Format

Send to

Choose Destination
Cancer Res. 2018 Dec 15;78(24):6807-6817. doi: 10.1158/0008-5472.CAN-18-0989. Epub 2018 Oct 24.

The NCI Transcriptional Pharmacodynamics Workbench: A Tool to Examine Dynamic Expression Profiling of Therapeutic Response in the NCI-60 Cell Line Panel.

Author information

1
Molecular Pharmacology Group, Frederick National Laboratory for Cancer Research sponsored by the NCI, Frederick, Maryland.
2
Biometric Research Program, Division of Cancer Treatment and Diagnosis, NCI, NIH, Rockville, Maryland.
3
Division of Cancer Treatment and Diagnosis, NCI, NIH, Bethesda, Maryland.
4
Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research sponsored by the NCI, Frederick, Maryland.
5
Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the NCI, Frederick, Maryland.
6
Division of Cancer Treatment and Diagnosis, NCI, NIH, Bethesda, Maryland. doroshoj@mail.nih.gov.
7
Center for Cancer Research, NCI, NIH, Bethesda, Maryland.

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.

PMID:
30355619
PMCID:
PMC6295263
[Available on 2019-12-15]
DOI:
10.1158/0008-5472.CAN-18-0989

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center