PUBLICATION

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

Authors
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.
ID
ZDB-PUB-170914-2
Date
2017
Source
Scientific Reports   7: 11410 (Journal)
Registered Authors
Glasgow, Eric
Keywords
Cancer, Oncology
MeSH Terms
  • Gene Expression Regulation, Neoplastic
  • Zebrafish
  • Salivary Gland Neoplasms/drug therapy*
  • Salivary Gland Neoplasms/genetics
  • Salivary Gland Neoplasms/pathology
  • Biomarkers, Tumor
  • In Situ Hybridization, Fluorescence
  • Humans
  • Mice
  • Pyridines/pharmacology*
  • Carcinoma, Adenoid Cystic/drug therapy*
  • Carcinoma, Adenoid Cystic/genetics
  • Carcinoma, Adenoid Cystic/pathology
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Animals
  • Antineoplastic Agents/pharmacology*
  • Microsatellite Repeats
  • Cell Transformation, Neoplastic/genetics
  • Cell Transformation, Neoplastic/metabolism
  • Phenylurea Compounds/pharmacology*
  • Xenograft Model Antitumor Assays
  • Cell Line, Tumor
  • Gene Expression Profiling
  • Oncogene Proteins, Fusion/genetics
  • Oncogene Proteins, Fusion/metabolism
PubMed
28900283 Full text @ Sci. Rep.
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping