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Published on: June 17, 2022
Lymphoma and Leukemia Cell Vulnerabilities and Resistance Identified by Compound Library Screens
Katarzyna Tomska1,2, Sebastian Scheinost3, Jarno Kivioja4
1Department of Molecular Therapy in Hematology and Oncology, DKFZ & NCT Heidelberg, Heidelberg, Germany.
Abstract:
Response to anticancer agents is often restricted to subsets of patients. Recognition of factors underlying this heterogeneity and identification of biomarkers associated with response to drugs would greatly improve the efficacy of drug treatment. Platforms that can comprehensively map cellular response to compounds in high-throughput provide a unique tool to identify associated biomarkers and provide hypotheses for mechanisms underlying variable response. Such screens can be performed on cell lines and short-term cultures of primary cells to take advantage of the respective models' strength, which include, e.g., the ability to silence genes or introduce somatic mutations to cell lines. Cohorts of patient samples represent the natural diversity of cancers, including rarer mutations and combinatorial patterns of mutations that are often absent from existing cell lines. We here summarize a simple and scalable method for the measurement of viability after drug exposure based on ATP measurements as a surrogate for viability, which we use to measure and understand drug response in cell lines and primary cells.
Insights
Identifying biomarkers for anticancer drug response is crucial for personalized medicine. This study presents a scalable ATP-based viability assay to understand drug response in cell lines and primary cells, aiding biomarker discovery.
Area of Science:
- Oncology
- Pharmacology
- Biomarker Discovery
Background:
- Patient response to anticancer agents varies significantly, necessitating identification of predictive biomarkers.
- Understanding drug response heterogeneity is key to improving cancer treatment efficacy.
- High-throughput screening platforms are vital for identifying biomarkers and elucidating drug response mechanisms.
Purpose of the Study:
- To present a simple, scalable method for measuring cellular viability after drug exposure.
- To utilize this method for understanding drug response in both cell lines and primary cells.
- To facilitate the discovery of biomarkers associated with variable drug responses.
Main Methods:
- Employs adenosine triphosphate (ATP) measurements as a surrogate for cellular viability.
- Applies a high-throughput screening approach to assess drug response.
- Utilizes both cancer cell lines and short-term cultures of primary cells.
Main Results:
- Demonstrates a scalable method for quantifying drug-induced changes in cellular viability.
- Provides a framework for comprehensive mapping of cellular response to various compounds.
- Enables the study of drug response across diverse cancer models, including patient-derived samples.
Conclusions:
- The developed ATP-based viability assay is a valuable tool for drug response assessment.
- This method supports the identification of biomarkers and mechanistic insights into treatment variability.
- Enhances the potential for personalized anticancer drug selection and improved treatment outcomes.
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