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

ABSTRACT: 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.

SUBMITTER: Flynn SM

PROVIDER: S-EPMC6824878 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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The multikinase inhibitor RXDX-105 is effective against neuroblastoma <i>in vitro</i> and <i>in vivo</i>.

Flynn Sean M SM Lesperance Jacqueline J Macias Andrew A Phanhthilath Nikki N Paul Megan Rose MR Kim Jong Wook JW Tamayo Pablo P Zage Peter E PE

Oncotarget 20191029 59

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 ki ...[more]

PMID: 31695841

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Dataset Information

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

Publications

The multikinase inhibitor RXDX-105 is effective against neuroblastoma <i>in vitro</i> and <i>in vivo</i>.

Similar Datasets

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