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Understanding drugs in breast cancer through drug sensitivity screening
With substantial numbers of breast tumors showing or acquiring treatment resistance, it is of utmost importance to develop new agents for the treatment of the disease, to know their effectiveness against breast cancer and to understand their relationships with other drugs to best assign the right dr...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628005/ https://www.ncbi.nlm.nih.gov/pubmed/26543746 http://dx.doi.org/10.1186/s40064-015-1406-8 |
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author | Uhr, Katharina Prager-van der Smissen, Wendy J. C. Heine, Anouk A. J. Ozturk, Bahar Smid, Marcel Göhlmann, Hinrich W. H. Jager, Agnes Foekens, John A. Martens, John W. M. |
author_facet | Uhr, Katharina Prager-van der Smissen, Wendy J. C. Heine, Anouk A. J. Ozturk, Bahar Smid, Marcel Göhlmann, Hinrich W. H. Jager, Agnes Foekens, John A. Martens, John W. M. |
author_sort | Uhr, Katharina |
collection | PubMed |
description | With substantial numbers of breast tumors showing or acquiring treatment resistance, it is of utmost importance to develop new agents for the treatment of the disease, to know their effectiveness against breast cancer and to understand their relationships with other drugs to best assign the right drug to the right patient. To achieve this goal drug screenings on breast cancer cell lines are a promising approach. In this study a large-scale drug screening of 37 compounds was performed on a panel of 42 breast cancer cell lines representing the main breast cancer subtypes. Clustering, correlation and pathway analyses were used for data analysis. We found that compounds with a related mechanism of action had correlated IC(50) values and thus grouped together when the cell lines were hierarchically clustered based on IC(50) values. In total we found six clusters of drugs of which five consisted of drugs with related mode of action and one cluster with two drugs not previously connected. In total, 25 correlated and four anti-correlated drug sensitivities were revealed of which only one drug, Sirolimus, showed significantly lower IC(50) values in the luminal/ERBB2 breast cancer subtype. We found expected interactions but also discovered new relationships between drugs which might have implications for cancer treatment regimens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-015-1406-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4628005 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-46280052015-11-05 Understanding drugs in breast cancer through drug sensitivity screening Uhr, Katharina Prager-van der Smissen, Wendy J. C. Heine, Anouk A. J. Ozturk, Bahar Smid, Marcel Göhlmann, Hinrich W. H. Jager, Agnes Foekens, John A. Martens, John W. M. Springerplus Research With substantial numbers of breast tumors showing or acquiring treatment resistance, it is of utmost importance to develop new agents for the treatment of the disease, to know their effectiveness against breast cancer and to understand their relationships with other drugs to best assign the right drug to the right patient. To achieve this goal drug screenings on breast cancer cell lines are a promising approach. In this study a large-scale drug screening of 37 compounds was performed on a panel of 42 breast cancer cell lines representing the main breast cancer subtypes. Clustering, correlation and pathway analyses were used for data analysis. We found that compounds with a related mechanism of action had correlated IC(50) values and thus grouped together when the cell lines were hierarchically clustered based on IC(50) values. In total we found six clusters of drugs of which five consisted of drugs with related mode of action and one cluster with two drugs not previously connected. In total, 25 correlated and four anti-correlated drug sensitivities were revealed of which only one drug, Sirolimus, showed significantly lower IC(50) values in the luminal/ERBB2 breast cancer subtype. We found expected interactions but also discovered new relationships between drugs which might have implications for cancer treatment regimens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-015-1406-8) contains supplementary material, which is available to authorized users. Springer International Publishing 2015-10-15 /pmc/articles/PMC4628005/ /pubmed/26543746 http://dx.doi.org/10.1186/s40064-015-1406-8 Text en © Uhr et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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. |
spellingShingle | Research Uhr, Katharina Prager-van der Smissen, Wendy J. C. Heine, Anouk A. J. Ozturk, Bahar Smid, Marcel Göhlmann, Hinrich W. H. Jager, Agnes Foekens, John A. Martens, John W. M. Understanding drugs in breast cancer through drug sensitivity screening |
title | Understanding drugs in breast cancer through drug sensitivity screening |
title_full | Understanding drugs in breast cancer through drug sensitivity screening |
title_fullStr | Understanding drugs in breast cancer through drug sensitivity screening |
title_full_unstemmed | Understanding drugs in breast cancer through drug sensitivity screening |
title_short | Understanding drugs in breast cancer through drug sensitivity screening |
title_sort | understanding drugs in breast cancer through drug sensitivity screening |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628005/ https://www.ncbi.nlm.nih.gov/pubmed/26543746 http://dx.doi.org/10.1186/s40064-015-1406-8 |
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