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
Rok vydání: 2019
Předmět:
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