The NCI transcriptional pharmacodynamics workbench: A tool to examine dynamic expression profiling of therapeutic response in the NCI-60 cell line panel

Anne Monks, Yingdong Zhao, Curtis Hose, Hossein Hamed, Julia Krushkal, Jianwen Fang, Dmitriy Sonkin, Alida Palmisano, Eric Polley, Laura K. Fogli, Mariam M. Konate, Sarah B. Miller, Melanie A. Simpson, Andrea Regier Voth, Ming Chung Li, Erik Harris, Xiaolin Wu, John W. Connelly, Annamaria Rapisarda, Beverly A. TeicherRichard Simon, James H. Doroshow

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The intracellular effects and overall efficacies of anticancer therapies can vary significantly by tumor type. To identify patterns of drug-induced gene modulation that occur in different cancer cell types, we measured gene-expression changes across the NCI-60 cell line panel after exposure to 15 anticancer agents. The results were integrated into a combined database and set of interactive analysis tools, designated the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), that allows exploration of gene-expression modulation by molecular pathway, drug target, and association with drug sensitivity. We identified common transcriptional responses across agents and cell types and uncovered gene-expression changes associated with drug sensitivity. We also demonstrated the value of this tool for investigating clinically relevant molecular hypotheses and identifying candidate biomarkers of drug activity. The NCI TPW, publicly available at https://tpwb.nci.nih. gov, provides a comprehensive resource to facilitate understanding of tumor cell characteristics that define sensitivity to commonly used anticancer drugs. Significance: The NCI Transcriptional Pharmacodynamics Workbench represents the most extensive compilation to date of directly measured longitudinal transcriptional responses to anticancer agents across a thoroughly characterized ensemble of cancer cell lines.

Original languageEnglish (US)
Pages (from-to)6807-6817
Number of pages11
JournalCancer Research
Volume78
Issue number24
DOIs
StatePublished - Dec 15 2018
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Monks, A., Zhao, Y., Hose, C., Hamed, H., Krushkal, J., Fang, J., Sonkin, D., Palmisano, A., Polley, E., Fogli, L. K., Konate, M. M., Miller, S. B., Simpson, M. A., Voth, A. R., Li, M. C., Harris, E., Wu, X., Connelly, J. W., Rapisarda, A., ... Doroshow, J. H. (2018). The NCI transcriptional pharmacodynamics workbench: A tool to examine dynamic expression profiling of therapeutic response in the NCI-60 cell line panel. Cancer Research, 78(24), 6807-6817. https://doi.org/10.1158/0008-5472.CAN-18-0989