We aim at developing novel therapeutic strategies based on new insights into the molecular mechanisms of disease following two major lines of research. Our investigations start with the analysis of the patients’ tumors in situ, followed by studying patient-derived cell lines using a wide variety of in silico, in vitro, and in vivo techniques.
1. Tumorigenesis in the context of developmental pat
hways:
Dominant oncogenes often hijack or interfere with developmental pathways thereby conferring a considerable growth advantage to tumor cells. We are interested in the mechanisms through which oncogenes arrest sarcoma cells in a lineage-specific, early-committed but yet largely undifferentiated state via deregulation of key developmental pathways, and how they cooperate with them to promote tumorigenesis and cancer progression.
2. Therapy resistance, tumor heterogeneity, and predictive biomarkers:
Primary and/or secondary resistance to conventional chemotherapeutic drugs is a frequent event in pediatric sarcoma. Chemo-resistance is a highly specific process in which tumors become resistant to certain drugs while maintaining (limited) susceptibility toward others. Underlying to this resistance is considerable plasticity due to intra-tumor heterogeneity, which enables the adaptation to therapeutic stress on the clonal and sub-clonal level. We strive for illuminating the genetic basis and biological mechanisms of tumor-heterogeneity and aim at identifying novel biomarkers for individualized risk-stratification, prediction of treatment response, and to indicate which targeted therapeutics may help overcoming resistance to conventional therapeutic drugs.
