In the EU FP7 project CancerPathways we aim to identify novel targets and drugs for cancer treatment using Drosophila as model organism. Drosophila has many unique characteristics, representing a particularly powerful genetic model for the analysis of signaling cascades by high-throughput approaches. Most oncogenic pathways have been highly conserved throughout evolution and of the known cancer genes, over 90% are present in Drosophila.
The aberrant activation of signaling pathways is causal to cancer development. Understanding these pathways will enable to identify novel targets for cancer drugs. Furthermore, testing of small molecular compounds for their potency to modify signaling pathway activity will afford the identification of potential novel therapeutic agents. In order to perform screenings for targets and molecules in a high-throughput format, robust bioassays are necessary.
Our strategy to identify target genes is to use high-throughput genome-wide RNA interference (RNAi) screens in cultured Drosophila cells in vitro and Drosophila flies in vivo. The recent discovery of RNAi allows the systematic knockdown of all genes in an organism. RNAi experiments in Drosophila are facilitated by a low genetic redundancy and highly efficient target gene knockdown by long double-stranded RNAs. Data will be standardized and integrated with powerful bioinformatic tools. The information obtained during the project will be made publicly available and disseminated in databases.
The CancerPathways project is divided into 5 scientific work packages and is based on high-throughput bioassays in cultured Drosophila cells in vitro and Drosophila flies in vivo. Bioassays will be developed and optimized in WP1 (High-throughput bioassay development) and implemented in WP2 (High-throughput cell-based screens using RNAi and chemical libraries) and WP3 (In vivo RNAi library and screening), respectively. The identified targets and lead compounds will then be validated in WP4 (In vivo validation of identified targets and lead compounds). Bioinformatic tools to process and analyze the generated high-throughput data are being developed in WP5 (Bioinformatics and dissemination). Our final goal is to generate a database that contains phenotype information from cell-based and in vivo screens.