Fibroblast growth factor receptors as therapeutic targets in neuroblastoma

To identify progression-driving molecular alterations in neuroblastoma, we used DNA deep-sequencing of 213 primary tumors, RNA deep-sequencing of 498 primary tumors, and microarray gene expression analysis of 709 tumors. While a heterogeneous mutation spectrum was observed in general, we identified putatively activating mutations in fibroblast growth factor receptor (FGFR) tyrosine kinase genes in several cases of high-risk neuroblastoma patients. In addition, gene expression data suggest that elevated FGFR expression in neuroblastoma is associated with a poor patient outcome, suggesting that FGFR may represent therapeutic targets in neuroblastoma. We are therefore investigating the effects of the FGFR inhibitors Dovitinib (TKI-258) and NVP-BGJ398, which have shown promising anticancer-activity in other malignancies, on growth characteristics of neuroblastoma cell lines. We observed that FGFR are highly expressed in the majority of the analysed neuroblastoma cell lines. Preliminary results of Dovitinib indicate that FGFR kinases may be suitable as a molecular target in neuroblastoma therapy.