Abstract
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 3,500 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. Here we establish organoid culture parameters for individual organoid morphologic tracking to determine therapeutic response and growth/response heterogeneity for translational studies using murine colorectal cancer organoids.
Competing Interest Statement
Dr. Deming has received research support from Bayer and Takeda. He has also been compensated for serving on a scientific advisory board for Bayer. The other authors declare no potential conflict of interest.
Footnotes
Funding/Acknowledgements This project was supported by NIH grants R37 CA226526 (DAD), T32 AG000213 (JDK), T32 CA009135 (KAJ), and P30 CA014520 (Core Grant, University of Wisconsin Carbone Cancer Center). The Skala laboratory is supported by NIH grants R01 CA185747 (MCS), R01 CA205101 (MCS), R01 CA211082 (MCS), U01 HL145792 (MCS). Additional support was provided from Funk Out Cancer (DAD), the Cathy Wingert Colorectal Cancer Research Fund (DAD), and the ACI/Schwenn Family Professorship (DAD).