MAPTor-Net - A Systems-Biology Approach to Personalized Treatment of Pancreatic Tumors

Pancreatic NET (pNET) comprises the most prominent subgroup group of rare neuroendocrine tumours (NET) with distinct prognostic classes, and thus diverse therapeutic regimens. Available pNET treatments include somatostatin analogues, systemic chemotherapy, and novel molecular drugs targeting receptor tyrosine kinases (Sunitinib), or the mTOR pathway (Everolimus). However, tumour heterogeneity results in an unpredictable response to the therapy, and only a limited number of patients profits from either treatment. To date, no method for diagnostic stratification of patients exists.
A main hypothesis of the project is that improvement of therapy in pNETs can be achieved through a focussed systems biology approach, which considers the patient-individual mutation and expression profile. Patient-individual alterations such as mutations, expression changes and activation states will be represented within a combined MAPK-PI3K-mTOR mathematical model. This model will then be used to predict to what extend therapeutic interferences within these pathways are successful, or whether escape mechanisms are to be expected. We expect a deeper insight into the mechanisms that drive pNETs and furthermore the extraction of potential predictive biomarkers for individualised therapy that can be used in routine diagnostics.