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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...

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Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2015
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
Descripción
Sumario: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.