{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:19:04Z","timestamp":1784557144799,"version":"3.55.0"},"reference-count":102,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:p>\n                    Twenty-five years ago, RET was identified as the primary driver of multiple endocrine neoplasia type 2 (MEN2) syndrome. MEN2 is characterized by several transformation events including pheochromocytoma, parathyroid adenoma and, especially penetrant, medullary thyroid carcinoma (MTC). Overall, MTC is a rare but aggressive type of thyroid cancer for which no effective treatment currently exists. Surgery, radiation, radioisotope treatment and chemotherapeutics have all shown limited success, and none of these approaches have proven durable in advanced disease. Non-mammalian models that incorporate the oncogenic RET isoforms associated with MEN2 and other RET-associated diseases have been useful in delineating mechanisms underlying disease progression. These models have also identified novel targeted therapies as single agents and as combinations. These studies highlight the importance of modeling disease in the context of the whole animal, accounting for the complex interplay between tumor and normal cells in controlling disease progression as well as response to therapy. With convenient access to whole genome sequencing data from expanded thyroid cancer patient cohorts, non-mammalian models will become more complex, sophisticated and continue to complement future mammalian studies. In this review, we explore the contributions of non-mammalian models to our understanding of thyroid cancer including MTC, with a focus on\n                    <jats:italic>Danio rerio<\/jats:italic>\n                    and\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    (fish and fly) models.\n                  <\/jats:p>","DOI":"10.1530\/erc-17-0411","type":"journal-article","created":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T20:20:21Z","timestamp":1516306821000},"page":"T91-T104","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":7,"title":["Non-mammalian models of multiple endocrine neoplasia type 2"],"prefix":"10.1530","volume":"25","author":[{"given":"Tirtha K","family":"Das","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross L","family":"Cagan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2018011817200994000_25.2.T91.1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203648"},{"key":"2018011817200994000_25.2.T91.2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20831"},{"key":"2018011817200994000_25.2.T91.3","doi-asserted-by":"crossref","first-page":"534","DOI":"10.2174\/1389450117666160301095233","article-title":"Polypharmacology of approved anticancer drugs","volume":"18","author":"Amelio","year":"2017","journal-title":"Current Drug Targets"},{"key":"2018011817200994000_25.2.T91.4","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.20728"},{"key":"2018011817200994000_25.2.T91.5","doi-asserted-by":"crossref","first-page":"13615","DOI":"10.1038\/ncomms13615","article-title":"Functional exploration of colorectal cancer genomes using drosophila","volume":"7","author":"Bangi","year":"2016","journal-title":"Nature Communications"},{"key":"2018011817200994000_25.2.T91.6","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/bs.acr.2016.01.006","article-title":"Emerging roles of epigenetic regulator Sin3 in cancer","volume":"130","author":"Bansal","year":"2016","journal-title":"Advances in Cancer Research"},{"key":"2018011817200994000_25.2.T91.7","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-2921"},{"key":"2018011817200994000_25.2.T91.8","first-page":"205","article-title":"Distribution of C cells in the normal and diseased thyroid gland","volume":"28","author":"Biddinger","year":"1993","journal-title":"Pathology Annual"},{"key":"2018011817200994000_25.2.T91.9","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1211604"},{"key":"2018011817200994000_25.2.T91.10","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-11-0099"},{"key":"2018011817200994000_25.2.T91.11","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1080\/17460441.2017.1297416","article-title":"Zebrafish xenograft models of cancer and metastasis for drug discovery","volume":"12","author":"Brown","year":"2017","journal-title":"Expert Opinion on Drug Discovery"},{"key":"2018011817200994000_25.2.T91.12","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-11-0351"},{"key":"2018011817200994000_25.2.T91.13","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.183"},{"key":"2018011817200994000_25.2.T91.14","first-page":"7284","article-title":"ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases","volume":"62","author":"Carlomagno","year":"2002","journal-title":"Cancer Research"},{"key":"2018011817200994000_25.2.T91.15","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2015.0334"},{"key":"2018011817200994000_25.2.T91.16","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.4.070802.110323"},{"key":"2018011817200994000_25.2.T91.17","doi-asserted-by":"crossref","first-page":"10351","DOI":"10.1038\/srep10351","article-title":"Invasiveness and metastasis of retinoblastoma in an orthotopic zebrafish tumor model","volume":"5","author":"Chen","year":"2015","journal-title":"Scientific Reports"},{"key":"2018011817200994000_25.2.T91.18","unstructured":"Cirello V Gaudenzi G Grassi ES Colombo C Vicentini L Ferrero S Persani L Vitale G Fugazzola L 2017 Tumor and normal thyroid spheroids: from tissues to zebrafish. 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