Towards personalized induction therapy for esophageal adenocarcinoma: organoids derived from endoscopic biopsy recapitulate the pre-treatment tumor
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 dev...
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| Published in | Scientific reports Vol. 10; no. 1; p. 14514 |
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| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
03.09.2020
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2045-2322 2045-2322 |
| DOI | 10.1038/s41598-020-71589-4 |
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| Abstract | 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. |
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| AbstractList | 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.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. 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. |
| ArticleNumber | 14514 |
| Author | Derouet, Mathieu F. Kalimuthu, Sangeetha Darling, Gail E. Allen, Jonathan Ng, Christine Tsao, Ming-Sound Yeung, Jonathan C. Radulovich, Nikolina Wilson, Gavin W. |
| Author_xml | – sequence: 1 givenname: Mathieu F. surname: Derouet fullname: Derouet, Mathieu F. organization: Latner Thoracic Surgery Research Laboratories, Princess Margaret Cancer Research Tower, University Health Network – sequence: 2 givenname: Jonathan surname: Allen fullname: Allen, Jonathan organization: Latner Thoracic Surgery Research Laboratories, Princess Margaret Cancer Research Tower, University Health Network – sequence: 3 givenname: Gavin W. surname: Wilson fullname: Wilson, Gavin W. organization: Latner Thoracic Surgery Research Laboratories, Princess Margaret Cancer Research Tower, University Health Network – sequence: 4 givenname: Christine surname: Ng fullname: Ng, Christine organization: Princess Margaret Cancer Centre, University Health Network – sequence: 5 givenname: Nikolina surname: Radulovich fullname: Radulovich, Nikolina organization: Princess Margaret Cancer Centre, University Health Network – sequence: 6 givenname: Sangeetha surname: Kalimuthu fullname: Kalimuthu, Sangeetha organization: Department of Pathology, University Health Network – sequence: 7 givenname: Ming-Sound surname: Tsao fullname: Tsao, Ming-Sound organization: Princess Margaret Cancer Centre, University Health Network, Department of Pathology, University Health Network – sequence: 8 givenname: Gail E. surname: Darling fullname: Darling, Gail E. organization: Latner Thoracic Surgery Research Laboratories, Princess Margaret Cancer Research Tower, University Health Network, Division of Thoracic Surgery, Toronto General Hospital, University Health Network – sequence: 9 givenname: Jonathan C. surname: Yeung fullname: Yeung, Jonathan C. email: jonathan.yeung@uhn.ca organization: Latner Thoracic Surgery Research Laboratories, Princess Margaret Cancer Research Tower, University Health Network, Division of Thoracic Surgery, Toronto General Hospital, University Health Network |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32884042$$D View this record in MEDLINE/PubMed |
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| Snippet | Esophageal adenocarcinoma has few known recurrent mutations and therefore robust, reliable and reproducible patient-specific models are needed for personalized... |
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| SubjectTerms | 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 |
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| Title | Towards personalized induction therapy for esophageal adenocarcinoma: organoids derived from endoscopic biopsy recapitulate the pre-treatment tumor |
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