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High-Throughput Kinetic Analysis of Fractional Killing

ABSTRACT: Anti-cancer drugs and other lethal agents can induce heterogeneous cell death responses in a population of cancer cells, a phenomenon referred to as fractional killing (FK). FK is often studied on a cell-by-cell basis in response to one or a limited number of stimuli. Here, we develop and validate methods to quantify FK in a high-throughput manner using population-level time-lapse measurements and mathematical modelling. Using this approach, we find that FK is highly variable over time and that the kinetics of this process can vary substantially by drug class and cell line. Focusing on FK induced by clinical candidate inhibitors of mitogen activated protein kinase kinase (MEK) 1/2, we find that MCL1 levels are be an important determinant of FK in some but not all cell lines and that generalizable molecular models of FK are rare. These studies lay the foundation for quantitative high-throughput analyses of FK.

ORGANISM(S): Homo sapiens

PROVIDER: GSE140172 | GEO | 2019/11/11

REPOSITORIES: GEO

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