{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:07:56Z","timestamp":1792516076312,"version":"4.5.0"},"reference-count":85,"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                    Medullary thyroid carcinoma (MTC), a tumor derived from the neural crest, occurs either sporadically or as the dominant component of the type 2 multiple endocrine neoplasia (MEN) syndromes, MEN2A and MEN2B. The discovery that mutations in the\n                    <jats:italic>RET<\/jats:italic>\n                    protooncogene cause hereditary MTC was of great importance, since it led to the development of novel methods of diagnosis and treatment. For example, the detection of a mutated\n                    <jats:italic>RET<\/jats:italic>\n                    allele in family members at risk for inheriting MEN2A or MEN2B signaled that they would develop MTC, and possibly other components of the syndromes. Furthermore, the detection of a mutated allele created the opportunity, especially in young children, to remove the thyroid before MTC developed, or while it was confined to the gland. The discovery also led to the development of molecular targeted therapeutics (MTTs), mainly tyrosine kinase inhibitors, which were effective in the treatment of patients with locally advanced or metastatic MTC. While responses to MTTs are often dramatic, they are highly variable, and almost always transient, because the tumor cells become resistant to the drugs. Clinical investigators and the pharmaceutical industry are focusing on the development of the next generation of MTTs, which have minimal toxicity and greater specificity for mutated\n                    <jats:italic>RET<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1530\/erc-17-0325","type":"journal-article","created":{"date-parts":[[2017,11,15]],"date-time":"2017-11-15T20:25:15Z","timestamp":1510777515000},"page":"T1-T13","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":72,"title":["Advances in the management of MEN2: from improved surgical and medical treatment to novel kinase inhibitors"],"prefix":"10.1530","volume":"25","author":[{"given":"Samuel A","family":"Wells","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2018011817200996000_25.2.T1.1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.053959"},{"key":"2018011817200996000_25.2.T1.2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1827.2006.01942.x"},{"key":"2018011817200996000_25.2.T1.3","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.141.12.1199"},{"key":"2018011817200996000_25.2.T1.4","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0044"},{"key":"2018011817200996000_25.2.T1.5","doi-asserted-by":"publisher","DOI":"10.1210\/jc.78.1.114"},{"key":"2018011817200996000_25.2.T1.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6060(05)80057-1"},{"key":"2018011817200996000_25.2.T1.7","doi-asserted-by":"publisher","DOI":"10.1007\/s00104-011-2192-7"},{"key":"2018011817200996000_25.2.T1.8","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-007-9402-y"},{"key":"2018011817200996000_25.2.T1.9","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-11-0351"},{"key":"2018011817200996000_25.2.T1.10","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":"2018011817200996000_25.2.T1.11","first-page":"1076","article-title":"Parent-of-origin effects in multiple endocrine neoplasia type 2B","volume":"55","author":"Carlson","year":"1994","journal-title":"American Journal of Human Genetics"},{"key":"2018011817200996000_25.2.T1.12","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1111\/cen.12155","article-title":"An unusual genotype-phenotype correlation in MEN 2 patients: should screening for RET double germline mutations be performed to avoid misleading diagnosis and treatment?","volume":"79","author":"Cerutti","year":"2013","journal-title":"Clinical Endocrinology"},{"key":"2018011817200996000_25.2.T1.13","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.9566"},{"key":"2018011817200996000_25.2.T1.14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018380"},{"key":"2018011817200996000_25.2.T1.15","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3468(98)90433-X"},{"key":"2018011817200996000_25.2.T1.16","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1055\/s-0031-1279704","article-title":"Treatment of advanced medullary thyroid carcinoma with a combination of cyclophosphamide, vincristine, and dacarbazine: a single-center experience","volume":"119","author":"Deutschbein","year":"2011","journal-title":"Experimental and Clinical Endocrinology and Diabetes"},{"key":"2018011817200996000_25.2.T1.17","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/2.7.851"},{"key":"2018011817200996000_25.2.T1.18","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200104053441401"},{"key":"2018011817200996000_25.2.T1.19","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1714"},{"key":"2018011817200996000_25.2.T1.20","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.48.4659"},{"key":"2018011817200996000_25.2.T1.21","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.2.237"},{"key":"2018011817200996000_25.2.T1.22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1995.tb01903.x"},{"key":"2018011817200996000_25.2.T1.23","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/bjs.1800730411","article-title":"Familial medullary thyroid carcinoma without associated endocrinopathies: a distinct clinical entity","volume":"73","author":"Farndon","year":"1986","journal-title":"British Journal of Surgery"},{"key":"2018011817200996000_25.2.T1.24","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-0071"},{"key":"2018011817200996000_25.2.T1.25","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2001.01339.x"},{"key":"2018011817200996000_25.2.T1.26","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-06-0695"},{"key":"2018011817200996000_25.2.T1.27","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-111-10-802"},{"key":"2018011817200996000_25.2.T1.28","doi-asserted-by":"publisher","DOI":"10.1210\/jc.82.11.3902"},{"key":"2018011817200996000_25.2.T1.29","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197209)30:3<848::AID-CNCR2820300336>3.0.CO;2-2"},{"key":"2018011817200996000_25.2.T1.30","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0649"},{"key":"2018011817200996000_25.2.T1.31","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-19-1-152"},{"key":"2018011817200996000_25.2.T1.32","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1056\/NEJMoa1609324","article-title":"Long-term outcomes of imatinib treatment for chronic myeloid leukemia","volume":"376","author":"Hochhaus","year":"2017","journal-title":"New England Journal of Medicine"},{"key":"2018011817200996000_25.2.T1.33","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1899"},{"key":"2018011817200996000_25.2.T1.34","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1097\/00019616-199611000-00002","article-title":"The Sipple syndrome: from clinical description genetic analysis in the index family","volume":"6","author":"Hughes","year":"1996","journal-title":"Endocrinologist"},{"key":"2018011817200996000_25.2.T1.35","doi-asserted-by":"publisher","DOI":"10.1159\/000178893"},{"key":"2018011817200996000_25.2.T1.36","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-12-1106"},{"key":"2018011817200996000_25.2.T1.37","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2010.0328"},{"key":"2018011817200996000_25.2.T1.38","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.anl.2015.12.016","article-title":"Germline RET mutation carriers in Japanese patients with apparently sporadic medullary thyroid carcinoma: A single institution experience","volume":"43","author":"Kihara","year":"2016","journal-title":"Auris Nasus Larynx"},{"key":"2018011817200996000_25.2.T1.39","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.32.4145"},{"key":"2018011817200996000_25.2.T1.40","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1097\/00000658-199306000-00001","article-title":"Management of pheochromocytomas in patients with multiple endocrine neoplasia type 2 syndromes","volume":"217","author":"Lairmore","year":"1993","journal-title":"Annals of Surgery"},{"key":"2018011817200996000_25.2.T1.41","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.0068"},{"key":"2018011817200996000_25.2.T1.42","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-07-0667"},{"key":"2018011817200996000_25.2.T1.43","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1111\/j.1365-2796.1995.tb01209.x","article-title":"From medical history and biochemical tests to presymptomatic treatment in a large MEN 2A family","volume":"238","author":"Lips","year":"1995","journal-title":"Journal of Internal Medicine"},{"key":"2018011817200996000_25.2.T1.44","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1996.505292.x"},{"key":"2018011817200996000_25.2.T1.45","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/j.1365-2796.1995.tb01211.x","article-title":"Pheochromocytoma in multiple endocrine neoplasia type 2: European study. The Euromen Study Group","volume":"238","author":"Modigliani","year":"1995","journal-title":"Journal of Internal Medicine"},{"key":"2018011817200996000_25.2.T1.46","doi-asserted-by":"crossref","first-page":"549","DOI":"10.6004\/jnccn.2010.0042","article-title":"Medullary thyroid carcinoma: management of lymph node metastases","volume":"8","author":"Moley","year":"2010","journal-title":"Journal of the National Comprehensive Cancer Network"},{"key":"2018011817200996000_25.2.T1.47","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1921"},{"key":"2018011817200996000_25.2.T1.48","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-15-0070"},{"key":"2018011817200996000_25.2.T1.49","doi-asserted-by":"publisher","DOI":"10.1038\/363458a0"},{"key":"2018011817200996000_25.2.T1.50","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.12.2163"},{"key":"2018011817200996000_25.2.T1.51","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711720305"},{"key":"2018011817200996000_25.2.T1.52","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa071407"},{"key":"2018011817200996000_25.2.T1.53","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1365-2265.1989.tb03727.x","article-title":"Hereditary localized pruritus in affected members of a kindred with multiple endocrine neoplasia type 2A (Sipple\u2019s syndrome)","volume":"30","author":"Nunziata","year":"1989","journal-title":"Clinical Endocrinology"},{"key":"2018011817200996000_25.2.T1.54","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2010.0190"},{"key":"2018011817200996000_25.2.T1.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejso.2006.10.021"},{"key":"2018011817200996000_25.2.T1.56","doi-asserted-by":"crossref","first-page":"33993","DOI":"10.18632\/oncotarget.4992","article-title":"RET mutation p.S891A in a Chinese family with familial medullary thyroid carcinoma and associated cutaneous amyloidosis binding OSMR variant p.G513D","volume":"6","author":"Qi","year":"2015","journal-title":"Oncotarget"},{"key":"2018011817200996000_25.2.T1.57","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2009-0303"},{"key":"2018011817200996000_25.2.T1.58","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-2461"},{"key":"2018011817200996000_25.2.T1.59","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-008-9734-2"},{"key":"2018011817200996000_25.2.T1.60","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2010.03900.x"},{"key":"2018011817200996000_25.2.T1.61","doi-asserted-by":"publisher","DOI":"10.1038\/367377a0"},{"key":"2018011817200996000_25.2.T1.62","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2009.0021"},{"key":"2018011817200996000_25.2.T1.63","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s10689-016-9892-6","article-title":"MEN 2A-related cutaneous lichen amyloidosis: report of three kindred and systematic literature review of clinical, biochemical and molecular characteristics.","volume":"15","author":"Scapineli","year":"2016","journal-title":"Familial Cancer"},{"key":"2018011817200996000_25.2.T1.64","doi-asserted-by":"publisher","DOI":"10.1007\/BF01612635"},{"key":"2018011817200996000_25.2.T1.65","unstructured":"Schlumberger MJ Elisei R Bastholt L Wirth LJ Martins RG Locati LD Jarzab B Pacini F Daumerie C Droz JP , 2009 Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. Journal of Clinical Oncology 27 3794\u20133801. (https:\/\/doi.org\/10.1200\/JCO.2008.18.7815)"},{"key":"2018011817200996000_25.2.T1.66","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e318237480c"},{"key":"2018011817200996000_25.2.T1.67","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021713"},{"key":"2018011817200996000_25.2.T1.68","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1136\/gut.43.4.542","article-title":"Oncological implications of RET gene mutations in Hirschsprung\u2019s disease","volume":"43","author":"Sijmons","year":"1998","journal-title":"Gut"},{"key":"2018011817200996000_25.2.T1.69","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(61)90234-0"},{"key":"2018011817200996000_25.2.T1.70","first-page":"219","article-title":"Multiple endocrine neoplasia type 2 syndromes: historical perspectives","volume":"32","author":"Sipple","year":"1984","journal-title":"Henry Ford Hospital Medical Journal"},{"key":"2018011817200996000_25.2.T1.71","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043999"},{"key":"2018011817200996000_25.2.T1.72","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-196809000-00001"},{"key":"2018011817200996000_25.2.T1.73","first-page":"225","article-title":"Impact of screening on prognosis in the multiple endocrine neoplasia type 2 syndromes: natural history and treatment results in 105 patients","volume":"32","author":"Telenius-Berg","year":"1984","journal-title":"Henry Ford Hospital Medical Journal"},{"key":"2018011817200996000_25.2.T1.74","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.6004\/jnccn.2014.0169","article-title":"Thyroid carcinoma, version 2.2014.","volume":"12","author":"Tuttle","year":"2014","journal-title":"Journal of the National Comprehensive Cancer Network"},{"key":"2018011817200996000_25.2.T1.75","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2003.01782.x"},{"key":"2018011817200996000_25.2.T1.76","doi-asserted-by":"publisher","DOI":"10.1067\/msy.2001.118380a"},{"key":"2018011817200996000_25.2.T1.77","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.23.6604"},{"key":"2018011817200996000_25.2.T1.78","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.35.5040"},{"key":"2018011817200996000_25.2.T1.79","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1204"},{"key":"2018011817200996000_25.2.T1.80","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2014.0335"},{"key":"2018011817200996000_25.2.T1.81","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(54)90353-8"},{"key":"2018011817200996000_25.2.T1.82","doi-asserted-by":"publisher","DOI":"10.1002\/path.1700910109"},{"key":"2018011817200996000_25.2.T1.83","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19940115)73:2<432::AID-CNCR2820730231>3.0.CO;2-K"},{"key":"2018011817200996000_25.2.T1.84","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-11-0264"},{"key":"2018011817200996000_25.2.T1.85","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-08-0854"}],"container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/25\/2\/ERC-17-0325.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1530\/ERC-17-0325","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:54:27Z","timestamp":1784555667000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/25\/2\/T1-T13\/25278"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2]]},"references-count":85,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/erc-17-0325","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2]]}}}