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Uhr K, Prager-van der Smissen WJ, Heine AA, et al. Understanding drugs in breast cancer through drug sensitivity screening. Springerplus. 2015;4:611doi: 10.1186/s40064-015-1406-8.
Uhr, K., Prager-van der Smissen, W. J., Heine, A. A., Ozturk, B., Smid, M., Göhlmann, H. W., Jager, A., Foekens, J. A., & Martens, J. W. (2015). Understanding drugs in breast cancer through drug sensitivity screening. SpringerPlus, 4611. https://doi.org/10.1186/s40064-015-1406-8
Uhr, Katharina, et al. "Understanding drugs in breast cancer through drug sensitivity screening." SpringerPlus vol. 4 (2015): 611. doi: https://doi.org/10.1186/s40064-015-1406-8
Uhr K, Prager-van der Smissen WJ, Heine AA, Ozturk B, Smid M, Göhlmann HW, Jager A, Foekens JA, Martens JW. Understanding drugs in breast cancer through drug sensitivity screening. Springerplus. 2015 Oct 15;4:611. doi: 10.1186/s40064-015-1406-8. eCollection 2015. PMID: 26543746; PMCID: PMC4628005.
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Springerplus. 2015 Oct 15;4:611. doi: 10.1186/s40064-015-1406-8. eCollection 2015.

Understanding drugs in breast cancer through drug sensitivity screening.

SpringerPlus

Katharina Uhr, Wendy J C Prager-van der Smissen, Anouk A J Heine, Bahar Ozturk, Marcel Smid, Hinrich W H Göhlmann, Agnes Jager, John A Foekens, John W M Martens

Affiliations

  1. Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Postbus 2040, 's-Gravendijkwal 230, 3000 CA Rotterdam, The Netherlands.
  2. Division of Janssen Pharmaceutica, Johnson & Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
  3. Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Postbus 2040, 's-Gravendijkwal 230, 3000 CA Rotterdam, The Netherlands.

PMID: 26543746 PMCID: PMC4628005 DOI: 10.1186/s40064-015-1406-8

Abstract

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 IC50 values and thus grouped together when the cell lines were hierarchically clustered based on IC50 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 IC50 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.

Keywords: Breast cancer; Cell line; Drugs; Pathway; Screening; Subtype

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