An unbiased metric of antiproliferative drug effect in vitro

Conventional metrics for assessing antiproliferative drug effect have time-dependent biases that may skew results. The drug-induced proliferation rate can be used as an alternative metric for accurate and reproducible assessment of drug performance. In vitro cell proliferation assays are widely used...

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Veröffentlicht in:Nature methods 2016-06, Vol.13 (6), p.497-500
Hauptverfasser: Harris, Leonard A, Frick, Peter L, Garbett, Shawn P, Hardeman, Keisha N, Paudel, B Bishal, Lopez, Carlos F, Quaranta, Vito, Tyson, Darren R
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Sprache:eng
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Zusammenfassung:Conventional metrics for assessing antiproliferative drug effect have time-dependent biases that may skew results. The drug-induced proliferation rate can be used as an alternative metric for accurate and reproducible assessment of drug performance. In vitro cell proliferation assays are widely used in pharmacology, molecular biology, and drug discovery. Using theoretical modeling and experimentation, we show that current metrics of antiproliferative small molecule effect suffer from time-dependent bias, leading to inaccurate assessments of parameters such as drug potency and efficacy. We propose the drug-induced proliferation (DIP) rate, the slope of the line on a plot of cell population doublings versus time, as an alternative, time-independent metric.
ISSN:1548-7091
1548-7105
DOI:10.1038/nmeth.3852