title: Enhancing reproducibility in cancer drug screening: how do we move forward?
abstract: Large-scale pharmacogenomic high-throughput screening (HTS) studies hold great potential for generating robust genomic predictors of drug response. Two recent large-scale HTS studies have reported results of such screens, revealing several known and novel drug sensitivities and biomarkers. Subsequent evaluation, however, found only moderate interlaboratory concordance in the drug response phenotypes, possibly due to differences in the experimental protocols used in the two studies. This highlights the need for community-wide implementation of standardized assays for measuring drug response phenotypes so that the full potential of HTS is realized. We suggest that the path forward is to establish best practices and standardization of the critical steps in these assays through a collective effort to ensure that the data produced from large-scale screens would not only be of high intrastudy consistency, so that they could be replicated and compared successfully across multiple laboratories.
authors.affiliation: Section of Medical Oncology, Yale University School of Medicine; Yale Cancer Center, Yale University, New Haven, Connecticut;
authors.forename: Christos
authors.initials: C
authors.lastname: Hatzis
authors.affiliation: Princess Margaret Cancer Centre, University Health Network; Faculty of Medicine;
authors.forename: Philippe L
authors.initials: PL
authors.lastname: Bedard
authors.affiliation: Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark;
authors.forename: Nicolai J
authors.initials: NJ
authors.lastname: Birkbak
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School;
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Beck
authors.affiliation: Department of Biostatistics and Computational Biology and Center for Cancer Computational Biology; Department of Radiation Oncology and Radiology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Hugo J W L
authors.initials: HJ
authors.lastname: Aerts
authors.forename: David F
authors.initials: DF
authors.lastname: Stem
authors.affiliation: Department of Pathology, Yale University School of Medicine; Yale Cancer Center, Yale University, New Haven, Connecticut;
authors.forename: David F
authors.initials: DF
authors.lastname: Stern
authors.affiliation: National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas; State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Schools of Life Sciences and Pharmacy, Fudan University, Shanghai; and Zhanjiang Center for Translational Medicine, Shanghai, China.
authors.forename: Leming
authors.initials: L
authors.lastname: Shi
authors.affiliation: Georgetown University Medical Center, Washington, DC;
authors.forename: Robert
authors.initials: R
authors.lastname: Clarke
authors.affiliation: Department of Biostatistics and Computational Biology and Center for Cancer Computational Biology; Department of Cancer Biology, Dana-Farber Cancer Institute;
authors.forename: John
authors.initials: J
authors.lastname: Quackenbush
authors.affiliation: Princess Margaret Cancer Centre, University Health Network; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; bhaibeka@uhnresearch.ca.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Haibe-Kains
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods*; D004354:Drug Screening Assays, Antitumor / Q000379:methods* / Q000592:standards*; D057166:High-Throughput Screening Assays / Q000379:methods / Q000592:standards; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods / Q000592:standards; D015203:Reproducibility of Results
chemical_list: D000970:Antineoplastic Agents