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Open AccessReview

Molecular Alterations in Thyroid Cancer: From Bench to Clinical Practice

1
Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
2
Center of Experimental Oncology and Hematology, A.O.U. Policlinico-Vittorio Emanuele, 95123 Catania, Italy
3
Department of Medical Oncology A.O.U. Policlinico-Vittorio Emanuele, 95123 Catania, Italy
4
Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Catania, Garibaldi-Nesima Medical Center, 95122 Catania, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Genes 2019, 10(9), 709; https://doi.org/10.3390/genes10090709
Received: 12 July 2019 / Revised: 26 August 2019 / Accepted: 10 September 2019 / Published: 13 September 2019
(This article belongs to the Special Issue Thyroid Cancer: Genetics and Targeted Therapies)
Thyroid cancer comprises different clinical and histological entities. Whereas differentiated (DTCs) malignancies are sensitive to radioiodine therapy, anaplastic (ATCs) and medullary (MTCs) tumors do not uptake radioactive iodine and display aggressive features associated with a poor prognosis. Moreover, in a majority of DTCs, disease evolution leads to the progressive loss of iodine sensitivity. Hence, iodine-refractory DTCs, along with ATCs and MTCs, require alternative treatments reflective of their different tumor biology. In the last decade, the molecular mechanisms promoting thyroid cancer development and progression have been extensively studied. This has led to a better understanding of the genomic landscape, displayed by thyroid malignancies, and to the identification of novel therapeutic targets. Indeed, several pharmacological compounds have been developed for iodine-refractory tumors, with four multi-target tyrosine kinase inhibitors already available for DTCs (sorafenib and lenvatinib) and MTCs (cabozantib and vandetanib), and a plethora of drugs currently being evaluated in clinical trials. In this review, we will describe the genomic alterations and biological processes intertwined with thyroid cancer development, also providing a thorough overview of targeted drugs already tested or under investigation for these tumors. Furthermore, given the existing preclinical evidence, we will briefly discuss the potential role of immunotherapy as an additional therapeutic strategy for the treatment of thyroid cancer. View Full-Text
Keywords: differentiated thyroid cancer; anaplastic thyroid cancer; medullary thyroid cancer; radioactive iodine resistance; molecular alterations; targeted therapy; tyrosine kinase inhibitors; mTOR inhibitors; immunotherapy; clinical trials differentiated thyroid cancer; anaplastic thyroid cancer; medullary thyroid cancer; radioactive iodine resistance; molecular alterations; targeted therapy; tyrosine kinase inhibitors; mTOR inhibitors; immunotherapy; clinical trials
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Tirrò, E.; Martorana, F.; Romano, C.; Vitale, S.R.; Motta, G.; Di Gregorio, S.; Massimino, M.; Pennisi, M.S.; Stella, S.; Puma, A.; Gianì, F.; Russo, M.; Manzella, L.; Vigneri, P. Molecular Alterations in Thyroid Cancer: From Bench to Clinical Practice. Genes 2019, 10, 709.

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