Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers
BACKGROUND A patient-derived organoid (PDO) platform may serve as a promising tool for translational cancer research. In this study, we evaluated PDO’s ability to predict clinical response to gastrointestinal (GI) cancers.METHODS We generated PDOs from primary and metastatic lesions of patients with...
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| Format: | Article |
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American Society for Clinical investigation
2022-11-01
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| Series: | JCI Insight |
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| Online Access: | https://doi.org/10.1172/jci.insight.158060 |
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| author | Tara L. Hogenson Hao Xie William J. Phillips Merih D. Toruner Jenny J. Li Isaac P. Horn Devin J. Kennedy Luciana L. Almada David L. Marks Ryan M. Carr Murat Toruner Ashley N. Sigafoos Amanda N. Koenig-Kappes Rachel L.O. Olson Ezequiel J. Tolosa Cheng Zhang Hu Li Jason D. Doles Jonathan Bleeker Michael T. Barrett James H. Boyum Benjamin R. Kipp Amit Mahipal Joleen M. Hubbard Temperance J. Scheffler Hanson Gloria M. Petersen Surendra Dasari Ann L. Oberg Mark J. Truty Rondell P. Graham Michael J. Levy Mojun Zhu Daniel D. Billadeau Alex A. Adjei Nelson Dusetti Juan L. Iovanna Tanios S. Bekaii-Saab Wen Wee Ma Martin E. Fernandez-Zapico |
| author_facet | Tara L. Hogenson Hao Xie William J. Phillips Merih D. Toruner Jenny J. Li Isaac P. Horn Devin J. Kennedy Luciana L. Almada David L. Marks Ryan M. Carr Murat Toruner Ashley N. Sigafoos Amanda N. Koenig-Kappes Rachel L.O. Olson Ezequiel J. Tolosa Cheng Zhang Hu Li Jason D. Doles Jonathan Bleeker Michael T. Barrett James H. Boyum Benjamin R. Kipp Amit Mahipal Joleen M. Hubbard Temperance J. Scheffler Hanson Gloria M. Petersen Surendra Dasari Ann L. Oberg Mark J. Truty Rondell P. Graham Michael J. Levy Mojun Zhu Daniel D. Billadeau Alex A. Adjei Nelson Dusetti Juan L. Iovanna Tanios S. Bekaii-Saab Wen Wee Ma Martin E. Fernandez-Zapico |
| author_sort | Tara L. Hogenson |
| collection | DOAJ |
| description | BACKGROUND A patient-derived organoid (PDO) platform may serve as a promising tool for translational cancer research. In this study, we evaluated PDO’s ability to predict clinical response to gastrointestinal (GI) cancers.METHODS We generated PDOs from primary and metastatic lesions of patients with GI cancers, including pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, and cholangiocarcinoma. We compared PDO response with the observed clinical response for donor patients to the same treatments.RESULTS We report an approximately 80% concordance rate between PDO and donor tumor response. Importantly, we found a profound influence of culture media on PDO phenotype, where we showed a significant difference in response to standard-of-care chemotherapies, distinct morphologies, and transcriptomes between media within the same PDO cultures.CONCLUSION While we demonstrate a high concordance rate between donor tumor and PDO, these studies also showed the important role of culture media when using PDOs to inform treatment selection and predict response across a spectrum of GI cancers.TRIAL REGISTRATION Not applicable.FUNDING The Joan F. & Richard A. Abdoo Family Fund in Colorectal Cancer Research, GI Cancer program of the Mayo Clinic Cancer Center, Mayo Clinic SPORE in Pancreatic Cancer, Center of Individualized Medicine (Mayo Clinic), Department of Laboratory Medicine and Pathology (Mayo Clinic), Incyte Pharmaceuticals and Mayo Clinic Hepatobiliary SPORE, University of Minnesota-Mayo Clinic Partnership, and the Early Therapeutic program (Department of Oncology, Mayo Clinic). |
| first_indexed | 2024-03-11T12:07:13Z |
| format | Article |
| id | doaj.art-f973dfbdbe53458f81a1c8da0742e768 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:07:13Z |
| publishDate | 2022-11-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-f973dfbdbe53458f81a1c8da0742e7682023-11-07T16:24:51ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-11-01722Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancersTara L. HogensonHao XieWilliam J. PhillipsMerih D. TorunerJenny J. LiIsaac P. HornDevin J. KennedyLuciana L. AlmadaDavid L. MarksRyan M. CarrMurat TorunerAshley N. SigafoosAmanda N. Koenig-KappesRachel L.O. OlsonEzequiel J. TolosaCheng ZhangHu LiJason D. DolesJonathan BleekerMichael T. BarrettJames H. BoyumBenjamin R. KippAmit MahipalJoleen M. HubbardTemperance J. Scheffler HansonGloria M. PetersenSurendra DasariAnn L. ObergMark J. TrutyRondell P. GrahamMichael J. LevyMojun ZhuDaniel D. BilladeauAlex A. AdjeiNelson DusettiJuan L. IovannaTanios S. Bekaii-SaabWen Wee MaMartin E. Fernandez-ZapicoBACKGROUND A patient-derived organoid (PDO) platform may serve as a promising tool for translational cancer research. In this study, we evaluated PDO’s ability to predict clinical response to gastrointestinal (GI) cancers.METHODS We generated PDOs from primary and metastatic lesions of patients with GI cancers, including pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, and cholangiocarcinoma. We compared PDO response with the observed clinical response for donor patients to the same treatments.RESULTS We report an approximately 80% concordance rate between PDO and donor tumor response. Importantly, we found a profound influence of culture media on PDO phenotype, where we showed a significant difference in response to standard-of-care chemotherapies, distinct morphologies, and transcriptomes between media within the same PDO cultures.CONCLUSION While we demonstrate a high concordance rate between donor tumor and PDO, these studies also showed the important role of culture media when using PDOs to inform treatment selection and predict response across a spectrum of GI cancers.TRIAL REGISTRATION Not applicable.FUNDING The Joan F. & Richard A. Abdoo Family Fund in Colorectal Cancer Research, GI Cancer program of the Mayo Clinic Cancer Center, Mayo Clinic SPORE in Pancreatic Cancer, Center of Individualized Medicine (Mayo Clinic), Department of Laboratory Medicine and Pathology (Mayo Clinic), Incyte Pharmaceuticals and Mayo Clinic Hepatobiliary SPORE, University of Minnesota-Mayo Clinic Partnership, and the Early Therapeutic program (Department of Oncology, Mayo Clinic).https://doi.org/10.1172/jci.insight.158060OncologyTherapeutics |
| spellingShingle | Tara L. Hogenson Hao Xie William J. Phillips Merih D. Toruner Jenny J. Li Isaac P. Horn Devin J. Kennedy Luciana L. Almada David L. Marks Ryan M. Carr Murat Toruner Ashley N. Sigafoos Amanda N. Koenig-Kappes Rachel L.O. Olson Ezequiel J. Tolosa Cheng Zhang Hu Li Jason D. Doles Jonathan Bleeker Michael T. Barrett James H. Boyum Benjamin R. Kipp Amit Mahipal Joleen M. Hubbard Temperance J. Scheffler Hanson Gloria M. Petersen Surendra Dasari Ann L. Oberg Mark J. Truty Rondell P. Graham Michael J. Levy Mojun Zhu Daniel D. Billadeau Alex A. Adjei Nelson Dusetti Juan L. Iovanna Tanios S. Bekaii-Saab Wen Wee Ma Martin E. Fernandez-Zapico Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers JCI Insight Oncology Therapeutics |
| title | Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers |
| title_full | Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers |
| title_fullStr | Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers |
| title_full_unstemmed | Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers |
| title_short | Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers |
| title_sort | culture media composition influences patient derived organoid ability to predict therapeutic responses in gastrointestinal cancers |
| topic | Oncology Therapeutics |
| url | https://doi.org/10.1172/jci.insight.158060 |
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