Überlebensstudie am transgenen Tumormausmodell des Pankreaskarzinoms bei Chemotherapie mit Gemcitabine und additiver Aspirinapplikation.

Pancreatic cancer is a highly malignant disease with a poor prognosis. Every year almost 14.000 people in Germany fall ill with a ductal adenocarcinoma of the pancreas, which is about 3 percent of the total cancer diseases in Germany, and on the fourth position of cancer diseases in men and on the fifth position of cancer diseases in women [2]. So far, the only chance for healing is the surgical R0-resection. In total, the 5-year survival rate is less than 2 percent [64]. Since pancreatic cancer has an extremely poor prognosis and the therapeutic options of chemotherapy which are available are significantly prolonging survival but are still little promising. Therefor the development of new therapy approaches is highly relevant [28]. In 2003 the research group of Dave Tuveson developed a transgenic mouse model of pancreatic cancer, which simulates the carcinogenesis, the cancer increase and way of metastasis similar to human beings [40]. Hereby a research of new therapies in vivo has become possible. In our research group a very promising approach with enalapril and aspirin as chemoprevention of pancreatic cancer was established and lead to a significant slowdown and partial suppression of cancer increase [27]. In this thesis the effect of an additive aspirin therapy to the standard gemcitabine chemotherapy on the survival of the Pdx-1-Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+-mice was analyzed in a cancer therapy approach. Aspirin did not prolonged the survival (200 vs. 190 days; p=0,09) in comparison to gemcitabine chemotherapy. An impact on the expression of relevant target proteins like NF-kB compared to the preventive approach could not be proven. The additive aspirin therapy has successfully been tested in a prophylactic approach in a tumor-mouse-model of pancreatic cancer. If this prophylactic therapy is also effective in human beings remains unclear.