{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:33:14Z","timestamp":1792801994944,"version":"4.5.0"},"reference-count":45,"publisher":"The Company of Biologists","issue":"5","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Medical Research Council","award":["MC_UU_00007\/9"],"award-info":[{"award-number":["MC_UU_00007\/9"]}]},{"name":"European Research Council","award":["ZF-MEL-CHEMBIO-648489"],"award-info":[{"award-number":["ZF-MEL-CHEMBIO-648489"]}],"id":[{"id":"https:\/\/ror.org\/0472cxd90","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005190","name":"Melanoma Research Alliance","doi-asserted-by":"crossref","award":["687306"],"award-info":[{"award-number":["687306"]}],"id":[{"id":"10.13039\/100005190","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Zebrafish embryos are widely used for drug discovery, however, administering drugs to adult zebrafish is limited by current protocols that can cause stress. Here, we developed a drug formulation and administration method for adult zebrafish by producing food-based drug pellets that are consumed voluntarily. We applied this to zebrafish with BRAF-mutant melanoma, a model that has significantly advanced our understanding of melanoma progression, but not of drug resistance due to the limitations of current treatment methods. Zebrafish with melanomas responded to short-term, precise and daily dosing with drug pellets made with the BRAFV600E inhibitor, vemurafenib. On-target drug efficacy was determined by phospho-Erk staining. Continued drug treatment led to the emergence, for the first time in zebrafish, of acquired drug resistance and melanoma relapse, modelling the responses seen in melanoma patients. This method presents a controlled, non-invasive approach that permits long-term drug studies and can be widely applied to adult zebrafish models.<\/jats:p>","DOI":"10.1242\/dmm.049401","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T05:46:00Z","timestamp":1649396760000},"source":"Crossref","is-referenced-by-count":24,"title":["Long-term non-invasive drug treatments in adult zebrafish that lead to melanoma drug resistance"],"prefix":"10.1242","volume":"15","author":[{"given":"Yuting","family":"Lu","sequence":"first","affiliation":[{"name":"MRC Human Genetics Unit and CRUK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital Campus, EH4 2XU, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2570-0834","authenticated-orcid":false,"given":"E. Elizabeth","family":"Patton","sequence":"additional","affiliation":[{"name":"MRC Human Genetics Unit and CRUK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital Campus, EH4 2XU, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2022,5,9]]},"reference":[{"key":"2022050908590759200_DMM049401C1","doi-asserted-by":"publisher","first-page":"5185","DOI":"10.1172\/JCI124649","article-title":"Mosaic RAS\/MAPK variants cause sporadic vascular malformations which respond to targeted therapy","volume":"128","author":"Al-Olabi","year":"2018","journal-title":"J. Clin. 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