An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity
An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity
复制标题
DOI：
10.1038/s41591-019-0422-6
复制
发表时间：
2019-05-01
期刊：
影响因子：
82.9
通讯作者：
Clevers, Hans
中科院分区：
文献类型：
--
作者：
Kopper, Oded;de Witte, Chris J.;Clevers, Hans
卵巢癌(OC)是一种异质性疾病，通常在晚期诊断。忠实地捕捉OC的特征和肿瘤异质性的体外实验模型是有限的，很难建立。我们提出了一种方案，使有机化合物的有效衍生和长期扩展成为可能。利用这个方案，我们已经建立了来自32名患者的56个器官系，代表了OC的所有主要亚型。OC类有机物概括了其来源的相关病变的组织学和基因组特征，说明了患者内部和患者之间的异质性，并且可以进行基因改造。我们发现OC有机化合物可用于药物筛选试验，捕捉不同肿瘤亚型对金标准铂类化疗的反应，包括在复发疾病中获得化疗耐药性。最后，OC有机化合物可以被异种移植，从而能够进行体内药物敏感性分析。综上所述，这表明了它们在研究和个性化医学方面的潜在应用。
Ovarian cancer (OC) is a heterogeneous disease usually diagnosed at a late stage. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of OC are limited and hard to establish. We present a protocol that enables efficient derivation and long-term expansion of OC organoids. Utilizing this protocol, we have established 56 organoid lines from 32 patients, representing all main subtypes of OC. OC organoids recapitulate histological and genomic features of the pertinent lesion from which they were derived, illustrating intra-and interpatient heterogeneity, and can be genetically modified. We show that OC organoids can be used for drug-screening assays and capture different tumor subtype responses to the gold standard platinum-based chemotherapy, including acquisition of chemoresistance in recurrent disease. Finally, OC organoids can be xenografted, enabling in vivo drug-sensitivity assays. Taken together, this demonstrates their potential application for research and personalized medicine.