卵巢癌是最致命的妇科癌症。化疗作为主要治疗手段，晚期的缓解率仅为60-70%，作为二线治疗则更低。尽管有指南建议，但哪种药物最有效仍不清楚。因此，迫切需要一种优先考虑化疗方案的策略。癌症类器官最近作为体外药物测试的一种方法出现。然而，利用癌症类器官的测试结果评估了有限的临床相关性，特别是在妇科癌症中。因此，我们的目标是生成卵巢癌患者来源的类器官 (PDO)，以评估其药物敏感性以及与患者临床结果的相关性。PDO 是从手术切除过程中获得的新鲜肿瘤中生成的，然后在基质凝胶和适当的生长因子下进行培养。通过相差显微镜和石蜡包埋组织病理学评估 PDO 的形态和分子特征。通过免疫组织化学染色检测PAX8、TP53、WT1、CK7和CK20的表达，并与亲代肿瘤组织和人蛋白图谱数据库进行比较。使用 Titer-Glo® 3D 细胞活力测定对 PDO 进行体外药物测试以确定药物敏感性。测量 PDO 活力，并计算曲线下面积，以比较对各种化合物的反应。计算所选患者的临床结果与体外药物测试结果之间的相关性。我们建立了 31 个 PDO。其中，28个PDO可以扩展，其中分别来自卵巢癌、子宫内膜癌和宫颈癌的15个、11个和2个。 PDO 保留了其起源肿瘤的组织病理学特征。对 10 种卵巢癌 PDO 进行的体外药物测试揭示了个体对推荐药物的不同反应，以及药物敏感性的人际异质性，即使是相同的组织学类型。在四名对铂敏感、耐药或难治的患者中，PDO 药物反应与其临床过程密切相关。使用卵巢癌类器官进行体外药物测试是可行的，并且与患者的临床反应密切相关。这些结果可能有助于精准化疗和个性化筛选新药或新药的开发。© 2024。作者。

Ovarian cancer is the most lethal gynecological cancer. As the primary treatment, chemotherapy has a response rate of only 60-70% in advanced stages, and even lower as a second-line treatment. Despite guideline recommendations, which drugs will be most effective remains unclear. Thus, a strategy to prioritize chemotherapy options is urgently needed. Cancer organoids have recently emerged as a method for in vitro drug testing. However, limited clinical correlations have been assessed with test results from cancer organoids, particularly in gynecological cancers. We therefore aimed to generate patient-derived organoids (PDOs) of ovarian cancer, to assess their drug sensitivities and correlations with patient clinical outcomes.PDOs were generated from fresh tumors obtained during surgical resection, which was then cultured under matrix gel and appropriate growth factors. Morphological and molecular characterization of PDOs were assessed by phase contrast microscopy and paraffin-embedded histopathology. Expressions of PAX8, TP53, WT1, CK7, and CK20 were tested by immunohistochemical staining and compared with parental tumor tissues and the human protein atlas database. PDOs were subjected to in vitro drug testing to determine drug sensitivity using Titer-Glo® 3D Cell Viability Assay. PDO viability was measured, and area under the curve calculated, to compare responses to various compounds. Correlations were calculated between selected patients' clinical outcomes and in vitro drug testing results.We established 31 PDOs. Among them, 28 PDOs can be expanded, including 15, 11, and 2 from ovarian, endometrial, and cervical cancers, respectively. The PDOs preserved the histopathological profiles of their originating tumors. In vitro drug testing of 10 ovarian cancer PDOs revealed individual differential responses to recommended drugs, and interpersonal heterogeneity in drug sensitivity, even with the same histology type. Among four patients who were platinum sensitive, resistant, or refractory, PDO drug responses correlated well with their clinical courses.In vitro drug testing using ovarian cancer organoids is feasible and correlates well with patient clinical responses. These results may facilitate development of precision chemotherapy and personalized screening for repurposed or new drugs.© 2024. The Author(s).