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

Chen Chen; Sujata Choudhury; Darawalee Wangsa; Chamille J. Lescott; Devan J. Wilkins; Praathibha Sripadhan; Xuefeng Liu; Danny Wangsa; Thomas Ried; Christopher Moskaluk; Michael J. Wick; Eric Glasgow; Richard Schlegel; Seema Agarwal

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

Chen Chen, Sujata Choudhury, Darawalee Wangsa, Chamille J. Lescott, Devan J. Wilkins, Praathibha Sripadhan, Xuefeng Liu, Danny Wangsa, Thomas Ried, Christopher Moskaluk, Michael J. Wick, Eric Glasgow, Richard Schlegel, Seema Agarwal^*

^*Corresponding author for this work

McCormick Office of Undergraduate Engineering

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

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.

Original language	English (US)
Article number	11410
Journal	Scientific reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-11764-2
State	Published - Dec 1 2017

Funding

This work was supported by grants (GR409881, GR410902 and GR411273) from Adenoid Cystic Carcinoma Foundation to Dr. Agarwal. This work was also supported in part by internal funding from the Center for Cell Reprogramming at Georgetown University. Facility support was provided by the Animal Models Shared Resource and the Lombardi Comprehensive Cancer Center Microscopy & Imaging Shared Resource at Georgetown University under a grant from U.S. Public Health Service Grants 2P30-CA-51008. The development of the ACC xenograft models was supported by a grant from the National Institute of Dental and Craniofacial Research (NIDCR) #RC1-DE020687, and by grants from the National Organization of Rare Disorders and the Adenoid Cystic Carcinoma Research Foundation to Dr. Moskaluk. Authors also would like to thank Dr. Dieter Zopf from Bayer Pharmaceuticals for kindly providing clinical grade regorafenib to Dr. Wick for xenograft studies. Drs. Xuefeng Liu and Richard Schlegel co-invented the CR technology, which Georgetown University has patented and licensed to Propagenix. Currently there are no annual royalty streams.

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10.1038/s41598-017-11764-2

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Chen, C., Choudhury, S., Wangsa, D., Lescott, C. J., Wilkins, D. J., Sripadhan, P., Liu, X., Wangsa, D., Ried, T., Moskaluk, C., Wick, M. J., Glasgow, E., Schlegel, R., & Agarwal, S. (2017). A multiplex preclinical model for adenoid cystic carcinoma of the salivary gland identifies regorafenib as a potential therapeutic drug. Scientific reports, 7(1), Article 11410. https://doi.org/10.1038/s41598-017-11764-2

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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.",

author = "Chen Chen and Sujata Choudhury and Darawalee Wangsa and Lescott, {Chamille J.} and Wilkins, {Devan J.} and Praathibha Sripadhan and Xuefeng Liu and Danny Wangsa and Thomas Ried and Christopher Moskaluk and Wick, {Michael J.} and Eric Glasgow and Richard Schlegel and Seema Agarwal",

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Chen, C, Choudhury, S, Wangsa, D, Lescott, CJ, Wilkins, DJ, Sripadhan, P, Liu, X, Wangsa, D, Ried, T, Moskaluk, C, Wick, MJ, Glasgow, E, Schlegel, R & Agarwal, S 2017, 'A multiplex preclinical model for adenoid cystic carcinoma of the salivary gland identifies regorafenib as a potential therapeutic drug', Scientific reports, vol. 7, no. 1, 11410. https://doi.org/10.1038/s41598-017-11764-2

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AU - Chen, Chen

AU - Choudhury, Sujata

AU - Wangsa, Darawalee

AU - Lescott, Chamille J.

AU - Wilkins, Devan J.

AU - Sripadhan, Praathibha

AU - Liu, Xuefeng

AU - Wangsa, Danny

AU - Ried, Thomas

AU - Moskaluk, Christopher

AU - Wick, Michael J.

AU - Glasgow, Eric

AU - Schlegel, Richard

AU - Agarwal, Seema

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N2 - 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.

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

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