Modelling esophageal adenocarcinoma and Barrett's esophagus with patient-derived organoids

Julia V Milne; Ebtihal H Mustafa; Nicholas J Clemons

doi:10.3389/fmolb.2024.1382070

Modelling esophageal adenocarcinoma and Barrett's esophagus with patient-derived organoids

Front Mol Biosci. 2024 Apr 24:11:1382070. doi: 10.3389/fmolb.2024.1382070. eCollection 2024.

Authors

Julia V Milne^{1

2}, Ebtihal H Mustafa^{1

2}, Nicholas J Clemons^{1

2}

Affiliations

¹ Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
² Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.

Abstract

Currently, esophageal adenocarcinoma (EAC) research is hindered by a dearth of adequate models to study this disease. Traditional cell line and genetically engineered mouse models are lacking in biological and physiological significance, whilst the inefficiency of patient-derived xenografts limit their potential applications. This review describes the landscape of EAC research using patient-derived organoids (PDOs). Here, we detail the methods of establishment and optimization of EAC PDO cultures, as well as current and prospective applications of these models. We further highlight a crucial knowledge gap in the mechanisms of EAC transformation from its precursor lesion, Barrett's esophagus (BE). As such, we also describe the culture requirements of BE PDOs and attempts to model tumorigenesis using PDO models.

Keywords: Barrett’s esophagus; esophageal adenocarcinoma (EAC); esophageal cancer (EC); models of cancer; organoids; patient-derived organoid (PDO); tumorigenesis.

Publication types

Review

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work is supported by funding from the National Health and Medical Research Council, Peter MacCallum Foundation. The authors declare that this review received funding from Astex Pharmaceuticals (UK). The funder was not involved in the design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.