Small molecule inhibitor regorafenib inhibits RET signaling in neuroblastoma cells and effectively suppresses tumor growth in vivo.

摘要: Neuroblastoma (NB), the most common extracranial pediatric solid tumor, continues to cause significant cancer-related morbidity and mortality in children. Dysregulation of oncogenic receptor tyrosine kinases (RTKs) has been shown contribute tumorigenesis various human cancers targeting these RTKs had therapeutic benefit. RET is an RTK which commonly expressed NB, high expression correlates with poor outcomes patients NB. Herein we report that required for NB cell proliferation small molecule inhibitor regorafenib (BAY 73-4506) blocks glial derived neurotrophic factor (GDNF)-induced signaling cells inhibits growth both vitro vivo. We found significantly inhibited colony formation ability cells. Moreover, suppressed tumor orthotopic xenograft mouse model a TH-MYCN transgenic model. Finally, markedly improved overall survival tumor-bearing mice. In summary, our study suggests potential target using novel inhibitor, like regorafenib, should be investigated as treatment option children