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- W3029014793 abstract "Abstract Background Regorafenib is an inhibitor of multiple kinases with aberrant expression and activity in neuroblastoma tumours that have potential roles in neuroblastoma pathogenesis. Methods We evaluated neuroblastoma cells treated with regorafenib for cell viability and confluence, and analysed treated cells for apoptosis and cell cycle progression. We evaluated the efficacy of regorafenib in vivo using an orthotopic xenograft model. We evaluated regorafenib-mediated inhibition of kinase targets and performed reverse-phase protein array (RPPA) analysis of neuroblastoma cells treated with regorafenib. Lastly, we evaluated the efficacy and effects of the combination of regorafenib and 13- cis -retinoic acid on intracellular signalling. Results Regorafenib treatment resulted in reduced neuroblastoma cell viability and confluence, with both induction of apoptosis and of cell cycle arrest. Regorafenib treatment inhibits known receptor tyrosine kinase targets RET and PDGFRβ and intracellular signalling through the RAS/MAPK, PI3K/Akt/mTOR and Fos/Jun pathways. Regorafenib is effective against neuroblastoma tumours in vivo, and the combination of regorafenib and 13- cis -retinoic acid demonstrates enhanced efficacy compared with regorafenib alone. Conclusions The effects of regorafenib on multiple intracellular signalling pathways and the potential additional efficacy when combined with 13- cis -retinoic acid represent opportunities to develop treatment regimens incorporating regorafenib for children with neuroblastoma." @default.
- W3029014793 created "2020-06-05" @default.
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- W3029014793 date "2020-05-27" @default.
- W3029014793 modified "2023-10-14" @default.
- W3029014793 title "Regorafenib is effective against neuroblastoma in vitro and in vivo and inhibits the RAS/MAPK, PI3K/Akt/mTOR and Fos/Jun pathways" @default.
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- W3029014793 doi "https://doi.org/10.1038/s41416-020-0905-8" @default.
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