{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:22:00Z","timestamp":1792552920113,"version":"4.5.0"},"reference-count":45,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>No data are available about the possible association of TP53 mutations and the response to multikinase inhibitors (MKIs) in thyroid cancer (TC).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We evaluated the effect of TP53 mutations on the response to lenvatinib (LEN) in advanced TCs and in vitro models.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We investigated the molecular profile, including TP53 mutations, of 30 tumor tissues from patients treated with LEN, and tested p53 status by immunohistochemistry. These data were compared with clinical-pathological features, and tumor response to LEN. The response to LEN was also evaluated in TP53-defective and TP53-proficient TC cell lines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>TP53 mutations significantly correlated with a poor response to LEN (P = .005). TP53-mutated patients had a shorter progression-free survival (PFS) (P &amp;lt; .0001) and overall survival (OS) rates (P = .0007). Accordingly, patients harboring altered nuclear p53 protein expression had shorter PFS and OS (P = .0001 and P = .0056, respectively). These data were confirmed in a validation cohort. In accordance with clinical data, TC cell lines with p53 alterations had low or null sensitivity, while those with TP53 wild-type showed different degrees of sensitivity, primarily due to the increased number of tumor cells in G1 phase, consistent with the cytostatic effect of LEN.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We show for the first time in advanced TC that the presence of TP53 alterations is a predictor of poor response to LEN treatment and is associated with worse PFS and OS rates. The evaluation of TP53 mutations\/p53 expression might be included in the patient\/tumor characterization to be performed before starting an MKI treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf056","type":"journal-article","created":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T11:03:41Z","timestamp":1738407821000},"page":"e3353-e3365","source":"Crossref","is-referenced-by-count":5,"title":["TP53 Alterations Are Associated With Poor Response to Lenvatinib in Patients With Advanced Thyroid Cancer"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8795-5226","authenticated-orcid":false,"given":"Valentina","family":"Cirello","sequence":"first","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Endocrine Oncology Unit, IRCCS Istituto Auxologico Italiano , Milan 20149 ,","place":["Italy"]},{"name":"Department of Pathophysiology and Transplantation, University of Milan , Milan 20122 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Health Sciences, Unit of Human Pathology, Santi Paolo e Carlo Medical School, University of Milan , Milan 20141 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7416-4644","authenticated-orcid":false,"given":"Giacomo","family":"Gazzano","sequence":"additional","affiliation":[{"name":"Pathology Unit, IRCCS Istituto Auxologico Italiano , Milan 20095 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3715-0737","authenticated-orcid":false,"given":"Stefano","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Division of Pathology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico , Milan 20122 ,","place":["Italy"]},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan , Milan 20122 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