{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T17:05:13Z","timestamp":1772471113626,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background and aim: Recent preclinical studies have confirmed that inhibiting the MAP kinase pathway can induce the re-differentiation of radioiodine (RAI)-refractory (RAIR) follicular cell thyroid cancers (TCs). The aim of this trial is to investigate whether the combination of kinase inhibitors (KIs) with myo-inositol (MI) can induce or potentiate the re-uptake of RAI in cancer cells. Overview and methods: This is an open label, non-pharmacological, multicenter, randomized pilot study. Patients will be divided into two groups: (1) a control group in which patients are treated with KIs (subgroup a: trametinib plus dabrafenib; subgroup b: lenvatinib); (2) a group in which patients (divided into the two subgroups) are treated with the same KIs in addition to MI. After 30 days of MI treatment, all patients, treated with levothyroxine (L-T4) at a semi-suppressive dosage as per clinical practice, will be stimulated with recombinant human TSH (rhTSH) (days 31 and 32). On day 35, the patients will be subjected to whole-body scintigraphy, with hybrid imaging where possible (SPECT\/CT), after the administration of diagnostic activity (185\u2013222 MBq of 123-I in accordance with the SNMMI\/EANM guidelines. Blood samples will be collected before starting MI therapy (day 0); after 30 days of MI therapy; and then on days 31, 32, 33, 34, and 35 after MI therapy. Quality of life (QoL) will be assessed at the beginning of the MI treatment and at the end of its administration. The primary endpoint is the restoration of 123-I uptake in RAIR-TC patients already on KI therapy alone and on KI therapy plus MI. The restoration of 123-I uptake in target lesions will be evaluated. Conclusions: MI may have a synergistic effect at the cellular level, and the possible increase in the re-differentiation of RAIR-TC in patients treated with KIs plus MI may have great clinical relevance. The re-uptake of RAI will be evaluated as the primary endpoint, and Tg values and QoL will be evaluated as the secondary endpoints. The main limitation of this study is that we do not investigate any clinical effects. We will have to postpone the clinical analysis to a later date after the administration of RAI for therapeutic purposes.<\/jats:p>","DOI":"10.3390\/life16030391","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T16:06:59Z","timestamp":1772467619000},"page":"391","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Treatment with Kinase Inhibitors Plus Myo-Inositol as Re-Differentiating Agents in Iodine-Refractory Thyroid Cancers"],"prefix":"10.3390","volume":"16","author":[{"given":"Carlotta","family":"Giani","sequence":"first","affiliation":[{"name":"Unit of Endocrinology, Azienda Usl-Toscana Nord-Ovest, 57121 Livorno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Russo","sequence":"additional","affiliation":[{"name":"R&D Department, Lo.Li. Pharma, Via Sabatino Gianni 14, 00156 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Lapi","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Azienda Usl-Toscana Nord-Ovest, 57121 Livorno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Antonietta","family":"Profilo","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Azienda Usl-Toscana Nord-Ovest, 57121 Livorno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaella","family":"Forleo","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Azienda Usl-Toscana Nord-Ovest, 57121 Livorno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Mazzi","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Azienda Usl-Toscana Nord-Ovest, 57121 Livorno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arianna","family":"Ghirri","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Azienda Usl-Toscana Nord-Ovest, 57121 Livorno, Italy"},{"name":"Department of Clinical and Experimental Medicine, Endocrinology Unit, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Caresia","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Azienda Usl-Toscana Nord-Ovest, 57121 Livorno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0177-939X","authenticated-orcid":false,"given":"Alfredo","family":"Campenn\u00ec","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, Unit of Nuclear Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1791-5915","authenticated-orcid":false,"given":"Cosimo","family":"Durante","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8167-4338","authenticated-orcid":false,"given":"Andrea","family":"Corsello","sequence":"additional","affiliation":[{"name":"Unit of Endocrine Surgery, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7783-0262","authenticated-orcid":false,"given":"Riccardo","family":"Morganti","sequence":"additional","affiliation":[{"name":"Section of Statistics, University Hospital of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vittorio","family":"Unfer","sequence":"additional","affiliation":[{"name":"Group on Inositol in Basic and Clinical Research and on PCOS (EGOI-PCOS), 00161 Rome, Italy"},{"name":"Department of Gynecology and Obstetrics, UniCamillus-Saint Camillus International University of Health Sciences, 00131 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa Maria","family":"Paragliola","sequence":"additional","affiliation":[{"name":"Departmental Faculty of Medicine, UniCamillus-Saint Camillus International University of Health Sciences, 00131 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Barbaro","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Azienda Usl-Toscana Nord-Ovest, 57121 Livorno, Italy"},{"name":"Group on Inositol in Basic and Clinical Research and on PCOS (EGOI-PCOS), 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s12022-022-09707-3","article-title":"Overview of the 2022 WHO Classification of Thyroid Neoplasms","volume":"33","author":"Baloch","year":"2022","journal-title":"Endocr. 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