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Mouse models of epithelial ovarian cancer for preclinical studies

Sergey Karakashev Ru-Gang Zhang

Sergey Karakashev, Ru-Gang Zhang. Mouse models of epithelial ovarian cancer for preclinical studies. Zoological Research, 2021, 42(2): 153-160. doi: 10.24272/j.issn.2095-8137.2020.382
Citation: Sergey Karakashev, Ru-Gang Zhang. Mouse models of epithelial ovarian cancer for preclinical studies. Zoological Research, 2021, 42(2): 153-160. doi: 10.24272/j.issn.2095-8137.2020.382

卵巢癌临床前小鼠模型

doi: 10.24272/j.issn.2095-8137.2020.382

Mouse models of epithelial ovarian cancer for preclinical studies

Funds: This work was supported by the US National Institutes of Health (R01CA160331, R01CA163377, R01CA202919, R01CA239128, P01AG031862, P50CA228991 to R.G.Z. and K99CA241395 to S.K.), US Department of Defense (OC180109 and OC190181 to R.G.Z.). The Honorable Tina Brozman Foundation for Ovarian Cancer Research (to R.G.Z.), and Ovarian Cancer Research Alliance Collaborative Research Development Grant (to R.G.Z.). Core facilities support was provided by a Cancer Centre Support Grant (CA010815) to the Wistar Institute
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  • 摘要: 在发达国家,上皮性卵巢癌仍然是最致命的妇科肿瘤,研发新的卵巢癌治疗策略对战胜这一疾病具有重要意义。根据组织、 分子和遗传差异,上皮性卵巢癌可分为多种亚型。在研发新的卵巢癌治疗策略的研究中,使用临床疾病相关的临床前动物模型对转化相关研究成果至关重要。我们总结了相关卵巢癌临床前小鼠模型的新进展并探讨了不同小鼠模型的优缺点。
  • Table  1.   Classification of EOC mouse models based on injection site

    AdvantagesDisadvantages
    Subcutaneous model
    √ Easy to perform√ Model is not physiologically relevant
    √ Suitable for monitoring tumor growth√ Absence of tumor microenvironment
    √ Low variability in tumor size√ Not suitable for studying angiogenesis
    √ Good for routine evaluation of drug efficiency√ Not suitable for studying tumor dissemination
    √ Low cost
    Intraperitoneal model
    √ Easy to perform√ Tumor growth measurements require advanced methods
    √ Good model for studying late stages of EOC√ Not suitable for studying early stages of EOC
    √ Suitable for studying EOC dissemination√ No primary tumor formation
    √ Ascites formation√ Not suitable for studying angiogenesis
    √ Suitable for immunological studies
    √ Low cost
    Orthotopic model
    √ Tumor microenvironment recapitulates physiological conditions√ Difficult to perform
    √ Suitable for studying all stages of disease√ Tumor growth measurement requires advanced methods
    √ Suitable for studying angiogenesis and tumor microenvironment√ High cost
    √ Suitable for immunological studies
    √ Good model to study disease progression
    √ Ascites formation
    下载: 导出CSV

    Table  2.   Classification of EOC mouse models based on source of injected cells

    AdvantagesDisadvantages
    Established human EOC cell lines
    √ Availability of cell lines√ Cell alteration due to high number of passages
    √ Large number of cell lines with various genetic backgrounds√ Not suitable for immunological studies
    √ Easy maintenance
    √ Cells can be genetically manipulated
    √ Low cost
    Established mouse EOC cell lines
    √ Availability of cell lines√ Cell alteration due to high number of passages
    √ Suitable for immunological studies
    √ Easy maintenance
    √ Cells can be genetically manipulated
    √ Low cost
    Patient-derived xenografts
    √ PDX derived from EOC patients, not altered by in vitro culture√ Slow tumor growth
    √ Recapitulates EOC tumor microenvironment√ Difficult maintenance
    √ Specialized training required
    √ Limited access to tumor samples
    √ PDXs cannot be genetically manipulated
    下载: 导出CSV

    Table  3.   List of selected EOC GEMMs

    Gene alteration strategyTarget genesPhenotypeReferences
    AdCre-intrabursal injectionTrp53;Rb1HGSOCFlesken-Nikitin et al., 2003
    AdCre-intrabursal injectionMyc;Trp53;Brca1 HGSOCXing & Orsulic, 2006
    AdCre-intrabursal injectionPten;Pik3ca HGSOCKinross et al., 2012
    AdCre-intrabursal injectionArid1a;Pik3ca OCCCChandler et al., 2015
    AdCre-intrabursal injectionPten;Arid1a OECGuan et al., 2014
    AdCre-intrabursal injectionArid1a;Pten;Apc OECZhai et al., 2016
    Amhr2-mediated Cre expressionDicer1;Pten;Trp53 HGSOCKim et al., 2012
    Pax8-mediated Cre expressionTrp53;Brca1;Brca2 HGSOCPerets et al., 2013
    Ovgp1-mediated Cre expressionApc;Pten OECWu et al., 2016
    Ovgp1-mediated Cre expressionTrp53;Pten;Brca1 HGSOCZhai et al., 2017
    下载: 导出CSV
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出版历程
  • 收稿日期:  2020-12-28
  • 录用日期:  2021-01-26
  • 网络出版日期:  2021-01-28
  • 刊出日期:  2021-03-18

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