Impact of baseline culture conditions of cancer organoids when determining therapeutic response and tumor heterogeneity

Representative models are needed to screen new therapies for patients with cancer. Cancer organoids are a leap forward as a culture model that faithfully represents the disease. Mouse-derived cancer organoids (MDCOs) are becoming increasingly popular, however there has yet to be a standardized metho...

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Bibliographic Details
Published in:Scientific reports 2022-03, Vol.12 (1), p.5205-5205, Article 5205
Main Authors: DeStefanis, Rebecca A., Kratz, Jeremy D., Olson, Autumn M., Sunil, Aishwarya, DeZeeuw, Alyssa K., Gillette, Amani A., Sha, Gioia C., Johnson, Katherine A., Pasch, Cheri A., Clipson, Linda, Skala, Melissa C., Deming, Dustin A.
Format: Article
Language:English
Subjects:
631/1647/1407/652
631/1647/767/2199
631/67
631/67/70
Animals
Cancer
Colon
Genotypes
Heterogeneity
Humanities and Social Sciences
Humans
Mice
multidisciplinary
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - pathology
Organoids
Organoids - pathology
Patients
Science
Science (multidisciplinary)
Tumors
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Summary:Representative models are needed to screen new therapies for patients with cancer. Cancer organoids are a leap forward as a culture model that faithfully represents the disease. Mouse-derived cancer organoids (MDCOs) are becoming increasingly popular, however there has yet to be a standardized method to assess therapeutic response and identify subpopulation heterogeneity. There are multiple factors unique to organoid culture that could affect how therapeutic response and MDCO heterogeneity are assessed. Here we describe an analysis of nearly 3500 individual MDCOs where individual organoid morphologic tracking was performed. Change in MDCO diameter was assessed in the presence of control media or targeted therapies. Individual organoid tracking was identified to be more sensitive to treatment response than well-level assessment. The impact of different generations of mice of the same genotype, different regions of the colon, and organoid specific characteristics including baseline size, passage number, plating density, and location within the matrix were examined. Only the starting size of the MDCO altered the subsequent growth. These results were corroborated using ~ 1700 patient-derived cancer organoids (PDCOs) isolated from 19 patients. Here we establish organoid culture parameters for individual organoid morphologic tracking to determine therapeutic response and growth/response heterogeneity for translational studies.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-08937-z