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 6

PDO therapeutic agent sensitivity correlates with patient tumor response.

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PDO therapeutic agent sensitivity correlates with patient tumor response...
(A) CT scans of donor patient for PDO HO20 before and after treatment with partial response (PR), where the lesion decreased from 61.6 mm to 50.8 mm after 2 cycles of treatment with vemurafenib. (B) Percentage cell viability and relative AUC values in response to vemurafenib for 7 CRC PDOs, showing that PDO HO20 is sensitive to vemurafenib; n = 7. (C) CT scans of donor patients before and after treatment showing stable disease (SD) in 1 lesion (HO90) and progressive disease (PD) in 1 lesion (HO123) following treatment with regorafenib. (D) Percentage cell viability and relative AUC values in response to regorafenib for 7 CRC PDOs, showing that PDO HO90 is intermediate and HO123 is resistant to regorafenib; n = 7. For line graphs, dashed lines indicate sensitive, solid lines indicate intermediate, dotted lines indicate resistant, categorized using the Jenks Natural Breaks algorithm. The HO number with an asterisk and the thickest line in the line graphs indicate PDO response corresponding to the patient tumor response shown in the CT scan. The arrow next to the HO number in the relative AUC graph indicates the PDO corresponding to the donor tumor.