Related Experiment Video
Updated: Dec 19, 2025
Multiparametric Tumor Organoid Drug Screening Using Widefield Live-Cell Imaging for Bulk and Single-Organoid Analysis
Published on: December 23, 2022
Metabolic Heterogeneity in Patient Tumor-Derived Organoids by Primary Site and Drug Treatment
Joe T Sharick1,2, Christine M Walsh2, Carley M Sprackling3
1Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States.
Abstract:
New tools are needed to match cancer patients with effective treatments. Patient-derived organoids offer a high-throughput platform to personalize treatments and discover novel therapies. Currently, methods to evaluate drug response in organoids are limited because they overlook cellular heterogeneity. In this study, non-invasive optical metabolic imaging (OMI) of cellular heterogeneity was characterized in breast cancer (BC) and pancreatic cancer (PC) patient-derived organoids. Baseline heterogeneity was analyzed for each patient, demonstrating that single-cell techniques, such as OMI, are required to capture the complete picture of heterogeneity present in a sample. Treatment-induced changes in heterogeneity were also analyzed, further demonstrating that these measurements greatly complement current techniques that only gauge average cellular response. Finally, OMI of cellular heterogeneity in organoids was evaluated as a predictor of clinical treatment response for the first time. Organoids were treated with the same drugs as the patient's prescribed regimen, and OMI measurements of heterogeneity were compared to patient outcome. OMI distinguished subpopulations of cells with divergent and dynamic responses to treatment in living organoids without the use of labels or dyes. OMI of organoids agreed with long-term therapeutic response in patients. With these capabilities, OMI could serve as a sensitive high-throughput tool to identify optimal therapies for individual patients, and to develop new effective therapies that address cellular heterogeneity in cancer.
Insights
Optical metabolic imaging (OMI) can now assess cellular heterogeneity in patient-derived organoids. This novel approach predicts patient treatment response, aiding personalized cancer therapy development.
Area of Science:
- Oncology
- Biotechnology
- Medical Imaging
Background:
- Personalized cancer treatment requires matching patients with effective therapies.
- Patient-derived organoids are a promising platform for drug screening and therapy discovery.
- Current methods for evaluating drug response in organoids fail to capture cellular heterogeneity.
Purpose of the Study:
- To characterize optical metabolic imaging (OMI) of cellular heterogeneity in breast and pancreatic cancer patient-derived organoids.
- To assess OMI's ability to predict clinical treatment response based on organoid drug sensitivity.
Main Methods:
- Non-invasive optical metabolic imaging (OMI) was used to analyze cellular heterogeneity in patient-derived organoids.
- Baseline and treatment-induced heterogeneity were measured in breast and pancreatic cancer organoids.
- OMI measurements of organoid drug response were compared to patient clinical outcomes.
Main Results:
- Single-cell OMI revealed significant baseline cellular heterogeneity in patient-derived organoids.
- OMI effectively captured treatment-induced changes in cellular heterogeneity, complementing average response metrics.
- OMI measurements of organoid drug response accurately predicted long-term patient therapeutic outcomes.
Conclusions:
- Optical metabolic imaging (OMI) is a sensitive, high-throughput tool for analyzing cellular heterogeneity in cancer organoids.
- OMI can identify optimal therapies for individual cancer patients by predicting clinical treatment response.
- This technology holds potential for developing novel cancer therapies that target cellular heterogeneity.
