Molekulare Mechanismen der Autophagie im duktalen Pankreaskarzinom-Modulation von Autophagie zur Behandlung vom Pankreaskarzinom

• Antragstellerin: Dr. Claudia Nitsche
• Fachliche Zuordnung: Gastroenterologie
• Förderung: Förderung von 2010 bis 2014
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 169802457

Pancreatic cancer is a highly malignant disease in which mortality equals incidence and prevalence. Underlying mechanisms causing the highly malignant growth pattern are barely understood, as are the reasons for resistance to conventional chemotherapy. Autophagy is a lysosomal degradation pathway maintaining the energy and nutrition status of the cell under stress conditions. Autophagy can possibly decrease apoptosis and thus increase the resistance of tumor cells towards chemotherapy. It can also increase the survival of cancer cells under conditions of starvation and low vascularsisation. On the other hand, excessive autophagy can mediate cell death. Increased expression of LC3 (an autophagy marker) in pancreatic cancer is correlated to a poor outcome. The underlying mechanism is unknown and needs to be unraveled. The aim of this research proposal is to elucidate the role and signaling mechanisms of autophagy in pancreatic cancer. Our preliminary data suggest that autophagy functions as a pro-survival mechanism on the cellular level in pancreatic cancer suggesting it as a potential treatment target. Understanding the underlying signaling mechanism is crucial for developing new therapeutic strategies. Pathways closely related to autophagy and therefore excellent targets for anti-cancer regimes are the mTOR and the Akt/PKB pathways. Inhibition of autophagy greatly increases the effect of Akt inhibition. This also suggests that inhibition of autophagy could increase the effect of new therapeutic approaches targeting the mTOR or PI3K Akt pathway, and hereby lead to increased survival of patients with pancreatic cancer.

• DFG-Verfahren: Sachbeihilfen
• Beteiligte Person: Professorin Dr. Julia Mayerle