Editing Zebrafish (section)

===Cancer===
Zebrafish have been used to make several transgenic models of cancer, including [[melanoma]], [[leukemia]], [[pancreatic cancer]] and [[hepatocellular carcinoma]].<ref>{{cite journal |vauthors=Liu S, Leach SD |title=Zebrafish models for cancer |journal=[[Annual Review of Pathology]] |volume=6 |pages=71–93 |year=2011 |pmid=21261518 |doi=10.1146/annurev-pathol-011110-130330}}</ref><ref>{{cite web |url=https://www.sciencedaily.com/releases/2011/03/110323141852.htm |title=Zebrafish model of human melanoma reveals new cancer gene |website=[[Science Daily]] |date=March 23, 2011 |access-date=April 28, 2014 |archive-date=May 19, 2024 |archive-url=https://web.archive.org/web/20240519141132/https://www.sciencedaily.com/releases/2011/03/110323141852.htm |url-status=live}}</ref> Zebrafish expressing mutated forms of either the BRAF or NRAS [[oncogene]]s develop melanoma when placed onto a p53 deficient background. [[Histology|Histologically]], these tumors strongly resemble the human disease, are fully transplantable, and exhibit large-scale genomic alterations. The BRAF melanoma model was utilized as a platform for two screens published in March 2011 in the journal ''Nature''. In one study, the model was used as a tool to understand the functional importance of genes known to be amplified and overexpressed in human melanoma.<ref>{{cite journal |vauthors=Ceol CJ, Houvras Y, Jane-Valbuena J, Bilodeau S, Orlando DA, Battisti V, Fritsch L, Lin WM, Hollmann TJ, Ferré F, Bourque C, Burke CJ, Turner L, Uong A, Johnson LA, Beroukhim R, Mermel CH, Loda M, Ait-Si-Ali S, Garraway LA, Young RA, Zon LI |display-authors=6 |title=The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset |journal=[[Nature (journal)|Nature]] |volume=471 |issue=7339 |pages=513–517 |date=March 2011 |pmid=21430779 |pmc=3348545 |doi=10.1038/nature09806 |bibcode=2011Natur.471..513C}}</ref> One gene, SETDB1, markedly accelerated tumor formation in the zebrafish system, demonstrating its importance as a new melanoma oncogene. This was particularly significant because SETDB1 is known to be involved in the epigenetic regulation that is increasingly appreciated to be central to tumor cell biology.

In another study, an effort was made to therapeutically target the genetic program present in the tumor's origin [[neural crest]] cell using a chemical screening approach.<ref>{{cite journal |vauthors=White RM, Cech J, Ratanasirintrawoot S, Lin CY, Rahl PB, Burke CJ, Langdon E, Tomlinson ML, Mosher J, Kaufman C, Chen F, Long HK, Kramer M, Datta S, Neuberg D, Granter S, Young RA, Morrison S, Wheeler GN, Zon LI |display-authors=6 |title=DHODH modulates transcriptional elongation in the neural crest and melanoma |journal=[[Nature (journal)|Nature]] |volume=471 |issue=7339 |pages=518–522 |date=March 2011 |pmid=21430780 |pmc=3759979 |doi=10.1038/nature09882 |bibcode=2011Natur.471..518W}}</ref> This revealed that an inhibition of the DHODH protein (by a small molecule called leflunomide) prevented development of the neural crest stem cells which ultimately give rise to melanoma via interference with the process of [[transcriptional elongation]]. Because this approach would aim to target the "identity" of the melanoma cell rather than a single genetic mutation, leflunomide may have utility in treating human melanoma.<ref>{{cite news |url=https://www.sciencedaily.com/releases/2011/03/110323141838.htm |title=Arthritis Drug Could Help Beat Melanoma Skin Cancer, Study Finds |newspaper=Sciencedaily |date=March 24, 2011 |access-date=November 15, 2012 |archive-date=May 19, 2024 |archive-url=https://web.archive.org/web/20240519141108/https://www.sciencedaily.com/releases/2011/03/110323141838.htm |url-status=live}}</ref>