{"id":1324,"date":"2026-01-24T08:35:20","date_gmt":"2026-01-24T08:35:20","guid":{"rendered":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/anti-tumor-effects-of-the-tyrosine-kinase-inhibitors-sunitinib-su11248-and-vandetanib-zd6474-in-huma\/"},"modified":"2026-01-24T08:35:20","modified_gmt":"2026-01-24T08:35:20","slug":"anti-tumor-effects-of-the-tyrosine-kinase-inhibitors-sunitinib-su11248-and-vandetanib-zd6474-in-huma","status":"publish","type":"post","link":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/anti-tumor-effects-of-the-tyrosine-kinase-inhibitors-sunitinib-su11248-and-vandetanib-zd6474-in-huma\/","title":{"rendered":"ANTI-TUMOR EFFECTS OF THE TYROSINE KINASE INHIBITORS SUNITINIB (SU11248) AND VANDETANIB (ZD6474) IN HUMAN THYROID CARCINOMA CELL LINES"},"content":{"rendered":"
Charalambous E.1,2<\/sup>, Kotoula V.1<\/sup>, Hayden P.2<\/sup>, McMillin W.D.2<\/sup>, Negri J.2<\/sup>, Mitsiades S.C.2<\/sup>, Mitsiades N.2, 3<\/sup><\/div>\n
1<\/sup>Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece, 2<\/sup>Department of Medical Oncology, Dana Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston MA, USA., 3<\/sup>Memorial Sloan Kettering Cancer Center, New York, USA<\/div>\n
\n

Abstract<\/h2>\n

Context:<\/strong> The Ret kinase is overactive and participates in the pathogenesis of a subset of thyroid carcinomas. Specifically, some papillary and anaplastic carcinomas harbor RET\/PTC translocations, whereas medullary carcinomas harbor point mutations of RET. Sunitinib (SU11248: Sutent, Pfizer), an oral tyrosine kinase inhibitor (TKI), targets the vascular endothelial growth factor receptors (VEGFRs), platelet derived growth factor receptor (PDGFR), stem-cell factor receptor, Fms-like tyrosine kinase receptor 3 and Ret receptor tyrosine-kinases. Vandetanib (ZD6474; Zactima,AstraZeneca) is an orally bioavailable, well-tolerated, inhibitor of VEGFR-2, EGFR and Ret.
Objective\/Methods:<\/strong> Using flow cytometry and MTT assay, we evaluated the effect of sunitinib and vandetanib on the viability of a panel of 20 thyroid carcinoma cell lines (papillary, follicular, anaplastic and medullary) in vitro. The human anaplastic thyroid carcinoma cell line FRO was stably transfected with cDNA for Bcl-2 or constitutively active (myristoylated) Akt and subsequently evaluated for sensitivity to sunitinib and vandetanib.
Results:<\/strong> Sunitinib and vandetanib induced growth arrest in all thyroid carcinoma cell lines tested, including those of medullary and anaplastic origin, as shown by MTT and flow cytometry, yet were more effective against cell lines harboring a RET\/PTC translocation. Both TKIs suppressed phosphorylation of MEK, MAPK and STAT3, yet prolonged (>24 h) exposure to TKI resulted in rebound in MAPK phosphorylation and did not achieve greater antiproliferative effect. This can be attributed to downregulation of expression of DUSP6, a phosphatase responsible for dephosphorylating MAPK.Intermittent, pulsatile exposure to TKI had similar anti-cancer activity as continuous treatment. The TKI effect was not attenuated by overexpression ofBcl-2 or constitutively active Akt.
Conclusions:<\/strong> Ret is an important target for the treatment of thyroid carcinoma. The TKIs sunitinib and vandetanib exhibit antitumor activity against thyroid carcinoma cells in vitro, especially those with overactivated Ret, suggesting that they are promising candidates for further clinical evaluation. <\/div>\n","protected":false},"excerpt":{"rendered":"

Charalambous E.1,2, Kotoula V.1, Hayden P.2, McMillin W.D.2, Negri J.2, Mitsiades S.C.2, Mitsiades N.2, 3 1Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece, 2Department of Medical Oncology, Dana Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston MA, USA., 3Memorial Sloan Kettering Cancer Center, New York, USA Abstract Context: Read More<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[45,2,9],"tags":[],"class_list":["post-1324","post","type-post","status-publish","format-standard","hentry","category-volume-7-issue-3","category-journal-articles","category-volume-7"],"_links":{"self":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts\/1324","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/comments?post=1324"}],"version-history":[{"count":0,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts\/1324\/revisions"}],"wp:attachment":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/media?parent=1324"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/categories?post=1324"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/tags?post=1324"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}