Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers
Tara L. Hogenson, … , Wen Wee Ma, Martin E. Fernandez-Zapico
Tara L. Hogenson, … , Wen Wee Ma, Martin E. Fernandez-Zapico
Published October 18, 2022
Citation Information: JCI Insight. 2022;7(22):e158060. https://doi.org/10.1172/jci.insight.158060.
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Clinical Medicine Oncology Therapeutics

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

Abstract

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).

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-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

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Figure 5

The effect of PDO culture media on clinical correlation: a case study.

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The effect of PDO culture media on clinical correlation: a case study. (...
(A) Donor patient treatment history for PDO HO107. After surgery, this patient received a single dose of FOLFIRINOX (folinic acid + 5-FU + irinotecan + oxaliplatin) followed by 5-FU and liposomal irinotecan. (B) CT scans of donor patient for PDO HO107 before and after treatment with progressive disease (PD), where a metastatic liver lesion of 24.2 mm developed following treatment with FOLFOX. (C) Relative AUC values for PDO HO107 in response to 5-FU and oxaliplatin in WNT media. Each dot represents the relative AUC for 1 replicate derived from the line graphs in Supplemental Figure 14A; n = 12. (D) Relative AUC values for PDO HO107 in response to 5-FU and oxaliplatin in PaTOM media. Each dot represents the relative AUC for 1 replicate derived from the line graphs in Supplemental Figure 14B; n = 6. The data in this figure for HO17, HO44, HO163, HO219, and HO228 were derived from Supplemental Figure 8. PDO response was determined as intermediate, sensitive, or resistant using Jenks Natural Breaks. The arrow next to the PDO number indicates the PDO response corresponding to the patient tumor response in the CT scan. (E) GSEA using Hallmark gene sets showing enriched gene sets in PDAC PDO HO107 in WNT media. NES, normalized enrichment score.