Potential of Molecular Targeted Therapies in Childhood Brain Tumors (BRAF Inhibitors)

Brain tumors are the most common tumors in childhood, secondary only to leukemia as the most frequent malignancies in that age group. Large multicenter treatment protocols have resulted in cures higher than 80% in acute lymphoblastic leukemia and other hematological malignancies. Unfortunately, in the treatment of pediatric brain tumors the success lags behind. Molecular markers to predict treatment response already at diagnosis have been successfully implemented to determine appropriate treatment intensity for the individual patient with leukemia. Thus, molecular information helps to identify patients with aggressive leukemias for whom maximal therapy is appropriate and others who might survive with less toxic adjuvant therapy. Reduced treatment intensity for low-risk patients minimizes therapy-associated side effects and secondary malignancies. Nowadays, CNS tumors are the single most common cause of cancer-related mortality in childhood. Hence, from a clinical perspective there is an urgent need to identify reliable prognostic markers for childhood brain tumors. To detect prognostic markers in a variety of pediatric CNS tumors (e.g. medulloblastoma, low-grade astrocytoma, ependymoma), we use genome-wide microarray-based screening methods and correlate the results with clinical data. In addition, we aim to elucidate novel pathways in tumorigenesis which might serve as a basis for targeted treatment approaches in the future.