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Clinical drug response can be predicted using baseline gene expression levels and in vitro drug sensitivity in cell lines

Paul Geeleher1, Nancy J Cox2 and R Stephanie Huang1*

Author Affiliations

1 Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA

2 Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA

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Genome Biology 2014, 15:R47  doi:10.1186/gb-2014-15-3-r47

Published: 3 March 2014

Abstract

We demonstrate a method for the prediction of chemotherapeutic response in patients using only before-treatment baseline tumor gene expression data. First, we fitted models for whole-genome gene expression against drug sensitivity in a large panel of cell lines, using a method that allows every gene to influence the prediction. Following data homogenization and filtering, these models were applied to baseline expression levels from primary tumor biopsies, yielding an in vivo drug sensitivity prediction. We validated this approach in three independent clinical trial datasets, and obtained predictions equally good, or better than, gene signatures derived directly from clinical data.