{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T23:39:43Z","timestamp":1788565183084,"version":"build-2803163510"},"reference-count":70,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T00:00:00Z","timestamp":1663027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health (IRCCS funding Ricerca Corrente, ZEBRANET)","award":["PRIN 2017Z3N3YC"],"award-info":[{"award-number":["PRIN 2017Z3N3YC"]}]},{"name":"Italian Ministry of Education, University and Research","award":["PRIN 2017Z3N3YC"],"award-info":[{"award-number":["PRIN 2017Z3N3YC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor arising from parafollicular C cells of the thyroid gland. In this preclinical study, we tested three tyrosine-kinase inhibitors (TKIs): SU5402, a selective inhibitor of fibroblast growth factor receptor (FGFR)-1 and vascular endothelial growth factor receptor (VEGFR)-2; sulfatinib, an inhibitor of FGFR-1 and VEGFR-1, -2, -3; and SPP86, a RET-specific inhibitor. The effects of these compounds were evaluated in vitro in two human MTC cell lines (TT and MZ-CRC-1), and in vivo using xenografts of MTC cells in zebrafish embryos. SU5402, sulfatinib and SPP86 decreased cell viability. Sulfatinib and SPP86 significantly induced apoptosis in both cell lines. Sulfatinib and SPP86 inhibited the migration of TT and MZCRC-1 cells, while SU5402 was able to inhibit migration only in TT cells. In vivo we observed a significant reduction in TT cell-induced angiogenesis in zebrafish embryos after incubation with sulfatinib and SPP86. In conclusion, sulfatinib and SPP86 displayed a relevant antitumor activity both in vitro and in vivo. Moreover, this work suggests the potential utility of targeting FGFR and VEGFR signaling pathways as an alternative therapy for MTC.<\/jats:p>","DOI":"10.3390\/cancers14184442","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T21:06:52Z","timestamp":1663103212000},"page":"4442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Preclinical Evaluation of Novel Tyrosine-Kinase Inhibitors in Medullary Thyroid Cancer"],"prefix":"10.3390","volume":"14","author":[{"given":"Davide","family":"Saronni","sequence":"first","affiliation":[{"name":"PhD Program in Experimental Medicine, University of Milan, 20100 Milan, Italy"},{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germano","family":"Gaudenzi","sequence":"additional","affiliation":[{"name":"Laboratory of Geriatric and Oncologic Neuroendocrinology Research, Istituto Auxologico Italiano IRCCS, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0887-5242","authenticated-orcid":false,"given":"Alessandra","family":"Dicitore","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Carra","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Celeste","family":"Cantone","sequence":"additional","affiliation":[{"name":"Laboratory of Geriatric and Oncologic Neuroendocrinology Research, Istituto Auxologico Italiano IRCCS, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8967-9678","authenticated-orcid":false,"given":"Maria Orietta","family":"Borghi","sequence":"additional","affiliation":[{"name":"Experimental Laboratory of Immuno-Rheumatology, Istituto Auxologico Italiano IRCCS, 20100 Milan, Italy"},{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4696-7404","authenticated-orcid":false,"given":"Andrea","family":"Barbieri","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9958-1225","authenticated-orcid":false,"given":"Luca","family":"Mignani","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo J.","family":"Hofland","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus MC, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2068-9581","authenticated-orcid":false,"given":"Luca","family":"Persani","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy"},{"name":"Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2478-683X","authenticated-orcid":false,"given":"Giovanni","family":"Vitale","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy"},{"name":"Laboratory of Geriatric and Oncologic Neuroendocrinology Research, Istituto Auxologico Italiano IRCCS, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,13]]},"reference":[{"key":"ref_1","first-page":"481","article-title":"Procalcitonin as a Marker of Medullary Thyroid Carcinoma","volume":"46","year":"2021","journal-title":"Minerva Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"338","DOI":"10.3747\/co.26.5539","article-title":"Diagnosis and Pathologic Characteristics of Medullary Thyroid Carcinoma-Review of Current Guidelines","volume":"26","author":"Thomas","year":"2019","journal-title":"Curr. 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