Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers

• DOI: 10.1172/jci.insight.158060
• Publication Date: 2022-10-18T16:00:24Z
• Authors: 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-...; 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. Sch...; 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-...; Wen Wee Ma; Martin E. Fernand...
• Keywords: 0301 basic medicine; R; 610; Therapeutics; Colorectal cancer; Culture Media; 3. Good health; [SDV] Life Sciences [q-bio]; Organoids; Pancreatic Neoplasms; 03 medical and health sciences; Oncology; 617; Medicine; Humans; Drug therapy; Clinical Medicine; Liver cancer; Gastrointestinal Neoplasms

BACKGROUNDA 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.METHODSWe 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.RESULTSWe 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.CONCLUSIONWhile 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 REGISTRATIONNot applicable.FUNDINGThe 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).