Multiscale-Hepatocellular Carcinoma (HCC II)

We will develop models which will predict and mirror tumor development of advanced hepatocellular carcinoma (HCC) under anti-angiogenic therapies, specifically Sorafenib and after transarterial chemoembolisation (TACE). Using our existing base of multifunctional imaging data and pre-existing simulation framework we will reveal functional factors of anti-angiogenic drugs and TACE treatments on the vascular system and tumor cells. Model-based predictions will be correlated with clinical data from the same patient which subsequently validates and refines our models.

The validated and improved mathematical model will then be applied to analyse and optimize different administration schedules for combination therapies.Existing data will be supplemented by multiparametric imaging, metabolomics,transcriptomics, genomics, pathology and clinical data of genetically engineered mouse models as well as by an observational clinical study in HCC patients. Volume perfusion CT and combined PET/MR will reveal complementary functional-molecular parameters of the disease and treatment effects, leading to an image fingerprint of investigated tumors. Network models on the molecular scale will be coupled to spatially resolved tissue models, resulting in a multi-scale description of HCC. These models will be developed, calibrated, and validated against imaging data and omics data, expanding the usual scope of systems biology. Predictions made by the model will be validated in mouse models.

Non-invasive clinical imaging will thus be directly coupled to molecular mechanistic data and answer the question, which type of data will be most effective for selecting optimal therapies.
The consortium is an interdisciplinary group of the Universities Tübingen and Stuttgart and our SME Definiens, covering all required areas of clinical disciplines, advanced mouse models, multimodal imaging, image analysis, data mining, omics data analysis, modeling and bioinformatics.

Project Coordination:
Prof. Dr. rer. nat. Bernd Jürgen Pichler (Project coordinatior)
Clinic of Radiology – University Hospital, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen

1. Prof. Dr. Marius Horger, University of Tübingen, Dept of Diagnostic Radiology,
   72076 Tübingen
2. Prof. Dr. Lars Zender,University of Tübingen, Dept of Internal Medicine I, 72076 Tübingen
3. Prof. Dr. Dr. Matthias Reuss, Stuttgart Research Center Systems Biology (SRCSB), University of Stuttgart, 70569 Stuttgart
   Dr. Alexey Lapin, Stuttgart Research Center Systems Biology (SRCSB), University of Stuttgart
4. Dr. Dieter Hahn, Chimaera GmbH, Erlangen
5. Prof. Dr. Nisar Malek, University of Tübingen, Department of Internal Medicine I, 72076 Tübingen
6. Prof. Dr. Bernd Pichler, University of Tübingen, Dept of Preclinical Imaging and Radiopharmacy, 72076 Tübingen