Technology, Tokyo 183-8538, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youta","family":"Koike","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Oncology, Tokyo University of Agriculture and Technology, Tokyo 183-8538, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Saito","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Oncology, Tokyo University of Agriculture and Technology, Tokyo 183-8538, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asumi","family":"Muramatsu","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daigo","family":"Azakami","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Oncology, Tokyo University of Agriculture and Technology, Tokyo 183-8538, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukino","family":"Machida","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Bonkobara","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Clinical Pathology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Ishiwata","sequence":"additional","affiliation":[{"name":"Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Michishita","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan"},{"name":"One Health One Welfare Center, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rinaldi, V., Finotello, R., Boari, A., Cabibbo, E., and Crisi, P.E. 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