Cancer is often characterized as a disease of signal transduction pathways, since it is frequently associated with inappropriate activation of such pathways. Indeed, new therapeutic approaches in cancer therapy, such as Herceptin, frequently target signaling pathway components to revert their pathophysiological aberrations. Most oncogenic pathways have been highly conserved throughout evolution with Drosophila representing a particularly powerful genetic model for the analysis of such signaling cascades. These cancer pathways include Wnt, Notch, Hippo and JAK/STAT pathways. The analysis of signaling pathways in Drosophila is facilitated by the availability of a broad range of genetic tools, a completely sequenced genome and the availability of genome-wide collections of RNAi reagents. Within this project, we will establish high-throughput cell-based assays for regulators of the major developmental oncogenic signaling pathways. Cell-based assays for signaling pathways will be screened using genome-wide RNAi and small molecule compound libraries to identify new components, regulators and targets. Suppressor/enhancer screens in cultured cells will be used to identify small molecular compounds that interfere with the activity of specific signaling pathways and in vivo models of signaling pathways will be established to test the activity of drugs using developmental and tumorogenic phenotypes. By integrating and standardizing data from most important cancer relevant signaling pathways and combining them with powerful bioinformatics tools, we expect to get highly validated information on possible drug targets and lead substances. The collaborative project integrates recent technological advances, such as genome-wide RNAi libraries for cell-based and in vivo assay models that were developed by the participants, as well as computational approaches and databases to integrate and disseminate the information obtained during the project.