PakaNostra

The project consortium has the aim to develop new treatment options for difficult-to-treat pancreatic carcinoma. Applying innovative research and development activities the participating companies will develop reliable test systems in vitro and in vivo as well as alternative therapeutic approaches. With the integration of academic partners and a big pharma company the PakaNostra consortium represents a considerable part of the pharma value chain, starting with target identification using innovative RNAi technologies and assay development up to drug discovery.
The new ENTRACE-technology for generation of RNAi-libraries is applied to convert tumour-derived mRNA into shRNA using different enzymatic steps. Subsequently, the transcriptome-wide shRNA library is screened for its impact on survival of pancreatic tumour cells.
Moreover, from freshly resected pancreatic carcinoma tissue a new xenograft model will be established in mice, representing in vivo growth of pancreatic carcinoma. This model will be used for target validation as well as for drug testing. In an additional approach, isogenic cell lines representing different stages of tumour development are generated. At this, primary cells are initially immortalised and then stepwise transformed using different oncogenes. All technologies are integrated in target identification for therapeutic use. Hits identified will be validated on mRNA and protein-level with subsequent functional validation.