{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:42:09Z","timestamp":1792014129793,"version":"4.4.0"},"reference-count":38,"publisher":"Bioscientifica","issue":"8","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                    <jats:p\/>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Medullary thyroid cancer (MTC) is a rare cancer, accounting for 2\u20133% of all thyroid cancers. Point mutations in the RET proto-oncogene can be detected in 25\u201365% of MTC. These mutations commonly occur in the cysteine-rich or tyrosine kinase domains, leading to constitutively active tyrosine kinase activity in RET. In the last decade, significant advancements have been made in treating MTC with the advent of tyrosine kinase inhibitors, especially in RET-mutated MTC. Multikinase inhibitors such as vandetanib and cabozantinib were the first few effective inhibitors, which have been shown to slow disease progression in the treatment of advanced MTC. In more recent years, these have been followed by highly selective RET inhibitors selpercatinib and pralsetinib, which have made their way into the clinic, demonstrating high efficacy and a more favourable side-effect profile due to their reduction in off-target effects. In spite of these successes, there remains a continued need to develop strategies to overcome treatment resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/erc-24-0291","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T14:23:15Z","timestamp":1753971795000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":6,"title":["Targeting RET in medullary thyroid cancer"],"prefix":"10.1530","volume":"32","author":[{"given":"Kate","family":"Newbold","sequence":"first","affiliation":[{"name":"Thyroid Unit, The Royal Marsden NHS Foundation Trust , ,","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3981-897X","authenticated-orcid":true,"given":"Leslie","family":"Cheng","sequence":"additional","affiliation":[{"name":"Thyroid Unit, The Royal Marsden NHS Foundation Trust , ,","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"2026070905432667300_bib1","doi-asserted-by":"crossref","first-page":"E364","DOI":"10.1210\/jc.2012-2703","article-title":"Exomic sequencing of medullary thyroid cancer reveals dominant and mutually exclusive oncogenic mutations in RET and RAS","volume":"98","author":"Agrawal","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070905432667300_bib2","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1200\/PO.20.00096","article-title":"Systemic and CNS activity of selective RET inhibition with selpercatinib (LOXO-292) in a patient with RET-mutant medullary thyroid cancer with extensive CNS metastases","volume":"4","author":"Andreev-Drakhlin","year":"2020","journal-title":"JCO Precis Oncol"},{"key":"2026070905432667300_bib3","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1089\/thy.2013.0137","article-title":"In vitro and in vivo activity of cabozantinib (XL184), an inhibitor of RET, MET, and VEGFR2, in a model of medullary thyroid cancer","volume":"23","author":"Bentzien","year":"2013","journal-title":"Thyroid"},{"key":"2026070905432667300_bib4","doi-asserted-by":"crossref","first-page":"E2031","DOI":"10.1210\/jc.2012-2092","article-title":"Somatic RAS mutations occur in a large proportion of sporadic RET-negative medullary thyroid carcinomas and extend to a previously unidentified exon","volume":"97","author":"Boichard","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070905432667300_bib5","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.isci.2019.09.030","article-title":"Genetic landscape of somatic mutations in a large cohort of sporadic medullary thyroid carcinomas studied by next-generation targeted sequencing","volume":"20","author":"Ciampi","year":"2019","journal-title":"iScience"},{"key":"2026070905432667300_bib6","doi-asserted-by":"crossref","first-page":"213","DOI":"10.4137\/CMO.S6197","article-title":"Vandetanib (ZD6474) in the treatment of medullary thyroid cancer","volume":"5","author":"Deshpande","year":"2011","journal-title":"Clin Med Insights Oncol"},{"key":"2026070905432667300_bib7","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1210\/jc.2007-1714","article-title":"Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study","volume":"93","author":"Elisei","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070905432667300_bib8","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1200\/JCO.2012.48.4659","article-title":"Cabozantinib in progressive medullary thyroid cancer","volume":"31","author":"Elisei","year":"2013","journal-title":"J Clin Oncol"},{"key":"2026070905432667300_bib9","article-title":"Highlights of prescribing information: GAVRETO\u2122 (pralsetinib). 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