Display Settings:

Format

Send to:

Choose Destination
Sci Transl Med. 2011 Aug 17;3(96):96ra77. doi: 10.1126/scitranslmed.3001318.

Discovery and preclinical validation of drug indications using compendia of public gene expression data.

Author information

  • 1Division of Systems Medicine, Department of Pediatrics, Stanford University School of Medicine, 251 Campus Drive, Stanford, CA 94305-5415, USA.

Erratum in

  • Sci Transl Med. 2011 Sep 28;3(102):102er7.

Abstract

The application of established drug compounds to new therapeutic indications, known as drug repositioning, offers several advantages over traditional drug development, including reduced development costs and shorter paths to approval. Recent approaches to drug repositioning use high-throughput experimental approaches to assess a compound's potential therapeutic qualities. Here, we present a systematic computational approach to predict novel therapeutic indications on the basis of comprehensive testing of molecular signatures in drug-disease pairs. We integrated gene expression measurements from 100 diseases and gene expression measurements on 164 drug compounds, yielding predicted therapeutic potentials for these drugs. We recovered many known drug and disease relationships using computationally derived therapeutic potentials and also predict many new indications for these 164 drugs. We experimentally validated a prediction for the antiulcer drug cimetidine as a candidate therapeutic in the treatment of lung adenocarcinoma, and demonstrate its efficacy both in vitro and in vivo using mouse xenograft models. This computational method provides a systematic approach for repositioning established drugs to treat a wide range of human diseases.

Comment in

PMID:
21849665
[PubMed - indexed for MEDLINE]
PMCID:
PMC3502016
Free PMC Article

Images from this publication.See all images (4)Free text

Figure 1
Figure 2
Figure 3
Figure 4
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk