PakaNostra

Early stages of pancreatic tumors often cause no symptoms, while later-stage symptoms are often nonspecific. Pancreatic cancer is therefore usually only discovered at an advanced stage, when the prognosis is already poor, since standard therapies do not bring any improvement. In cooperation with immatics, Bayer Pharma AG, EPO, Hamburg Haematopathology and the University of Marburg, the NMI is developing strategies for identifying and validating new target proteins for the treatment of pancreatic tumors. In addition, reliable test systems for early diagnosis are to be established.

The project group aims to develop new therapeutic approaches for pancreatic carcinomas that have been difficult to treat up to now. With innovative research and development projects in the companies involved, meaningful test systems in vitro and in vivo as well as alternative therapy concepts are made available. By involving academic partners and a large pharmaceutical company, a considerable part of the pharmaceutical value chain can be covered, starting with target identification, novel RNA interference technologies and assay development through to drug discovery. The novel ENTRACE technology for generating RNAi libraries is applied to convert mRNA isolated from tumor tissue into shRNA after transcribing into cDNA through several enzymatic steps. The resulting transcriptome-wide shRNA library is then screened for its influence on the survival of pancreatic tumor cells. A new mouse xenograft model is established from freshly resected pancreatic carcinoma samples from patients, which represents the behavior of pancreatic carcinoma in vivo very well. The model is suitable for both target validation and substance testing. In a further approach, isogenic cell systems are produced that depict different stages of tumor development in a genetically defined background. This is achieved through the immortalization and subsequent stepwise transformation of a primary normal parental cell with various oncogenes. All technologies will be integrated into the target identification concept for therapeutic application. The expression of the found hits is checked at mRNA and protein level, which is followed by a functional validation phase.