Summary

Mechanisms of therapy resistance and innovative 3D-models of cancer

Our translational research is focussed on primary human cancer tissue. The main research interests of the group are the molecular mechanisms of therapy resistance in malignant tumors, the identification of prognostic and predictive tumor markers, and the development of novel three-dimensional tumor models.
1.) Molecular mechanisms of therapy resistance in malignant tumors:   One of the central topics in modern tumor pathology are the molecular regulation mechanisms of cell death. Defects in the intracellular signaling cascades which normally should result in cell death are responsible for the resistance to chemo-, radio-, and targeted therapy in many types of cancer. Our research is focussed on the molecular mechanisms which allow tumor cells to evade apoptotic or non-apoptotic cell death. The identification of these resistance mechanisms is a prerequisite for the development of novel effective therapy approaches.
2.) Innovative 3D-models of cancer:   Predicting the clinical response to anti-cancer therapy is one of the major challenges in modern oncology. Despite the progress in targeted therapy approaches and comprehensive molecular sequencing techniques, many patients do not benefit from therapy and for numerous agents there are no useful predictive biomarkers to guide patient stratification. Up to now, therapeutic decision-making is based on “static” features of dead tumor tissue (histology, immunohistochemistry, mutation analysis, expression analysis) without the possibility to measure “dynamic” cellular functions or responses to specific (drug-induced) pertubation. Therefore, the group develops novel ex vivo tumor tissue models (such as the tumor tissue slice technique) to obtain reliable and less artificial models for studying tumor biology. Specifically, human tumor tissue models to directly evaluate drug response and resistance are developed. The integration of response patterns with large-scale mutational analysis data will provide a comprehensive phenotype-genotype profile that guides individual therapeutic decisions. Additionally, improved ex vivo tumor models will substantially promote the precise characerization of crucial hallmarks of cancer, such as heterogeneity and resistance.