MAPTor-NET: MAPK-mTOR network model driven individualized therapies of pancreatic neuro-endocrine tumors (pNETs)

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Project description

Pancreatic NET (pNET) comprise the most prominent subgroup group of rare neuroendocrine tumors (NET) with distinct prognostic classes, and thus diverse therapeutic regimens. Available pNET treatments include somatostatin analogs, systemic chemotherapy, and novel molecular drugs targeting receptor tyrosine kinases (Sunitinib), or the mTOR pathway (Everolimus). However, tumor 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 indivualised therapy that can be used in routine diagnostics.

The following image represents the global copy number aberration of a highly proliferative metastasis of Pancreatic Neuroendocrine tumors (PNETs):

The data was obtained from Infinium MethylationEPIC BeadChip of Illumina. The analysis was done by Dr. David Capper (German Cancer Consortium (DKTK), Partner site Berlin and Charite University of Medicine, Institute of Neuropathology, Berlin).

ABL Inhibition leads to Morphological Change in BON-1


Consortium

Coordinator:

Prof. Dr. Christine Sers
Institute of Pathology (CharitéUniversitätsmedizin Berlin)

Co-Investigators:

  1. Prof. Dr. Kathrin Thedieck
    Institut für Biologie und Umweltwissenschaften, Neurogenetik
    Carl von Ossietzky Universität Oldenburg, D
    University Medical Center Groningen, Center for Liver, Digestive and Metabolic Diseases and Systems Biology Centre for Metabolism and Ageing, University of Groningen, NL
  2. Prof. Dr. Nils Blüthgen
    Institute of Pathology, Systems Biology of Molecular Networks
    Charité, University Medicine Berlin
  3. Prof. Dr. med. Marianne Pavel
    Medizinische Klinik m. S. Hepatologie und Gastroenterologie
    Charité, University Medicine Berlin
    Now:
    Universitätsklinikum Erlangen
    Leiterin Schwerpunkt Endokrinologie und Diabetologie
  4. Dr. Katharina Detjen
    Medizinische Klinik m. S. Hepatologie und Gastroenterologie
    Charité, University Medicine Berlin
  5. Prof. Dr. Ulf Leser
    Institute for Computer Science
    Humboldt-Universität zu Berlin

Further Information about the MAPTor-NET project.