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Cancer genetics and drug discovery in the zebrafish

Nature Reviews Cancer volume 3, pages 533–539 (2003)Cite this article

Abstract

Fish have a long history of use in cancer toxicology studies, because they develop neoplasms that are histologically similar to human cancers. Because of considerable progress in zebrafish genetics and genomics over the past few years, the zebrafish system has provided many useful tools for studying basic biological processes. These tools include forward genetic screens, transgenic models, specific gene disruptions and small-molecule screens. By combining carcinogenesis assays, genetic analyses and small-molecule screening techniques, the zebrafish is emerging as a powerful system for identifying novel cancer genes and for cancer drug discovery.

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Figure 1: Attributes of the zebrafish system that will impact on the study of cancer biology.
Figure 2: Adenocarcinoma of the pancreas in zebrafish and humans.
Figure 3: Examples of embryonic assays that probe cancer pathways in the zebrafish.
Figure 4: Schematic of a small-molecule screen.

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Acknowledgements

We would like to thank J. Amatruda, C. Belair, C. Erter, K. Lindahl, R. Murphey, E. Patton and J. Shepard for critical reading of the manuscript, and E. Patton for artistic contributions to the figures. K. Cheng, J. Glickman, R. Lamason and J. Moore are thanked for contributing photographs. H.M.S. is supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. L.I.Z. is supported by funds from the National Insitutes of Health and is an Investigator of the Howard Hughes Medical Institute.

Author information

Authors and Affiliations

  1. Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, 02115, Massachusetts, USA

    Howard M. Stern

  2. Howard Hughes Medical Institute, Children's Hospital of Boston, 300 Longwood Avenue, Enders 761, Boston, 02115, Massachusetts, USA

    Howard M. Stern & Leonard I. Zon

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  1. Howard M. Stern
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  2. Leonard I. Zon
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Related links

Related links

DATABASES

LocusLink

ang1

ang2

fli1

Flk1

hex

kit

Mdm2

men1

Myc

nras

rag1

rag2

ret

scl

tie1

tie2

tp53

FURTHER INFORMATION

The Children's Hospital Zebrafish Genome Initiative

Stanford Zebrafish Genome Project

Tübingen Map of the Zebrafish Genome

Washington University Zebrafish Genome Resources Project

Web site for Christine Nüsslein-Volard, Max Plank Institute

Website for Igor Dawid, NICHD

Website for Brant Weinstein, NICHD

The Zebrafish Information Network (ZFIN)

Zebrafish Webserver at the Cardiovascular Research Center, Massachusetts General Hospital

Glossary

DESMOPLASTIC STROMAL RESPONSE

Also called reactive fibrosis. Collagen deposition and fibroblast proliferation as a stromal response to an invasive cancer.

NUCLEAR PLEOMORPHISM

Variation in nuclear size and shape.

PROPTOSIS

An outward protrusion of the eye.

SYNTENY

The arrangement of mapped genes on a single chromosome. All loci on one chromosome are said to be syntenic (literally, 'on the same ribbon').

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Stern, H., Zon, L. Cancer genetics and drug discovery in the zebrafish. Nat Rev Cancer 3, 533–539 (2003). https://doi.org/10.1038/nrc1126

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