Functional genomic analysis of drug sensitivity pathways to guide adjuvant strategies in breast cancer

doi:10.1186/bcr2159

Breast Cancer Research

Volume 10
Issue 5

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Functional genomic analysis of drug sensitivity pathways to guide adjuvant strategies in breast cancer

Charles Swanton¹^,2 , Zoltan Szallasi³^,4 , James D Brenton⁵ and Julian Downward⁶

¹Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK

²Royal Marsden Hospital, Breast Unit, Department of Medicine, Downs Road Sutton, Surrey, SM2 5PT, UK

³Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Lyngby, Denmark

⁴Children's Hospital Informatics Program at the Harvard-MIT Division of Health Sciences and Technology (CHIP@HST), Harvard Medical School, Boston, MA 02115, USA

⁵Functional Genomics of Ovarian Cancer Laboratory, Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK

⁶Signal Transduction Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK

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Breast Cancer Research 2008, 10:214doi:10.1186/bcr2159


Published:	31 October 2008

Abstract

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.