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Measuring Real-time Drug Response in Organotypic Tumor Tissue Slices
Published on: May 2, 2020
Evaluation of drug-induced injury and human response in precision-cut tissue slices
Alison E M Vickers1, Robyn L Fisher
1Drug Safety Evaluation, Allergan Inc., Irvine, CA 92623, USA. vickers_alison@allergan.com
Abstract:
1.Drug induced organ injury is multifaceted, encompassing a spectrum of cell types and numerous networks reflecting cell-cell and cell-matrix interactions. Characterization of drug induced side effects and human response can be addressed in organ slice models. 2.The application of human tissue to various organ slice models including liver, intestine, kidney, liver-blood co-cultures and thyroid enhances our ability to focus on the clinical relevance of side effects identified in animal studies for human, and to evaluate potential biomarkers of the side effects. Dose-response relationships can help discern drug concentrations which alter organ function or affect morphology, to identify drug concentrationswhich could pose a risk for humans. 3.Insight into pathways of organ injury, by incorporating gene and protein expression profiling, with functional measurements and morphology, aid to define species differences and sensitivity. 4.Human organ slice studies are valuable for bridging the extrapolation of animal derived data and for identifying mechanisms relevant for humans, thereby expanding the scope of translational research for drug safety assessment.
Insights
Human organ slice models offer a powerful tool to study drug-induced organ injury and side effects. These models enhance the clinical relevance of findings and improve drug safety assessment for humans.
Area of Science:
- Toxicology
- Pharmacology
- Translational Research
Background:
- Drug-induced organ injury involves complex cell and matrix interactions.
- Understanding human responses to drug side effects is crucial for safety assessment.
Purpose of the Study:
- To characterize drug-induced side effects and human response using organ slice models.
- To evaluate the clinical relevance of animal study findings in humans.
- To identify potential biomarkers for drug-induced side effects.
Main Methods:
- Utilizing human tissue in various organ slice models (liver, intestine, kidney, co-cultures, thyroid).
- Establishing dose-response relationships to determine critical drug concentrations.
- Integrating gene/protein expression profiling with functional and morphological measurements.
Main Results:
- Organ slice models enhance the focus on clinical relevance of drug side effects.
- Dose-response studies help identify risky drug concentrations for humans.
- Combined profiling and functional measurements aid in defining species differences and sensitivity.
Conclusions:
- Human organ slice studies bridge the gap between animal data and human relevance.
- These models are valuable for identifying drug-induced injury mechanisms in humans.
- Organ slice models expand the scope of translational research in drug safety assessment.
