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Rapid in vivo validation of HDAC inhibitor-based treatments in neuroblastoma zebrafish xenografts

The survival rate among children with relapsed neuroblastomas continues to be poor, and thus new therapeutic approaches identified by reliable preclinical drug testing models are urgently needed. Zebrafish are a powerful vertebrate model in preclinical cancer research. Here, we describe a zebrafish...

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Main Authors: Wrobel, Jagoda (Author) , Najafi, Sara (Author) , Ayhan, Simay (Author) , Gatzweiler, Charlotte (Author) , Krunic, Damir (Author) , Ridinger, Johannes (Author) , Milde, Till (Author) , Westermann, Frank (Author) , Peterziel, Heike (Author) , Meder, Benjamin (Author) , Distel, Martin (Author) , Witt, Olaf (Author) , Oehme, Ina (Author)
Format: Article (Journal)
Language:English
Published: 27 October 2020
In: Pharmaceuticals
Year: 2020, Volume: 13, Issue: 11
ISSN:1424-8247
DOI:10.3390/ph13110345
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/ph13110345
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/1424-8247/13/11/345
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Author Notes:Jagoda K. Wrobel, Sara Najafi, Simay Ayhan, Charlotte Gatzweiler, Damir Krunic, Johannes Ridinger, Till Milde, Frank Westermann, Heike Peterziel, Benjamin Meder, Martin Distel, Olaf Witt and Ina Oehme

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520 |a The survival rate among children with relapsed neuroblastomas continues to be poor, and thus new therapeutic approaches identified by reliable preclinical drug testing models are urgently needed. Zebrafish are a powerful vertebrate model in preclinical cancer research. Here, we describe a zebrafish neuroblastoma yolk sac model to evaluate efficacy and toxicity of histone deacetylase (HDAC) inhibitor treatments. Larvae were engrafted with fluorescently labeled, genetically diverse, established cell lines and short-term cultures of patient-derived primary cells. Engrafted tumors progressed locally and disseminated remotely in an intact environment. Combination treatments involving the standard chemotherapy doxorubicin and HDAC inhibitors substantially reduced tumor volume, induced tumor cell death, and inhibited tumor cell dissemination to the tail region. Hence, this model allows for fast, cost-efficient, and reliable in vivo evaluation of toxicity and response of the primary and metastatic tumor sites to drug combinations. 
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