The multikinase inhibitor RXDX-105 is effective against neuroblastoma in vitro and in vivo

Sean M. Flynn, Jacqueline Lesperance, Andrew Macias, Nikki Phanhthilath, Megan Rose Paul, Jong Wook Kim, Pablo Tamayo, Peter E. Zage

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Neuroblastoma is the most common extracranial solid tumor of childhood and accounts for 15% of all pediatric cancer-related deaths. New therapies are needed to improve outcomes for children with high-risk and relapsed tumors. Inhibitors of the RET kinase and the RAS-MAPK pathway have previously been shown to be effective against neuroblastoma, suggesting that combined inhibition may have increased efficacy. RXDX-105 is a small molecule inhibitor of multiple kinases, including the RET and BRAF kinases. We found that treatment of neuroblastoma cells with RXDX-105 resulted in a significant decrease in cell viability and proliferation in vitro and in tumor growth and tumor vascularity in vivo. Treatment with RXDX-105 inhibited RET phosphorylation and phosphorylation of the MEK and ERK kinases in neuroblastoma cells and xenograft tumors, and RXDX-105 treatment induced both apoptosis and cell cycle arrest. RXDX-105 also showed enhanced efficacy in combination with 13-cis-retinoic acid, which is currently a component of maintenance therapy for children with high-risk neuroblastoma. Our results demonstrate that RXDX-105 shows promise as a novel therapeutic agent for children with high-risk and relapsed neuroblastoma.

Original languageEnglish (US)
Pages (from-to)6323-6333
Number of pages11
Issue number59
StatePublished - 2019


  • BRAF
  • CEP-32496
  • Neuroblastoma
  • RET
  • RXDX-105

ASJC Scopus subject areas

  • Oncology


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