Prof. Dr. med. Olaf Witt

HDAC-inhibitors induce differentiation in neuroblastoma cells

The goal of the CCU Pediatric Oncology is to advance the therapy for children and adolescence with neural cancers. Since epigenetic regulation of gene expression is a key mechanism in stem cell biology, differentiation and development, it is likely that aberrant epigenetic programs play a particular role in the genesis and progression of undifferentiated pediatric cancers. Epigenetic programs are reversibly controlled by a machinery of enzymes including the family of histone deacetylases (HDACs). Understanding the molecular biology and selective targeting of individual HDACs of pediatric neural cancer cells including cancer stem cells is one of the central molecular concepts of the CCU Pediatric Oncology. We have identified particular HDAC family members controlling differentiation, cell survival mechanisms, developmental pathways and self renewal in neuroblastoma and brain tumors. As a consequence, we are now developing small molecule compounds specifically inhibiting distinct HDACs for therapeutic purposes in collaboration with pharma partners. A second research focus concerns the development of individualized, molecular based targeted treatment concept from patient to bench and back. Finally, we translate our experimental findings into clinical practice through development of individual targeted treatment protocols for children and adolescents with relapsed cancers as well as conducting phase I-III clinical trials in pediatric oncology based on rational molecular concepts.