{"id":1326,"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\/hsp90-inhibition-as-a-novel-therapeutic-approach-for-the-treatment-of-aggressive-thyroid-carcinomas\/"},"modified":"2026-01-24T08:35:20","modified_gmt":"2026-01-24T08:35:20","slug":"hsp90-inhibition-as-a-novel-therapeutic-approach-for-the-treatment-of-aggressive-thyroid-carcinomas","status":"publish","type":"post","link":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/hsp90-inhibition-as-a-novel-therapeutic-approach-for-the-treatment-of-aggressive-thyroid-carcinomas\/","title":{"rendered":"HSP90 INHIBITION AS A NOVEL THERAPEUTIC APPROACH FOR THE TREATMENT OF AGGRESSIVE THYROID CARCINOMAS"},"content":{"rendered":"
McMillin W.D.1<\/sup>, Kotoula V.2<\/sup>, Negri J.1<\/sup>, Hayden P.1<\/sup>, Koletsa T.2<\/sup>, Mitsiades S.C.1<\/sup>, Mitsiades N.1, 3<\/sup><\/div>\n
1<\/sup>Department of Medical Oncology, Dana Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston MA, USA, 2<\/sup>Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece, 3<\/sup>Memorial Sloan Kettering Cancer Center, New York, USA<\/div>\n
\n

Abstract<\/h2>\n

Context:<\/strong> Hsp90 is a molecular chaperone that interacts with several intracellular proteins, such as Akt, IGF1R, Raf, etc, to facilitate their proper folding and preserve their correct 3-dimensional conformation and functional status. Hsp90 inhibitors (e.g.17- allylamino- 17-demethoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG)) have shown promising anticancer activity and are undergoing clinical evaluation.
Objective – Methods:<\/strong> We investigated the effect of 17-AAG and 17-DMAG (Calbiochem, San Diego, CA) on a panel of 6 thyroid carcinoma cell lines with MTT assay, flow cytometry, gene expression profiling, RT-PCR and immunoblotting. The DNA binding activity of p53 was quantified by enzyme linked immunosorbent assay (ELISA) using the Trans-AMT p53 Transcription Factor Assay Kit (Active Motif, Carlsbad, CA). PRIMA-1 (p53 Reactivation and Induction of Massive Apoptosis), a cell-permeable small molecule that can restore the activity of mutant p53, was from Calbiochem.
Results:<\/strong> Both 17-DMAG and 17-AAG induced growth arrest and apoptosis in vitro in thyroid carcinoma cells, including those of anaplastic and medullary origin, suppressed Akt, IGF1R and B-Raf expression, upregulated Hsp90 expression and induced caspase-3 and PARP cleavage. Apoptosis induced by 17-DMAG was partially abrogated by the caspase inhibitor ZVAD-FMK, as well as by transfection of myristoylated (constitutively active) Akt orBcl-2 cDNA. 17-DMAG suppressed p53 expression and DNA-binding activity, as well as expression of the p53-dependent pro-apoptotic molecules Bax, Noxa and PUMA. Concurrent treatment with the p53 activator PRIMA-1 or the DNA-damaging chemotherapeutic doxorubicin enhanced 17-DMAG-induced apoptosis.
Conclusions:<\/strong> Hsp90 inhibitors suppress the expression of several proliferative\/anti-apoptotic mediators and induce growth arrest and caspase-dependent apoptosis in thyroid carcinomas. Hsp90 chaperones p53, and Hsp90 inhibition suppresses p53 expression and activity. Reactivation of p53, such as with the small molecule PRIMA-1 or with DNA-damaging chemotherapy may sensitize 17-DMAG-treated thyroid carcinoma cells to apoptosis. These findings have direct implications for the development of novel combination therapies for aggressive thyroid carcinomas. <\/div>\n","protected":false},"excerpt":{"rendered":"

McMillin W.D.1, Kotoula V.2, Negri J.1, Hayden P.1, Koletsa T.2, Mitsiades S.C.1, Mitsiades N.1, 3 1Department of Medical Oncology, Dana Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston MA, USA, 2Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece, 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-1326","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\/1326","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=1326"}],"version-history":[{"count":0,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts\/1326\/revisions"}],"wp:attachment":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/media?parent=1326"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/categories?post=1326"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/tags?post=1326"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}