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Traditional preclinical discovery methods, particularly for target validation, poorly predict drug efficacy, causing a high attrition rate in costly late-stage clinical trials. The PREDECT consortium will focus on complex but transferable, next generation in vitro and in vivo models for breast, prostate and lung cancers. Models will be investigated for their improved potential to validate novel therapeutic targets. Known targets, in canonical pathways, will be interrogated for induction of phenotypic, proteomic and transcriptomic changes using inhibitors. A strategy of seeking a ‘dynamic reciprocity’ of concordance between the steady and perturbed states of in vitro complex cultures, tissue slices and in vivo tumour models will be pursued by systems biology analyses. Comparison with historic gene expression and genomic data from relevant clinical materials should permit the emergence of faithful models for target validation and beyond.
PREDECT is coordinated by Servier and AstraZeneca, and the managing |
