Characterization of pancreatic neuroendocrine tumors for tumor detection and development of new therapies

• Applicant: Privatdozent Dr. Simon Schimmack
• Subject Area: General and Visceral Surgery
• Term: from 2011 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 202188001

Pancreatic neuroendocrine tumors (pNETs) are a rare subset of pancreatic tumors, but their incidence is rising during the last three decades. Disappointingly, there has been no improvement in mean overall survival during this time. A critical issue is late diagnosis due to failure to identify symptoms or to establish the biochemical diagnosis, with the result that 60-80% of NETs are metastatic when identified. The biological behavior of pNETS varies from well differentiated tumors through to the very aggressive poorly differentiated endocrine carcinoma which have a survival as poor as that of pancreatic adenocarcinoma. However, the malignant potential cannot be predicted by histological appearance and proliferation rate is currently the only useful predictor of clinical outcome. Radical surgery is the only curative treatment for pNETs, while medical treatments including somatostatin analogs, interferon, chemotherapy, and receptor radionuclide therapy are effective only in a portion of patients with progressive disease. Little is known about the molecular pathogenesis of pNETs. The aim of this grant is to characterize neuroendocrine tumors of the pancreas to develop new therapies; in particular this research will describe tumor biology, tumor environment, and tumor specific signal pathways. This project will also identify differences between functional and non-functional tumors, and between local and metastatic tumors. Specifically, the characterization of different expressed proteins will be related to prognosis and spread. These aims will be realized in four stages: (1) High-throughput gene expression analysis to identify alterations in gene expression (confirmed with PCR); (2) micro-RNA expression analysis; (3) a proteomic screen and subsequent quantification; (4) and finally we will search for these selective proteins in blood of our patients to find diagnostic, prognostic and therapeutic markers.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Irvin Modlin, Ph.D.