Title: Identification of Disease-Relevant Genes for Molecularly-Targeted Drug Discovery
Volume: 12
Issue: 1
Author(s): G. Kauselmann, A. Dopazo and W. Link
Affiliation:
Keywords:
Analogue sensitive kinase alleles, chemical genetics, genetically engineered mice, high content screening, imatinib, target discovery, target validation, Calcium calmodulin, Chronic myelogenous leukemia, Central nervous system, Embryonic stem cells, Green fluorescent protein, loss of heterozygosity, RNA interference
Abstract: The current paradigm for cancer therapy is undergoing a change from non-specific cytotoxic agents to more specific approaches based on unique molecular features of cancer cells. The identification and validation of disease relevant targets are crucial for the development of molecularly targeted anticancer therapies. Advances in our understanding of the molecular basis of cancer together with novel approaches to interfere with signal transduction pathways have opened new horizons for anticancer target discovery. In particular, the image-based large scale analysis of cellular phenotypes that arise from genetic or chemical perturbations paved the way for the identification and validation of disease relevant molecular targets independent of preconceived notions of mechanistic relationships. In addition, novel and sophisticated techniques of genome manipulation allow for the use of mouse models that faithfully recapitulate critical elements of human cancer for target validation in vivo. We believe that these advances will translate into more and better validated drug targets.
