ColoNET – A systems biology approach for integrating molecular diagnostics and targeted therapy in colorectal cancer

The major objective of the project is to accomplish an in silico network of genetic, epigenetic and signaling processes to tailor diagnostics with predictive information for therapies targeting receptor tyrosine kinases (e.g. EGFR) in colorectal cancer. The network model is expected to provide diagnostic guidance for the improvement of therapy response prediction by achieving an in-depth functional understanding of receptor-mediated signaling and downstream processes. The core model will consist of a “static” colon-specific signaling network model that serves as a framework for integrating detailed kinetic models of MAPK and Wnt pathways, existing genetic/epigenetic information, high-throughput data, knowledge on predictive markers obtained by literature mining, and physiologically relevant data. The dynamics of MAPK and Wnt pathways, which are crucial for targeted therapies, will be subjected to detailed mathematical modeling based on results from focused experimental measurements. Once detailed models of pathways, key signaling nodes, feed-back loops and marker combinations are established, we will turn the static network into a dynamic model in an iterative process. Finally, this approach should generate a tool for the in silico evaluation of novel markers or combinations of them for an improved therapy prediction. We expect that our models will also be useful for other types of cancer and related predictive diagnostics.

 

Partners

Christine Sers, Charité; Coordiator

Hanspeter Herzel, HU/Charité; Coordinator

Nils Blüthgen, Charité

Reinhold Schäfer, Charité

Manfred Dietel, Charité

Peter-Michael Schlag, Charité

Ulf Leser, HU

Edda Klipp, HU

Joachim Selbig, University Potsdam

Christoph Röcken, University Kiel,

Jörn Walter, University Saarland

Barbara Seliger, University Halle

Holger Sültmann, DKFZ

Microdiscovery, Berlin

Iduna Fichtner EPO, MDC

 

Supported by: BMBF, MedSYS

05/2009 – 12/2012

 

Group leader

Prof. Dr. rer. nat. Christine Sers
Head of group Mol. Tumor Pathology, Head of group Tumor Systems Biology
t: +49 30 450 536 185