The Pediatric Brain Tumor Preclinical Testing Program: evaluation of an individualized molecular treatment approach

Pediatric brain tumors remain the most challenging diseases in pediatric oncology in terms of mortality. The concept of individualized treatment in cancer is highly promising, although still a vision of the future. The Pediatric Brain Tumor Preclinical Testing Program aims at the evaluation of the clinical benefit and of the feasibility of such an individualized approach.

To this aim, we will include all available pediatric brain tumors independent of the histological diagnosis from seven pediatric oncology centers. All tumors will be subjected to molecular analyis by array-comparative genomic hybridization (aCGH) and gene expression profiling, allowing for identification of activated signaling pathways. For each tumor, differenzially regulated pathways will be identified in a comparative analysis using an existing large database of aCGH and gene expression array data of pediatric brain tumor samples. All pathways will be filtered for clinical availability of drugs targeting the respective pathway. In a second step, promising delineated pathways will be validated by immunohistochemistry (IHC) on matching paraffin-embedded tumor samples. At the same time, primary tumor material will be transplanted orthotopically into mice. In a third step, secondary xenografts will be treated according to the results from the molecular analysis, using approved drugs that are readily available in pediatric oncology. Response in animals will be measured by MRI according to criteria used in the clinical setting (RECIST).

The program aims for providing pre-clinical proof-of-concept of feasibility and efficacy of individualized targeted therapies based on molecular analysis independent of histological diagnosis.

Funding: National Center for Tumor Diseases – Interdisciplinary Research Program (NCT-IFP)