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01.09.2016 | PRECLINICAL STUDIES | Ausgabe 6/2016

Investigational New Drugs 6/2016

The novel kinase inhibitor ponatinib is an effective anti-angiogenic agent against neuroblastoma

Zeitschrift:
Investigational New Drugs > Ausgabe 6/2016
Autoren:
Sarah B. Whittle, Kalyani Patel, Linna Zhang, Sarah E. Woodfield, Michael Du, Valeria Smith, Peter E. Zage
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The online version of this article (doi:10.​1007/​s10637-016-0387-y) contains supplementary material, which is available to authorized users.

Summary

Background High-risk neuroblastoma has poor outcomes with high rates of relapse despite aggressive treatment, and novel therapies are needed to improve these outcomes. Ponatinib is a multi-tyrosine kinase inhibitor that targets many pathways implicated in neuroblastoma pathogenesis. We hypothesized that ponatinib would be effective against neuroblastoma in preclinical models. Methods We evaluated the effects of ponatinib on survival and migration of human neuroblastoma cells in vitro. Using orthotopic xenograft mouse models of human neuroblastoma, we analyzed tumors treated with ponatinib for growth, gross and histologic appearance, and vascularity. Results Ponatinib treatment of neuroblastoma cells resulted in decreased cell viability and migration in vitro. In mice with orthotopic xenograft neuroblastoma tumors, treatment with ponatinib resulted in decreased growth and vascularity. Conclusions Ponatinib reduces neuroblastoma cell viability in vitro and reduces tumor growth and vascularity in vivo. The antitumor effects of ponatinib suggest its potential as a novel therapeutic agent for neuroblastoma, and further preclinical testing is warranted.

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