The Use of Endometrial Cancer Patient-Derived Organoid Culture for Drug Sensitivity Testing Is Feasible.
The Use of Endometrial Cancer Patient-Derived Organoid Culture for Drug Sensitivity Testing Is Feasible.
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DOI：
10.1097/igc.0000000000001061
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Smith LH
中科院分区：
文献类型：
--
作者：
Girda E;Huang EC;Leiserowitz GS;Smith LH
补充数字内容可在文本中找到。用于多种肿瘤类型的患者源性类器官（PDO）允许对个体患者的肿瘤特征进行评价。本研究旨在评估PDO体外培养用于子宫内膜癌内分泌和药物敏感试验的可行性。子宫内膜癌细胞从新鲜子宫切除术标本中取出的肿瘤中酶促分离，并在无血清培养基中的基底膜提取物中培养。开发了类器官生长测定以评估包括内分泌治疗在内的多种药物的抑制作用。还制备了类器官培养物，用于与原发肿瘤进行组织学和免疫组织化学比较。15例子宫内膜癌标本成功培养为PDO。小的球形结构在24小时内形成，并且许多继续生长为更大、更致密的类器官，为类器官生长测定提供了基础。STAT 3转录因子抑制剂BBI 608（Napabucasin）强烈抑制几乎所有PDO培养物的生长，表明干细胞编程参与类器官形成和/或生长。在几个PDO标本中观察到不同生长因子受体酪氨酸激酶抑制剂的抑制作用。四种培养物被氟维司群抑制，这意味着雌激素受体信号传导在某些PDO培养物中的重要性。类器官在组织形态学和免疫组化表达方面与其肿瘤来源非常相似。使用子宫内膜癌PDO培养物进行个体患者肿瘤的药物敏感性试验是可行的。PDO模型对临床决策的潜在价值需要临床试验评估。
Supplemental digital content is available in the text. Patient-derived organoids (PDOs), used in multiple tumor types, have allowed evaluation of tumor characteristics from individual patients. This study aimed to assess the feasibility of applying PDO in vitro culture for endocrine-based and drug sensitivity testing in endometrial cancer. Endometrial cancer cells were enzymatically dissociated from tumors retrieved from fresh hysterectomy specimens and cultured within basement membrane extract in serum-free medium. An organoid growth assay was developed to assess the inhibitory effects of a variety of drugs including endocrine treatments. Organoid cultures were also prepared for histological and immunohistochemical comparison to the tumors of origin. Fifteen endometrial cancer specimens were successfully cultured as PDOs. Small spherical structures formed within 24 hours, and many continued to grow to larger, denser organoids, providing the basis for an organoid growth assay. The STAT3 transcription factor inhibitor, BBI608 (Napabucasin), strongly inhibited growth in almost all PDO cultures, suggesting that stemness programing is involved in organoid formation and/or growth. Inhibition by different growth factor receptor tyrosine kinase inhibitors was observed in several PDO specimens. Four cultures were inhibited by fulvestrant, implying the importance of estrogen-receptor signaling in some PDO cultures. Organoids closely resembled their tumors of origin in both histomorphology and immunohistochemical expression. The use of endometrial cancer PDO cultures for development of drug sensitivity testing for individual patient tumors is feasible. The potential value of the PDO model for clinical decision making will require clinical trial evaluation.