One focus is the elucidation of genetic heterogeneity within tumor cell populations. The genetic pattern represents a "snapshot" of the clonal or subclonal composition of a tumor, and through appropriate longitudinal analyses we use this to track and model tumor evolution. Since this often leads to the outgrowth of individual tumor cell clones in dependence on therapeutic measures, we use this to develop hypotheses on mechanisms that can lead to therapy resistance. We are testing these in preclinical models in vitro and in vivo, including the use of patient-derived cell systems. Ultimately, these approaches serve to successfully counter therapy resistance.

Tumor heterogeneity interests us on the one hand at the level of neoplastic cells. Besides mechanisms to maintain genome stability, our particular research focuses on factors that regulate metabolic processes in the cell. On the other hand, we are interested in non-malignant cells in the tumor microenvironment, i.e. cells of the stroma and immune system. In addition, we investigate the potential pathogenic role of micro-organisms via extensive microbiome analyses in tumor or tumor-near tissue.

For potential clinical applications, we develop and validate predictive markers and gene signatures based on extensive molecular profiling of tumor cells at the level of genome, methylome, transcriptome, and other classes of molecular and cellular structures. This led to the implementation of an active workflow for Personalized Oncology based on genomic and transcriptomic data contributing to alternative or new therapy suggestions within regular Molecular Tumor Boards. Within the NCT Molecular Precision Oncology program.