title: Understanding drugs in breast cancer through drug sensitivity screening.
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.
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Postbus 2040, 's-Gravendijkwal 230, 3000 CA Rotterdam, The Netherlands.
authors.forename: Katharina
authors.initials: K
authors.lastname: Uhr
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Postbus 2040, 's-Gravendijkwal 230, 3000 CA Rotterdam, The Netherlands.
authors.forename: Wendy J C
authors.initials: WJ
authors.lastname: Prager-van der Smissen
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Postbus 2040, 's-Gravendijkwal 230, 3000 CA Rotterdam, The Netherlands.
authors.forename: Anouk A J
authors.initials: AA
authors.lastname: Heine
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Postbus 2040, 's-Gravendijkwal 230, 3000 CA Rotterdam, The Netherlands.
authors.forename: Bahar
authors.initials: B
authors.lastname: Ozturk
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Postbus 2040, 's-Gravendijkwal 230, 3000 CA Rotterdam, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Smid
authors.affiliation: Division of Janssen Pharmaceutica, Johnson & Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
authors.forename: Hinrich W H
authors.initials: HW
authors.lastname: Göhlmann
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Postbus 2040, 's-Gravendijkwal 230, 3000 CA Rotterdam, The Netherlands.
authors.forename: Agnes
authors.initials: A
authors.lastname: Jager
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Postbus 2040, 's-Gravendijkwal 230, 3000 CA Rotterdam, The Netherlands.
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
authors.affiliation: 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.
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
keywords: Breast cancer; Cell line; Drugs; Pathway; Screening; Subtype