Assessment of the role of FGFR1(N546K) mutations in neuroblastoma pathogenesis and treatment

Roughly half of the neuroblastoma patients have fatal disease progression despite multimodal treatment. In a small subgroup of high-risk neuroblastoma patients FGFR1N546K mutations were detected. These patients were characterised by chemotherapy resistance and fatal disease progression. Since oncogenic molecular alterations of the receptor tyrosine kinase FGFR exist in multiple solid tumors, the aim of this project is to determine the oncogenic role of FGFR1N546K mutations in neuroblastoma and their potential value as therapeutic target.

For this purpose, I will generate FGFR1N546K  expressing cells to evaluate the in vitro effect of FGFR inhibitors. In addition, I will use a FGFR1N546K transgenic mouse model to validate FGFR1N546K as a driver mutation in neuroblastoma. I will also examine the response of these tumors to chemotherapy and to the FGFR inhibitor erdafitinib, which was recently approved for the treatment of urothelial cancer.

I expect that our study will contribute to assess the potential of FGFR inhibitors as a targeted therapy for FGFR mutation-positive neuroblastoma patients.