Towards personalized induction therapy for esophageal adenocarcinoma: organoids derived from endoscopic biopsy recapitulate the pre-treatment tumor

• Published in: Scientific reports Vol. 10; no. 1; p. 14514
• Main Authors: Derouet, Mathieu F., Allen, Jonathan, Wilson, Gavin W., Ng, Christine, Radulovich, Nikolina, Kalimuthu, Sangeetha, Tsao, Ming-Sound, Darling, Gail E., Yeung, Jonathan C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.09.2020; Nature Publishing Group
• Subjects: 631/67/1504/1477; 631/67/70; Adenocarcinoma - drug therapy; Adult; Aged; Aged, 80 and over; Barrett Esophagus - drug therapy; Chemotherapy; Esophageal cancer; Esophageal Neoplasms - drug therapy; Female; Filamentation; Histology; Humanities and Social Sciences; Humans; Induction Chemotherapy - methods; Induction therapy; Lasers; Male; Middle Aged; multidisciplinary; Organoids - cytology; Precision Medicine - methods; Science; Science (multidisciplinary); Surgery; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-71589-4

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 naïve esophageal adenocarcinomas. Histologic characterization and molecular characterization of organoids by whole exome sequencing demonstrated recapitulation of the tumors’ histology and genomic (~ 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.