1. The NCI Transcriptional Pharmacodynamics Workbench: A Tool to Examine Dynamic Expression Profiling of Therapeutic Response in the NCI-60 Cell Line Panel
- Author
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Eric C. Polley, Mariam M. Konaté, Hossein A. Hamed, Yingdong Zhao, Dmitriy Sonkin, James H. Doroshow, Erik Harris, Richard Simon, John Connelly, Anne Monks, Beverly A. Teicher, Melanie A. Simpson, Alida Palmisano, Laura K. Fogli, Ming Chung Li, Jianwen Fang, Curtis Hose, Annamaria Rapisarda, Andrea Regier Voth, Sarah B. Miller, Xiaolin Wu, and Julia Krushkal
- Subjects
0301 basic medicine ,Therapeutic gene modulation ,Drug ,Cancer Research ,Cell type ,media_common.quotation_subject ,Antineoplastic Agents ,Computational biology ,Biology ,Deoxycytidine ,Article ,Translational Research, Biomedical ,03 medical and health sciences ,Erlotinib Hydrochloride ,0302 clinical medicine ,Cell Line, Tumor ,Biomarkers, Tumor ,Humans ,media_common ,Early Growth Response Protein 1 ,Oligonucleotide Array Sequence Analysis ,Internet ,Vorinostat ,Dose-Response Relationship, Drug ,Gene Expression Profiling ,Gemcitabine ,National Cancer Institute (U.S.) ,United States ,Gene expression profiling ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,Cell culture ,030220 oncology & carcinogenesis ,Pharmacodynamics ,Cancer cell ,Drug Screening Assays, Antitumor ,Intracellular ,Signal Transduction - 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.
- Published
- 2018