title: Identifying Novel Cancer Therapies Using Chemical Genetics and Zebrafish.
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.
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, 02115, USA.|Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, 1 Blackfan Circle, Boston, MA, 02115, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Dang
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, 02115, USA.|Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, 1 Blackfan Circle, Boston, MA, 02115, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Fogley
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, 02115, USA. zon@enders.tch.harvard.edu.|Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, 1 Blackfan Circle, Boston, MA, 02115, USA. zon@enders.tch.harvard.edu.
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Zon
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015027:Zebrafish
keywords: Cancer; Chemical genetics; Chemical screen; Drug discovery; Therapeutics; Zebrafish