title: Treatment of advanced thyroid cancer with targeted therapies: ten years of experience.
abstract: Thyroid cancer is rare, but it is the most frequent endocrine malignancy. Its prognosis is generally favorable, especially in cases of well-differentiated thyroid cancers (DTCs), such as papillary and follicular cancers, which have survival rates of approximately 95% at 40 years. However, 15-20% of cases became radioiodine refractory (RAI-R), and until now, no other treatments have been effective. The same problems are found in cases of poorly differentiated (PDTC) and anaplastic (ATC) thyroid cancers and in at least 30% of medullary thyroid cancer (MTC) cases, which are very aggressive and not sensitive to radioiodine. Tyrosine kinase inhibitors (TKIs) represent a new approach to the treatment of advanced cases of RAI-R DTC, MTC, PDTC, and, possibly, ATC. In the past 10 years, several TKIs have been tested for the treatment of advanced, progressive, and RAI-R thyroid tumors, and some of them have been recently approved for use in clinical practice: sorafenib and lenvatinib for DTC and PDTC and vandetanib and cabozantinib for MTC. The objective of this review is to present the current status of the treatment of advanced thyroid cancer with the use of innovative targeted therapies by describing both the benefits and the limits of their use based on the experiences reported so far. A comprehensive analysis and description of the molecular basis of these therapies, as well as new therapeutic perspectives, are reported. Some practical suggestions are given for both the choice of patients to be treated and their management, with particular regard to the potential side effects.
authors.affiliation: Department of Clinical and Experimental MedicineSection of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Viola
authors.affiliation: Department of Clinical and Experimental MedicineSection of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Valerio
authors.affiliation: Department of Clinical and Experimental MedicineSection of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Molinaro
authors.affiliation: Department of Clinical and Experimental MedicineSection of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Agate
authors.affiliation: Department of Clinical and Experimental MedicineSection of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Bottici
authors.affiliation: Department of Clinical and Experimental MedicineSection of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Biagini
authors.affiliation: Department of Clinical and Experimental MedicineSection of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Lorusso
authors.affiliation: Department of Clinical and Experimental MedicineSection of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Cappagli
authors.affiliation: Department of Clinical and Experimental MedicineSection of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Pieruzzi
authors.affiliation: Department of Clinical and Experimental MedicineSection of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Giani
authors.affiliation: Department of Clinical and Experimental MedicineSection of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Sabini
authors.affiliation: Department of Clinical and Experimental MedicineSection of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Passannati
authors.affiliation: Department of Clinical and Experimental MedicineSection of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Puleo
authors.affiliation: Department of Clinical and Experimental MedicineSection of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Matrone
authors.affiliation: Diagnostic and Interventional RadiologyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Pontillo-Contillo
authors.affiliation: Diagnostic and Interventional RadiologyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Battaglia
authors.affiliation: Diagnostic and Interventional RadiologyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Mazzeo
authors.affiliation: Department of Clinical and Experimental MedicineSection of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.affiliation: Department of Clinical and Experimental MedicineSection of Endocrinology, University of Pisa, Pisa, Italy rossella.elisei@med.unipi.it.
authors.forename: Rossella
authors.initials: R
authors.lastname: Elisei
mesh_terms: D000818:Animals; D006801:Humans; D058990:Molecular Targeted Therapy; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics
keywords: BRAF; RET; advanced thyroid cancer; targeted therapy; tyrosine kinase inhibitors