Identification of signaling pathways related to drug efficacy in hepatocellular carcinoma via integration of phosphoproteomic, genomic and clinical data.
Hepatocellular Carcinoma (HCC) is one of the leading causes of death worldwide, with only a handful of treatments effective in unresectable HCC. Most of the clinical trials for HCC using new generation interventions (drug-targeted therapies) have poor efficacy whereas just a few of them show some promising clinical outcomes [1]. This is amongst the first studies where the mode of action of some of the compounds extensively used in clinical trials is interrogated on the phosphoproteomic level, in an attempt to build predictive models for clinical efficacy. Signaling data are combined with previously published gene expression and clinical data within a consistent framework that identifies drug effects on the phosphoproteomic level and translates them to the gene expression level. The interrogated drugs are then correlated with genes differentially expressed in normal versus tumor tissue, and genes predictive of patient survival. Although the number of clinical trial results considered is small, our approach shows potential for discerning signaling activities that may help predict drug efficacy for HCC.
Department of Mechanical Engineering, National Technical University of Athens, 15780 Zografou, and with ProtATonce Ltd, 15343 Athens, Greece.
Ioannis N
IN
Melas
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and the Center for Cell Decision Processes, Massachusetts Institute of Technology and Harvard Medical School, Boston, Massachusetts, USA.
Douglas A
DA
Lauffenburger
Department of Mechanical Engineering, National Technical University of Athens, 15780 Zografou, and with ProtATonce Ltd, 15343 Athens, Greece.
Leonidas G
LG
Alexopoulos