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Updated: Dec 21, 2025
Measuring Real-time Drug Response in Organotypic Tumor Tissue Slices
Published on: May 2, 2020
Measuring Real-time Drug Response in Organotypic Tumor Tissue Slices
Nao Nishida-Aoki1, Andrew J Bondesson2, Taranjit S Gujral3
1Division of Human Biology, Fred Hutchinson Cancer Research Center.
Abstract:
Tumor tissues are composed of cancerous cells, infiltrated immune cells, endothelial cells, fibroblasts, and extracellular matrix. This complex milieu constitutes the tumor microenvironment (TME) and can modulate response to therapy in vivo or drug response ex vivo. Conventional cancer drug discovery screens are carried out on cells cultured in a monolayer, a system critically lacking the influence of TME. Thus, experimental systems that integrate sensitive and high-throughput assays with physiological TME will strengthen the preclinical drug discovery process. Here, we introduce ex vivo tumor tissue slice culture as a platform for medium-high-throughput drug screening. Organotypic tissue slice culture constitutes precisely-cut, thin tumor sections that are maintained with the support of a porous membrane in a liquid-air interface. In this protocol, we describe the preparation and maintenance of tissue slices prepared from mouse tumors and tumors from patient-derived xenograft (PDX) models. To assess changes in tissue viability in response to drug treatment, we leveraged a biocompatible luminescence-based viability assay that enables real-time, rapid, and sensitive measurement of viable cells in the tissue. Using this platform, we evaluated dose-dependent responses of tissue slices to the multi-kinase inhibitor, staurosporine, and cytotoxic agent, doxorubicin. Further, we demonstrate the application of tissue slices for ex vivo pharmacology by screening 17 clinical and preclinical drugs on tissue slices prepared from a single PDX tumor. Our physiologically-relevant, highly-sensitive, and robust ex vivo screening platform will greatly strengthen preclinical oncology drug discovery and treatment decision making.
Insights
This study introduces ex vivo tumor tissue slice culture for preclinical cancer drug discovery. This method better mimics the tumor microenvironment (TME), improving drug screening accuracy and aiding treatment decisions.
Area of Science:
- Oncology
- Cancer Biology
- Drug Discovery
Background:
- The tumor microenvironment (TME) significantly influences cancer progression and therapeutic response.
- Conventional monolayer cell cultures lack the TME's complexity, limiting their predictive power in drug discovery.
- There is a need for experimental systems that integrate high-throughput screening with physiological TME.
Purpose of the Study:
- To develop and validate an ex vivo tumor tissue slice culture platform for medium-to-high-throughput drug screening.
- To assess the utility of this platform for evaluating drug responses in a physiologically relevant context.
- To enhance preclinical oncology drug discovery and inform treatment strategies.
Main Methods:
- Organotypic tumor tissue slices were prepared from mouse and patient-derived xenograft (PDX) tumors.
- Tissue slices were maintained at a liquid-air interface on a porous membrane.
- A luminescence-based viability assay was used to measure drug-induced changes in cell viability in real-time.
- Dose-dependent responses to staurosporine and doxorubicin were evaluated.
- 17 clinical and preclinical drugs were screened using PDX tumor slices.
Main Results:
- The ex vivo tissue slice culture platform demonstrated sensitivity and robustness in assessing drug responses.
- Dose-dependent effects of staurosporine and doxorubicin on tissue viability were successfully measured.
- The platform enabled the screening of multiple drugs on tissue slices from a single PDX tumor, showcasing its applicability for ex vivo pharmacology.
- The system provides a physiologically relevant model for evaluating drug efficacy.
Conclusions:
- Ex vivo tumor tissue slice culture is a powerful and sensitive platform for medium-to-high-throughput drug screening.
- This approach better recapitulates the tumor microenvironment compared to traditional methods.
- The developed platform can significantly advance preclinical oncology drug discovery and aid in personalized treatment decision-making.
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