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2018/02/24

Zebrafish-Based Drug Discovery and Precision Pharmacology

We will report 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 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 precision 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 patient-derived 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.
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.

Joint Meeting of JSCB 70th & JSDB 51st