Next generation zebrafish-based drug discovery and precision medicine

Abstract

Even after entering the era of genomic drug discovery in the 21st century, development of a breakthrough therapeutic drug (first-in-class) for intractable diseases (unmet medical needs) has been extremely difficult, but to the US FDA 62% of the approved first-in-class drugs are found by phenotypic screening. The next-generation zebrafish drug discovery enables high-throughput quantitative live in vivo phenotypic screening, and has been impacting global drug discovery strategies now. Compared to severe immunodeficient mice, zebrafish is expected to become a true individualized medical tool as a clinical ex vivo diagnostic system because of the high efficiency and speed of engraftment of patient-derived cancer xenotransplantation. Phenomics-based personalized medicine with the patient-derived cancer xenograft zebrafish in addition to conventional omics platform of individualized medicine is a true next-generation precision medicine to utilize for selection of therapeutic drugs and decision of their doses for the patient, and emerging paradigm shift is realizing in this century.