Measurement and models accounting for cell death capture hidden variation in compound response
Autor: | Aaron S. Meyer, Katrina Warner, Rui Yan, Ning Guan, Song Yi Bae, Scott Taylor |
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Rok vydání: | 2019 |
Předmět: |
Cancer Research
Programmed cell death Cell Survival Immunology Oncology and Carcinogenesis Drug development Antineoplastic Agents Apoptosis Biology Article Cell Line Cellular and Molecular Neuroscience Immune system Cell Line Tumor Humans Viability assay lcsh:QH573-671 Cancer Cell Proliferation Tumor microenvironment Tumor Cell Death Cell growth lcsh:Cytology Correction Cell Biology Cell biology Cell culture 5.1 Pharmaceuticals Cancer cell Necroptosis Biochemistry and Cell Biology Development of treatments and therapeutic interventions |
Zdroj: | Cell Death Dis Cell Death & Disease Cell Death and Disease, Vol 11, Iss 4, Pp 1-9 (2020) Cell death & disease, vol 11, iss 4 |
ISSN: | 2041-4889 |
Popis: | Cancer cell sensitivity or resistance is almost universally quantified through a direct or surrogate measure of cell number. However, compound responses can occur through many distinct phenotypic outcomes, including changes in cell growth, apoptosis, and non-apoptotic cell death. These outcomes have divergent effects on the tumor microenvironment, immune response, and resistance mechanisms. Here, we show that quantifying cell viability alone is insufficient to distinguish between these compound responses. Using an alternative assay and drug-response analysis amenable to high-throughput measurement, we find that compounds with identical viability outcomes can have very different effects on cell growth and death. Moreover, additive compound pairs with distinct growth/death effects can appear synergistic when only assessed by viability. Overall, these results demonstrate an approach to incorporating measurements of cell death when characterizing a pharmacologic response. |
Databáze: | OpenAIRE |
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