{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:34:55Z","timestamp":1792791295628,"version":"4.5.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["DAMD-OC080179"],"award-info":[{"award-number":["DAMD-OC080179"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Congressionally Directed Medical Research Programs,United States","award":["HT9425-24-1-0193"],"award-info":[{"award-number":["HT9425-24-1-0193"]}],"id":[{"id":"https:\/\/ror.org\/03g2zjp07","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["BX006020"],"award-info":[{"award-number":["BX006020"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ovarian cancer remains one of the deadliest gynecologic cancers globally, with limited progress in early detection and treatment. Syngeneic mouse ovarian cancer cell lines, derived from immunocompetent mice, have become essential tools for studying ovarian cancer biology and assessing novel therapies. With the rise of immunotherapies such as immune checkpoint inhibitors and cancer vaccines, these syngeneic models are critical for preclinical studies within the context of an intact immune system. The availability of diverse syngeneic ovarian cancer models ensures that research captures the full spectrum of human ovarian cancer variability, including variations in genetic mutations, signaling pathways, tumor antigenicity, and molecular subtypes. Here, we report the development and characterization of a panel of syngeneic ovarian cancer cell lines with defined combinations of initiating genetic alterations, such as TP53 deficiency, Hras mutation, and overexpression of Myc and Cyclin E. The Introduction of one or two oncogene drivers resulted in TP53-\/- cell transformation and growth in nude and immunocompetent syngeneic C57BL\/6 mice. Intraperitoneal tumors grew with high penetrance and had a wide metastatic distribution and concurrent ascites, which closely resembles the clinical picture of human serous ovarian cancer.<\/jats:p>","DOI":"10.1038\/s41598-025-18960-5","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T14:23:03Z","timestamp":1759846983000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Immunocompetent C57BL\/6 syngeneic mouse ovarian cancer models with defined genetic alterations"],"prefix":"10.1038","volume":"15","author":[{"given":"Hasmik","family":"Agadjanian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth Y.","family":"Karlan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine S.","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Orsulic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"18960_CR1","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1002\/path.5065","volume":"245","author":"S Stuckelberger","year":"2018","unstructured":"Stuckelberger, S. & Drapkin, R. Precious GEMMs: Emergence of faithful models for ovarian cancer research. J. Pathol. 245, 129\u2013131 (2018).","journal-title":"J. Pathol."},{"key":"18960_CR2","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1038\/s42003-023-05529-z","volume":"6","author":"DP Cook","year":"2023","unstructured":"Cook, D. P. et al. Comparative analysis of syngeneic mouse models of high-grade serous ovarian cancer. Commun. Biol. 6, 1152 (2023).","journal-title":"Commun. Biol."},{"key":"18960_CR3","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1093\/carcin\/21.4.585","volume":"21","author":"KF Roby","year":"2000","unstructured":"Roby, K. F. et al. Development of a syngeneic mouse model for events related to ovarian cancer. Carcinogenesis 21, 585\u2013591 (2000).","journal-title":"Carcinogenesis"},{"key":"18960_CR4","doi-asserted-by":"publisher","first-page":"4219","DOI":"10.3390\/cancers14174219","volume":"14","author":"S Russell","year":"2022","unstructured":"Russell, S. et al. Development and characterization of a luciferase labeled, syngeneic murine model of ovarian cancer. Cancers 14, 4219 (2022).","journal-title":"Cancers"},{"key":"18960_CR5","doi-asserted-by":"publisher","first-page":"16827","DOI":"10.1038\/s41598-017-17119-1","volume":"7","author":"JB Walton","year":"2017","unstructured":"Walton, J. B. et al. CRISPR\/Cas9-derived models of ovarian high grade serous carcinoma targeting Brca1, Pten and Nf1, and correlation with platinum sensitivity. Sci. Rep. 7, 16827 (2017).","journal-title":"Sci. Rep."},{"key":"18960_CR6","doi-asserted-by":"publisher","first-page":"6118","DOI":"10.1158\/0008-5472.CAN-16-1272","volume":"76","author":"J Walton","year":"2016","unstructured":"Walton, J. et al. CRISPR\/Cas9-mediated Trp53 and Brca2 knockout to generate improved murine models of ovarian high-grade serous carcinoma. Cancer Res. 76, 6118\u20136129 (2016).","journal-title":"Cancer Res."},{"key":"18960_CR7","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1073\/pnas.1016538108","volume":"108","author":"MS Goldberg","year":"2011","unstructured":"Goldberg, M. S. et al. Nanoparticle-mediated delivery of siRNA targeting Parp1 extends survival of mice bearing tumors derived from Brca1-deficient ovarian cancer cells. Proc. Natl. Acad. Sci. U S A 108, 745\u2013750 (2011).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"18960_CR8","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1101\/gad.290957.116","volume":"31","author":"SA Yazinski","year":"2017","unstructured":"Yazinski, S. A. et al. ATR inhibition disrupts rewired homologous recombination and fork protection pathways in PARP inhibitor-resistant BRCA-deficient cancer cells. Genes Dev. 31, 318\u2013332 (2017).","journal-title":"Genes Dev."},{"key":"18960_CR9","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/s41698-024-00523-y","volume":"8","author":"Y Hu","year":"2024","unstructured":"Hu, Y. et al. INHBA(+) cancer-associated fibroblasts generate an immunosuppressive tumor microenvironment in ovarian cancer. NPJ Precis. Oncol. 8, 35 (2024).","journal-title":"NPJ Precis. Oncol."},{"key":"18960_CR10","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41551-021-00795-w","volume":"6","author":"J Guo","year":"2022","unstructured":"Guo, J. et al. Cancer vaccines from cryogenically silicified tumour cells functionalized with pathogen-associated molecular patterns. Nat. Biomed. Eng. 6, 19\u201331 (2022).","journal-title":"Nat. Biomed. Eng."},{"key":"18960_CR11","doi-asserted-by":"publisher","first-page":"2528","DOI":"10.1038\/s41467-024-46873-w","volume":"15","author":"L Kasikova","year":"2024","unstructured":"Kasikova, L. et al. Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer. Nat. Commun. 15, 2528 (2024).","journal-title":"Nat. Commun."},{"key":"18960_CR12","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1158\/1078-0432.CCR-24-1594","volume":"31","author":"T Lanickova","year":"2024","unstructured":"Lanickova, T. et al. Chemotherapy drives tertiary lymphoid structures that correlate with ICI-responsive TCF1+CD8+ T cells in metastatic ovarian cancer. Clin. Cancer Res. 31, 164\u2013180 (2024).","journal-title":"Clin. Cancer Res."},{"key":"18960_CR13","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1158\/0008-5472.CAN-15-1382","volume":"76","author":"R Perets","year":"2016","unstructured":"Perets, R. & Drapkin, R. It\u2019s totally tubular riding the new wave of ovarian cancer research. 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