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Nat Commun. 2017 Jul 12;8:16022. doi: 10.1038/ncomms16022.

Reversal of cancer gene expression correlates with drug efficacy and reveals therapeutic targets.

Author information

1
Department of Pediatrics, Institute for Computational Health Sciences, University of California, San Francisco, 550 16th Street, San Francisco, California 94143, USA.
2
Department of Surgery, Asian Liver Center, School of Medicine, Stanford University, 1201 Welch Road, Stanford, California 94305, USA.
3
Biomedical HPC Technology Research Center, Korea Institute of Science and Technology Information, 245, Daehak-ro, Yuseong-gu, Daejeon 34141, South Korea.

Abstract

The decreasing cost of genomic technologies has enabled the molecular characterization of large-scale clinical disease samples and of molecular changes upon drug treatment in various disease models. Exploring methods to relate diseases to potentially efficacious drugs through various molecular features is critically important in the discovery of new therapeutics. Here we show that the potency of a drug to reverse cancer-associated gene expression changes positively correlates with that drug's efficacy in preclinical models of breast, liver and colon cancers. Using a systems-based approach, we predict four compounds showing high potency to reverse gene expression in liver cancer and validate that all four compounds are effective in five liver cancer cell lines. The in vivo efficacy of pyrvinium pamoate is further confirmed in a subcutaneous xenograft model. In conclusion, this systems-based approach may be complementary to the traditional target-based approach in connecting diseases to potentially efficacious drugs.

PMID:
28699633
PMCID:
PMC5510182
DOI:
10.1038/ncomms16022
[Indexed for MEDLINE]
Free PMC Article

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