Towards personalized induction therapy for esophageal adenocarcinoma: organoids derived from endoscopic biopsy recapitulate the pre-treatment tumor
Towards personalized induction therapy for esophageal adenocarcinoma: organoids derived from endoscopic biopsy recapitulate the pre-treatment tumor
复制标题
DOI：
10.1038/s41598-020-71589-4
复制
发表时间：
2020-09-03
影响因子：
4.6
通讯作者：
Yeung, Jonathan C.
中科院分区：
文献类型：
--
作者：
Derouet, Mathieu F.;Allen, Jonathan;Yeung, Jonathan C.
食管癌很少有已知的复发性突变，因此个性化治疗需要稳健、可靠和可重复的患者特异性模型。患者源性类器官培养是一种可能允许食管癌个性化研究和个性化诱导治疗发展的策略。因此，我们制定了一项方案，通过内镜下食管腺癌活检建立EAC类器官。通过全外显子组测序对类器官的组织学特征和分子特征进行表征，证实了肿瘤的组织学和基因组特征（类似于60% SNV重叠）。使用临床合适的化疗药物和靶向治疗的药物测试显示，患者的肿瘤反应和相应的类器官反应之间存在重叠。此外，我们确定Barrett食管上皮是类器官培养污染的潜在来源。总之，类器官可以从食管腺癌的内镜活检中培养出来，并能概括原发肿瘤。该模型有望为食管癌患者提供更好的个性化治疗。
Esophageal adenocarcinoma has few known recurrent mutations and therefore robust, reliable and reproducible patient-specific models are needed for personalized treatment. Patient-derived organoid culture is a strategy that may allow for the personalized study of esophageal adenocarcinoma and the development of personalized induction therapy. We therefore developed a protocol to establish EAC organoids from endoscopic biopsies of naive esophageal adenocarcinomas. Histologic characterization and molecular characterization of organoids by whole exome sequencing demonstrated recapitulation of the tumors' histology and genomic (similar to 60% SNV overlap) characteristics. Drug testing using clinically appropriate chemotherapeutics and targeted therapeutics showed an overlap between the patient's tumor response and the corresponding organoids' response. Furthermore, we identified Barrett's esophagus epithelium as a potential source of organoid culture contamination. In conclusion, organoids can be robustly cultured from endoscopic biopsies of esophageal adenocarcinoma and recapitulate the originating tumor. This model demonstrates promise as a tool to better personalize therapy for esophageal adenocarcinoma patients.