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

涎腺腺样囊性癌的多重临床前模型确定瑞戈非尼是一种潜在的治疗药物

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作者: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

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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