Analysis of therapy response in patients and cell lines with specific mutation profiles
The subproject is responsible for the establishment and characterization of pNET-specific cell culture models as well as for generation of data for parameterization of mathematical models. In addition, high-throughput NGS data will be generated from suitable patients that were treated within Charité to determine the most important genetic alterations in these tumors. Furthermore, app. 150 of the most important components of the MAPK-mTOR network will be suppressed using shRNA and the effects onto MAPK and mTOR acitivity will be measured. This will identify the specific connectivity of the MAPK-mTOR network within the tumor cells. For parameterization of the mathematical models, a specific high-throughput approach previously established in other tumor cells will be applied. In parallel, growth, cell cycle analysis and apoptosis will be measured. During the course of the project, predictions derived by use of the mathematical models will be experimentally verified.
Keywords: Modellparameterisierung, PI3K, mTOR, Signalling, pancreatic neuroendicrine tumors (pNET)