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Updated: Oct 1, 2025
Multiparametric Tumor Organoid Drug Screening Using Widefield Live-Cell Imaging for Bulk and Single-Organoid Analysis
Published on: December 23, 2022
Technologies to Assess Drug Response and Heterogeneity in Patient-Derived Cancer Organoids
Melissa C Skala1,2,3, Dustin A Deming3,4,5, Jeremy D Kratz3,4,6
1Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA;
Abstract:
Patient-derived cancer organoids (PDCOs) are organotypic 3D cultures grown from patient tumor samples. PDCOs provide an exciting opportunity to study drug response and heterogeneity within and between patients. This research can guide new drug development and inform clinical treatment planning. We review technologies to assess PDCO drug response and heterogeneity, discuss best practices for clinically relevant drug screens, and assert the importance of quantifying single-cell and organoid heterogeneity to characterize response. Autofluorescence imaging of PDCO growth and metabolic activity is highlighted as a compelling method to monitor single-cell and single-organoid response robustly and reproducibly. We also speculate on the future of PDCOs in clinical practice and drug discovery.Future development will require standardization of assessment methods for both morphology and function in PDCOs, increased throughput for new drug development, prospective validation with patient outcomes, and robust classification algorithms.
Insights
Patient-derived cancer organoids (PDCOs) offer a powerful model for studying drug response and tumor heterogeneity. Standardized methods and advanced imaging are key to advancing PDCOs for drug discovery and clinical applications.
Area of Science:
- Oncology
- Biotechnology
- Drug Discovery
Background:
- Patient-derived cancer organoids (PDCOs) are 3D cultures from patient tumors, valuable for studying drug response and heterogeneity.
- PDCOs hold promise for guiding new drug development and personalizing clinical treatment strategies.
Purpose of the Study:
- To review technologies for assessing PDCO drug response and heterogeneity.
- To discuss best practices for clinically relevant drug screening using PDCOs.
- To emphasize quantifying single-cell and organoid heterogeneity for response characterization.
Main Methods:
- Review of existing technologies for PDCO drug response and heterogeneity assessment.
- Discussion of best practices for drug screening.
- Highlighting autofluorescence imaging for monitoring PDCO growth and metabolic activity.
Main Results:
- Autofluorescence imaging is presented as a robust method for monitoring single-cell and single-organoid response.
- The importance of quantifying heterogeneity for characterizing drug response is asserted.
Conclusions:
- Standardization of assessment methods, increased throughput, and prospective validation are crucial for future PDCO development.
- PDCOs are poised for significant roles in clinical practice and drug discovery, requiring further technological and methodological advancements.
