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Zebrafish-Based Drug Discovery and Precision Pharmacology

                     

2018/07/01

We introduce the strategy of zebrafish-based quantitative and systems pharmacology, which synergistically combine the desirable features of systems pharmacology and emerging technology of zebrafish-based screening system for functional omics and chemical biology. We have discovered novel fluorescent selective inhibitor of cancer stem cells (Biomaterials 2015, 52:14). Zebrafish-based systems pharmacology that analyze in vivo regulatory networks involved in drug action can account for a drug's multiple targets and for the effects of genomic, epigenomic, and posttranslational changes on the drug efficacy and toxicology. We found that stanniocalcin 1 gene is responsible for molecular targeted anticancer drug sorafenib-induced cardiotoxicity (Toxicol.Sci. 2015, 143:374) . Zebrafish-based drug discovery has become a potential strategy by its high throughput quantitative in vivo screening and has already succeeded in several examples of phenotype-based drug discovery and personalized medicine (Nat Rev Drug Discov.2015,14:721).
The pancreatic cancer is a solid tumor with high mortality and the therapeutic response is very low with the poor clinical prognosis and omics-based personalized medical treatment aren't achieved.
A quantitative in vivo imaging of zebrafish system was developed originally as a new clinical cancer xenotransplantation model. The therapeutic sensitivity of the clinical pancreatic cancer sample is analyzed within 100 hours and the medical diagnosis which achieve next generation direct phenomics-based individualized medical treatment has been developed in this study.
Clinical cancer xenotransplantation in zebrafish within 36 hours post fertilization with the immature immunity take rate approximately 100 % for pancreatic cancer transplantation in vivo imaging system have been developed in this research. We have made it possible to quantify the ex vivo therapeutic response in 48 hours by xenotransplantation of 100 clinical pancreatic cancer cells in each zebrafish. We have established the validity of the curative susceptibility test of a clinical cancer sample and aim at practical use of medicine for phenomics-based precision medicine for pancreatic cancer.
This new translational pharmacology can drive drug discovery and shape precision medicine.



関連リンク

第１８回国際薬理学・臨床薬理学会議

三重大学大学院医学系研究科システムズ薬理学