Polyclonal and clonal organoid models of Barrett oesophagus and oesophageal adenocarcinoma reveal heterogeneity in progression and therapy response

Single-cell–derived clonal organoids from 91 patient- and healthy donor–derived organoids reveal subclonal populations linked to step-wise progression and diverse OAC therapy responses.

• Why it matters: Early heterogeneity in Barrett oesophagus and oesophageal adenocarcinoma limits prevention and treatment, and existing in vitro or animal models do not adequately reproduce this diversity.
• What they did: The study generated 91 PDOs spanning normal oesophagogastric tissue (n=29), Barrett oesophagus (n=13), dysplasia (n=8), and OAC (n=41), then built a single-cell clonal organoid approach to add 28 sc-organoid lines.
• The result: Across the pre-malignant to invasive spectrum, the platform recapitulates step-wise progression, subclonal phylogenetic structure, and diverse responses of OAC to systemic anti-cancer therapies and radiotherapy.

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