"Suppression of enzymes required for progression of lung cancer: we propose to combine an elegant genetically engineered mouse model (GEMM) of lung cancer with an in vivo RNAi screening approach in order to functionally identify a) biomarkers of early lung cancer development and b) candidate therapeutic targets whose activities are specifically required for the transition from benign to malignant disease. We will use emerging RNA sequencing technology to identify changes in gene expression associate with early cancer progression in GEMMs of lung cancer and then select targets for RNAi suppression based on a stringent set of selection criteria aimed at zeroing in on potential drug targets, i.e.. proteins with enzymatic activity of any druggable nature that increase with tumour progression. We will then generate focused libraries of shRNAs to suppress expression of selected targets and screen their efficacy in vivo using a cunning ""drop-out"" screening method. We will then subject our best candidates to rigorous validation in order to assess their suitability as therapuetic targets in the context of human lung cancer."
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