This project will investigate the mechanisms resulting in hypersecretion by neuroendocrine tumors, as well as identify the changes to the proteins secreted by such tumors. Identified candidate targets for modulation of hypersecretion could generate improved therapies. Furthermore, the resulting identification of candidate secretory protein biomarkers could become the basis of better diagnostic and prognostic markers.
Cancer is the second leading cause of death in the developed world and despite intense efforts to reduce its mortality rate, only modest progress has been made. Particularly problematic are cancers derived from endocrine tumors. Because endocrine tumors arise from hormone-producing cells, the tumor itself can over-produce hormones that can cause serious illness and complications. These neuroendocrine tumors are very difficult to diagnose. The existing treatments are ineffective in late stage tumors. Therefore, there is an urgent need to improve diagnosis and develop more effective therapies against neuroendocrine tumors. The aggressiveness and poor prognosis of these tumors appears to be linked to the high level of protein secretion by the tumor.
The main objective of this collaborative project is to investigate the mechanisms resulting in neuroendocrine tumor hyper-secretion, and to identify and validate diagnostic and prognostic biomarkers for clinical treatment of neuroendocrine tumors. A diversity of approaches using in vitro cell lines as well as neuroendocrine tumor tissues are being used to identify and validate candidate protein biomarkers. The well-established large-scale Caprion proteomics platform will identify candidate protein biomarkers that display reproducible, condition-specific expression changes. To date proteomic analyses on cell lines and neuroendocrine tumors have led to the identification of more than two thousand differentially expressed proteins. Candidate protein biomarkers were selected and validation of these candidate proteins is currently underway.
Impact on the drug discovery process