Klin Padiatr 2013; 225 - A12
DOI: 10.1055/s-0033-1353463

Personalized pediatric oncology: Targeted Therapy and clinical feasibility

A Deiss 1, A Korshunov 2, 3, H Witt 4, 5, C van Tilburg 4, A von Deimling 2, 3, AE Kulozik 4, S Pfister 3, 4, O Witt 1, 4, T Milde 1, 4
  • 1Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center, Heidelberg, Germany
  • 2Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany
  • 3Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center, Heidelberg, Germany
  • 4Section of Pediatric Brain Tumors, Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany
  • 5Division of Pediatric Neurooncology (B062), German Cancer Research Center, Heidelberg, Germany

Targeted therapy using novel substances such as small molecules and monoclonal antibodies is a promising and probably less toxic therapy compared with conventional chemotherapy. The “Pediatric Targeted Therapy” (PTT) program identifies presence and activity of druggable structures in relapsed tumors on an individual basis for targeted therapies. The PTT-program aims at the evaluation of the feasibility and of the clinical benefit of a personalized medical treatment approach.

To this aim, we analyzed 13 molecular targets indicative of a possible specific inhibition in experimental treatment settings (HDAC 2, 5, 8 and 9, p-AKT, p-ERK, p-S6, p-EGFR, PDGFR-alpha/beta, p53, Integrin avb5 and BRAFV600E), as well as 12 markers suitable for therapeutic and/or risk stratification (HR23B, beta-catenin, SFR1, NPR3, KCNA1, LAMA2, NELL2, nestin, tenascin C, FOXG1, OLIG2, LIN28). Pediatric tumors independent of the histological diagnosis from 35 pediatric oncology centers were included. All Patients had been treated with at least one standard protocol treatment and had experienced relapse or progression of disease. Only formalin fixed paraffin embedded (FFPE)-material was used. Based on the resulting immunohistochemical information a suggestion for treatment in an experimental setting was deduced.

Turnover time from submission to final report was 5,0 weeks. The most common entities were brain tumors (24,4% ependymoma, 16,3% high-grade glioma, 12,8% medulloblastoma), sarcomas (4,7% ewing sarcoma, 2,3% osteosarcoma, 3,5% desmoid tumors) and neuroblastoma (3,5%).

The most commonly expressed or activated pathways were HDACs (81/84, 96,4%), pEGFR (39/52; 75,0%) and PDGFR (46/66; 69,7%). A suggestion for treatment was given in 83/86 (96,5%) cases with adequate tissue available. Finally, 71 of 86 tested tumors analyzed displayed more than one targetable alteration, implying the need for a combination strategy employing several targeted therapies. Promising responses in individual cases warrant further systematic studies of this approach.