Functional genomic analysis of drug sensitivity pathways to guide adjuvant strategies in breast cancer
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* Corresponding author: Charles Swanton charles.swanton@cancer.org.uk
1 Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
2 Royal Marsden Hospital, Breast Unit, Department of Medicine, Downs Road Sutton, Surrey, SM2 5PT, UK
3 Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Lyngby, Denmark
4 Children's Hospital Informatics Program at the Harvard-MIT Division of Health Sciences and Technology (CHIP@HST), Harvard Medical School, Boston, MA 02115, USA
5 Functional Genomics of Ovarian Cancer Laboratory, Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
6 Signal Transduction Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
Breast Cancer Research 2008, 10:214 doi:10.1186/bcr2159
Published: 31 October 2008Abstract
The widespread introduction of high throughput RNA interference screening technology has revealed tumour drug sensitivity pathways to common cytotoxics such as paclitaxel, doxorubicin and 5-fluorouracil, targeted agents such as trastuzumab and inhibitors of AKT and Poly(ADP-ribose) polymerase (PARP) as well as endocrine therapies such as tamoxifen. Given the limited power of microarray signatures to predict therapeutic response in associative studies of small clinical trial cohorts, the use of functional genomic data combined with expression or sequence analysis of genes and microRNAs implicated in drug response in human tumours may provide a more robust method to guide adjuvant treatment strategies in breast cancer that are transferable across different expression platforms and patient cohorts.