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Identifying Novel Cancer Therapies Using Chemical Genetics and Zebrafish

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Cancer and Zebrafish

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 916))

Abstract

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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Acknowledgements

The authors thank Christian Lawrence and Kara Maloney for their input on zebrafish spawning technologies and zebrafish husbandry. The authors also thank Justin L. Tan, Charles K. Kauffman, and Owen J. Tamplin for their expertise on chemical genetics in the zebrafish. Leonard I. Zon is an investigator of the Howard Hughes Medical Institute. Leonard I. Zon is a founder and stockholder of Fate, Inc.

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Authors and Affiliations

  1. Stem Cell Program and Division of Hematology/Oncology, Boston Children’s Hospital, Boston, MA, 02115, USA

    Michelle Dang, Rachel Fogley & Leonard I. Zon

  2. Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, 1 Blackfan Circle, Boston, MA, 02115, USA

    Michelle Dang, Rachel Fogley & Leonard I. Zon

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  1. Michelle Dang
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  2. Rachel Fogley
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  3. Leonard I. Zon
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Correspondence to Leonard I. Zon .

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Editors and Affiliations

  1. Molecular Pathology and Cancer Center, Massachusetts General Hospital, CHARLESTOWN, Massachusetts, USA

    David M. Langenau

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Dang, M., Fogley, R., Zon, L.I. (2016). Identifying Novel Cancer Therapies Using Chemical Genetics and Zebrafish. In: Langenau, D. (eds) Cancer and Zebrafish. Advances in Experimental Medicine and Biology, vol 916. Springer, Cham. https://doi.org/10.1007/978-3-319-30654-4_5

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