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. 2025 Mar 19;38(3):72.
doi: 10.1007/s13577-025-01206-x.

Establishment and characterization of novel patient-derived esophageal tumoroids with long-term cultivability

Takashi Urano  1 , Etsuko Yokota  1 , Miki Iwai  2 , Takuro Yukawa  1 , Yoshio Naomoto  1 , Nagio Takigawa  2   3 , Hideyo Fujiwara  4 , Takashi Akiyama  4 , Minoru Haisa  5 , Takuya Fukazawa  6   7 , Tomoki Yamatsuji  1
Affiliations

Establishment and characterization of novel patient-derived esophageal tumoroids with long-term cultivability

Takashi Urano et al. Hum Cell. .

Abstract

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.

Keywords: ERBB2; ERBB3; Antibody drugs; Esophageal cancer; Molecular targeted therapy; Organoid.

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Conflict of interest statement

Declarations. Conflict of interest: Nagio Takigawa discloses grants and personal fees from Eli Lilly Japan, Japan. Ethical approval: Approval of the research protocol by an Institutional Reviewer Board: The research protocol was approved by the Ethics Committee of Kawasaki Medical School (Reference Number: 3171–7). Animal studies: All animal studies were approved by the Animal Research Committee of Kawasaki Medical School (Reference Number: 23–047). The care and use of animals were conducted in in accordance with the committee regulations. Informed consent: Informed consent was obtained from all the patients as per the study protocol. Written informed consent was obtained from all the participants. The patient who participated in the present study signed an informed consent form approved by the responsible authority.

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