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Sci Rep. 2017 Sep 12;7(1):11410. doi: 10.1038/s41598-017-11764-2.

A multiplex preclinical model for adenoid cystic carcinoma of the salivary gland identifies regorafenib as a potential therapeutic drug.

Author information

1
Department of Pathology, Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, 20007, USA.
2
Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.
3
Department of Pathology, University of Virginia, Charlottesville, VA, 22903, USA.
4
START, San Antonio, TX, 78229, USA.
5
Department of Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC, 20007, USA.
6
Department of Pathology, Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, 20007, USA. sa1137@georgetown.edu.

Abstract

Adenoid cystic carcinomas (ACC) are rare salivary gland cancers with a high incidence of metastases. In order to study this tumor type, a reliable model system exhibiting the molecular features of this tumor is critical, but none exists, thereby inhibiting in-vitro studies and the analysis of metastatic behavior. To address this deficiency, we have coupled an efficient method to establish tumor cell cultures, conditional reprogramming (CR), with a rapid, reproducible and robust in-vivo zebrafish model. We have established cell cultures from two individual ACC PDX tumors that maintain the characteristic MYB translocation. Additional mutations found in one ACC culture also seen in the PDX tumor. Finally, the CR/zebrafish model mirrors the PDX mouse model and identifies regorafenib as a potential therapeutic drug to treat this cancer type that mimic the drug sensitivity profile in PDX model, further confirming the unique advantages of multiplex system.

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