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

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 featu...

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Autores principales: Chen, Bin, Ma, Li, Paik, Hyojung, Sirota, Marina, Wei, Wei, Chua, Mei-Sze, So, Samuel, Butte, Atul J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510182/
https://www.ncbi.nlm.nih.gov/pubmed/28699633
http://dx.doi.org/10.1038/ncomms16022
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author Chen, Bin
Ma, Li
Paik, Hyojung
Sirota, Marina
Wei, Wei
Chua, Mei-Sze
So, Samuel
Butte, Atul J.
author_facet Chen, Bin
Ma, Li
Paik, Hyojung
Sirota, Marina
Wei, Wei
Chua, Mei-Sze
So, Samuel
Butte, Atul J.
author_sort Chen, Bin
collection PubMed
description 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.
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spelling pubmed-55101822017-07-17 Reversal of cancer gene expression correlates with drug efficacy and reveals therapeutic targets Chen, Bin Ma, Li Paik, Hyojung Sirota, Marina Wei, Wei Chua, Mei-Sze So, Samuel Butte, Atul J. Nat Commun Article 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. Nature Publishing Group 2017-07-12 /pmc/articles/PMC5510182/ /pubmed/28699633 http://dx.doi.org/10.1038/ncomms16022 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Chen, Bin
Ma, Li
Paik, Hyojung
Sirota, Marina
Wei, Wei
Chua, Mei-Sze
So, Samuel
Butte, Atul J.
Reversal of cancer gene expression correlates with drug efficacy and reveals therapeutic targets
title Reversal of cancer gene expression correlates with drug efficacy and reveals therapeutic targets
title_full Reversal of cancer gene expression correlates with drug efficacy and reveals therapeutic targets
title_fullStr Reversal of cancer gene expression correlates with drug efficacy and reveals therapeutic targets
title_full_unstemmed Reversal of cancer gene expression correlates with drug efficacy and reveals therapeutic targets
title_short Reversal of cancer gene expression correlates with drug efficacy and reveals therapeutic targets
title_sort reversal of cancer gene expression correlates with drug efficacy and reveals therapeutic targets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510182/
https://www.ncbi.nlm.nih.gov/pubmed/28699633
http://dx.doi.org/10.1038/ncomms16022
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