title: An unbiased metric of antiproliferative drug effect in vitro.
abstract: 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.
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Center for Cancer Systems Biology at Vanderbilt, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Leonard A
authors.initials: LA
authors.lastname: Harris
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Center for Cancer Systems Biology at Vanderbilt, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Frick
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Center for Cancer Systems Biology at Vanderbilt, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Garbett
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Center for Cancer Systems Biology at Vanderbilt, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Keisha N
authors.initials: KN
authors.lastname: Hardeman
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Center for Cancer Systems Biology at Vanderbilt, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: B Bishal
authors.initials: BB
authors.lastname: Paudel
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Lopez
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Center for Cancer Systems Biology at Vanderbilt, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Vito
authors.initials: V
authors.lastname: Quaranta
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Center for Cancer Systems Biology at Vanderbilt, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Tyson
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008856:Microscopy, Fluorescence; D008962:Models, Theoretical; D008967:Molecular Biology / Q000379:methods*; D012680:Sensitivity and Specificity; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D054852:Small Molecule Libraries