The Pediatric Brain Tumor Preclinical Testing Program: update and perspectives

The Pediatric Brain Tumor Preclinical Testing Program aims at the evaluation of the clinical benefit and of the feasibility of an individualized treatment approach.

All available pediatric brain tumors independent of the histological diagnosis from cooperating pediatric oncology centers are included. All tumors are subjected to molecular analyis by gene expression profiling, as well as sequencing in individual cases, allowing for identification of activated signaling pathways. Primary tumor material is transplanted orthotopically into mice. Secondary xenografts will be treated according to the results from the molecular analysis. Approved drugs available in pediatric oncology as well as novel therapeutic agents are used, in order to select for translatable therapeutic strategies, as well as open up new treatment possibilities for the future.

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.

Tumormaterial was received from 8 centers in Germany. Relative frequencies reflected incidence of tumor entities in children withlow grade gliomas being the most frequent entity sent (51,1%), followed by medulloblastoma (12,8%), ependymoma (9,6%) and high grade gliomas (7,4%). 62,6% of all collected samples were transplanted, 28.6% of transplanted samples within one day of receipt, 19,0% in 2 – 3 days, 17.5% in 4 – 5 days, and 34.9%after 6 days or more. 5 medulloblastoma-, 2 glioblastoma- and 1 ependymoma-xenograft model were generated. No low grade xenografts were generated to date.

An update on the current status and feasibility of the program, as well as future perspectives are presented.

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