title: Assessing Combinational Drug Efficacy in Cancer Cells by Using Image-based Dynamic Response Analysis.
abstract: The landscape of translational research has been shifting toward drug combination therapies. Pairing of drugs allows for more types of drug interaction with cells. In order to accurately and comprehensively assess combinational drug efficacy, analytical methods capable of recognizing these alternative reactions will be required to prioritize those drug candidates having better chances of delivering appreciable therapeutic benefits. Traditional efficacy measures are primarily based on the "extent" of drug inhibition, which is the percentage of cells being killed after drug exposure. Here, we introduce a second dimension of evaluation criterion, speed of killing, based on a live cell imaging assay. This dynamic response trajectory approach takes advantage of both "extent" and "speed" information and uncovers synergisms that would otherwise be missed, while also generating hypotheses regarding important mechanistic modes of drug action.
authors.affiliation: Center for Bioinformatics and Genomic Systems Engineering, Texas A&M Engineering Experiment Station, Texas A&M University, College Station, TX, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Sima
authors.affiliation: Center for Bioinformatics and Genomic Systems Engineering, Texas A&M Engineering Experiment Station, Texas A&M University, College Station, TX, USA.
authors.forename: Jianping
authors.initials: J
authors.lastname: Hua
authors.affiliation: Center for Bioinformatics and Genomic Systems Engineering, Texas A&M Engineering Experiment Station, Texas A&M University, College Station, TX, USA.
authors.forename: Milana
authors.initials: M
authors.lastname: Cypert
authors.affiliation: College of Veterinary Medicine, Texas A&M University, College Station, TX, USA.
authors.forename: Tasha
authors.initials: T
authors.lastname: Miller
authors.affiliation: College of Veterinary Medicine, Texas A&M University, College Station, TX, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Wilson-Robles
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Trent
authors.affiliation: Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX, USA.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Dougherty
authors.affiliation: Center for Bioinformatics and Genomic Systems Engineering, Texas A&M Engineering Experiment Station, Texas A&M University, College Station, TX, USA.; Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Bittner
keywords: cell imaging; combinational drug; drug response; dynamics; synergism