Background: Pediatric neurogenic tumors are the second most frequent cause of death of children under the age of 15. Many high-risk solid tumors still show only poor therapy responses and current therapeutic approaches are suboptimal for some children. Both RTKs and downstream kinases are part of signaling pathways that determine cell movement, proliferation, differentiation or apoptosis and they coordinate and precisely integrate all important decisions within the cell[1.Ren H. Yang B.F. Rainov N.G. Receptor tyrosine kinases as therapeutic targets in malignant glioma.E: Recent Clin. Trials. 2007; 2: 87-101Crossref PubMed Scopus (25) Google Scholar]. Furthermore, it has been shown that as many as 30% of the RTKs are repeatedly found mutated or overexpressed in different malignancies[2.Blume-Jensen P. Hunter T. Oncogenic kinase signalling.Nature. 2001; 411: 355-365Crossref PubMed Scopus (3136) Google Scholar]. Therefore, our study focuses on the revelation of the activity of RTKs and downstream signaling molecules in pediatric neurogenic tumors and it is expected to bring completely new information about how the changes in RTKs and downstream kinases phosphorylation influence the character of pediatric neurogenic tumors. Methods: The determination of the phosphorylation status of 49 different RTKs was performed using the Human Phospho-RTK Array Kit (R&D Systems). The relative levels of phosphorylation of 24 MAPKs, serin/threonin kinases and other downstream signaling molecules was detected by Human Phospho-MAPK Array Kit (R&D Systems). Results: We have analyzed 52 samples of pediatric neurogenic tumors obtained from 40 patients. These samples were categorized according to the International Classification of Childhood Cancer (ICCC-3). This cohort consisted of 12 astrocytomas, followed by 11 ependymomas and choroid plexus tumors, 11 neuroblastomas, 7 samples of other gliomas, 6 medulloblastomas and 5 primitive neuroectodermal tumors (PNET). We revealed significant phosphorylation in both RTKs and downstream kinases. Namely the activities of EGFR, ROR2, InsR, ERK2 or HSP27 are usually high in all of tumor types mentioned above. We have also reported high phosphorylation of TrkA and JNK in neuroblastomas and this difference clearly distinguishes this tumor type from all others. Conclusions: Our results identified specific phosphorylation patterns of the most common childhood neurogenic tumors. These RTKs and downstream signaling molecules may play a role as promising putative targets for a future therapy based on small-molecule inhibitors. This is supposed to lead to more personalized therapeutic approach with better response and it will therefore reduce the amount of harmful side effects and long-term disability. Legal entity responsible for the study Department of Pediatric Oncology, University Hospital Brno and School of Medicine, Masaryk University, Brno, Czech Republic Funding: AZV MZCR 16-34083A Disclosure: All authors have declared no conflicts of interest