Urano Takashi, Yokota Etsuko, Iwai Miki, Yukawa Takuro, Naomoto Yoshio, Takigawa Nagio, Fujiwara Hideyo, Akiyama Takashi, Haisa Minoru, Fukazawa Takuya, Yamatsuji Tomoki
Department of General Surgery, Kawasaki Medical School, Okayama, 700-8505, Japan.
General Medical Center Research Unit, Kawasaki Medical School, Okayama, 700-8505, Japan.
Hum Cell. 2025 Mar 19;38(3):72. doi: 10.1007/s13577-025-01206-x.
Esophageal cancer is an aggressive and fatal disease classified into two distinct histologic types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). To develop novel therapeutic strategies, it is important to establish preclinical models of esophageal carcinoma. In this study, we successfully established three types of human esophageal cancer organoids (tumoroids) from surgical specimens for long-term culture. Two of the tumoroids were derived from ESCC and one from EAC, which arose from Barrett's esophagus. Whole-exome sequencing revealed that the tumoroids inherited genetic mutations from the parental tumors and patient-derived tumor xenografts closely mimicked the pathology of the original esophageal cancers. In addition to whole-exome analysis, copy number and immunohistochemical analyses demonstrated HER2 expression and amplification as well as HER3 expression and mutation in esophageal tumoroids derived from adenocarcinoma in Barrett's esophagus. HER2-targeting antibody-drug conjugates (ADCs), trastuzumab deruxtecan (T-DXd), and patritumab deruxtecan (P-DXd) effectively suppressed the viability of the tumoroids. Therefore, the establishment of esophageal tumoroids with long-term cultivability makes it possible to obtain reproducible basic data, including drug sensitivity studies, which are important for the development of personalized therapies and treatment strategies.
食管癌是一种侵袭性致命疾病，分为两种不同的组织学类型：食管鳞状细胞癌（ESCC）和食管腺癌（EAC）。为了开发新的治疗策略，建立食管癌的临床前模型很重要。在本研究中，我们成功地从手术标本中建立了三种类型的人食管癌类器官（肿瘤类器官）用于长期培养。其中两种肿瘤类器官来源于ESCC，一种来源于巴雷特食管引起的EAC。全外显子测序显示，肿瘤类器官继承了亲代肿瘤的基因突变，患者来源的肿瘤异种移植密切模拟了原始食管癌的病理特征。除了全外显子分析，拷贝数和免疫组化分析还显示，来源于巴雷特食管腺癌的食管肿瘤类器官中存在HER2表达和扩增以及HER3表达和突变。靶向HER2的抗体药物偶联物（ADCs）、曲妥珠单抗德鲁昔单抗（T-DXd）和帕妥珠单抗德鲁昔单抗（P-DXd）有效抑制了肿瘤类器官的活力。因此，建立具有长期可培养性的食管肿瘤类器官使得获得可重复的基础数据成为可能，包括药物敏感性研究，这对个性化治疗和治疗策略的发展很重要。
