Identifying Novel Cancer Therapies Using Chemical Genetics and Zebrafish

Michelle Dang, Rachel Fogley, Leonard I Zon
Advances in Experimental Medicine and Biology 2016, 916: 103-24
Chemical genetics is the use of small molecules to perturb biological pathways. This technique is a powerful tool for implicating genes and pathways in developmental programs and disease, and simultaneously provides a platform for the discovery of novel therapeutics. The zebrafish is an advantageous model for in vivo high-throughput small molecule screening due to translational appeal, high fecundity, and a unique set of developmental characteristics that support genetic manipulation, chemical treatment, and phenotype detection. Chemical genetic screens in zebrafish can identify hit compounds that target oncogenic processes-including cancer initiation and maintenance, metastasis, and angiogenesis-and may serve as cancer therapies. Notably, by combining drug discovery and animal testing, in vivo screening of small molecules in zebrafish has enabled rapid translation of hit anti-cancer compounds to the clinic, especially through the repurposing of FDA-approved drugs. Future technological advancements in automation and high-powered imaging, as well as the development and characterization of new mutant and transgenic lines, will expand the scope of chemical genetics in zebrafish.

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