Abstract
At present no successful treatment is available for advanced thyroid cancer, which comprises poorly differentiated, anaplastic, and metastatic or recurrent differentiated thyroid cancer not responding to radioiodine. In the last few years, biologically targeted therapies for advanced thyroid carcinomas have been proposed on the basis of the recognition of key oncogenic mutations. Although the results of several phase II trials look promising, none of the patients treated had a complete response, and only a minority of them had a partial response, suggesting that the treatment is, at best, effective in stabilizing patients with progressive disease. “Epigenetic” refers to the study of heritable changes in gene expression that occur without any alteration in the primary DNA sequence. The epigenetic processes establish and maintain the global and local chromatin states that determine gene expression. Epigenetic abnormalities are present in almost all cancers and, together with genetic changes, drive tumor progression. Various genes involved in the control of cell proliferation and invasion (p16INK4A, RASSF1A, PTEN, Rap1GAP, TIMP3, DAPK, RARβ2, E-cadherin, and CITED1) as well as genes specific of thyroid differentiation (Na+/I− symport, TSH receptor, pendrin, SL5A8, and TTF-1) present aberrant methylation in thyroid cancer. This review deals with the most frequent epigenetic alterations in thyroid cancer and focuses on epigenetic therapy, whose goal is to target the chromatin in rapidly dividing tumor cells and potentially restore normal cell functions. Experimental data and clinical trials, especially using deacetylase inhibitors and demethylating agents, are discussed.
Highlights
Thyroid carcinoma is the most common endocrine malignancy worldwide, its incidence being approximately 1–5% of all cancers in females and less than 2% in males
Thyroid carcinomas arising from follicular epithelial cells are traditionally classified as well-differentiated thyroid carcinomas (WDTC), including both papillary (PTC, 80%) and follicular types (FTC, 10–15%; Fassnacht et al, 2009), poorly differentiated thyroid carcinomas (PDTC; Patel and Shaha, 2006; Ghossein, 2009) and, anaplastic thyroid carcinoma (ATC), accounting for 1–2% of thyroid malignancies
In 2004 we demonstrated that valproic acid induces Na+/I− symporter (NIS) gene expression, NIS membrane localization, and iodide accumulation in poorly differentiated thyroid cancer cells (Fortunati et al, 2004)
Summary
Thyroid carcinoma is the most common endocrine malignancy worldwide, its incidence being approximately 1–5% of all cancers in females and less than 2% in males. Even though it is considered a relatively rare neoplasm, its incidence is progressively increasing (Kilfoy et al, 2009). Chemotherapy is generally taken into consideration only for patients with symptomatic or rapidly progressive metastatic disease unresponsive to or unsuitable for surgery, radioiodine, and external beam radiotherapy; but the efficacy of cytotoxic systemic chemotherapies for these tumors is fairly poor, response rates being around 25% or less (Sherman, 2010). RET/PTC rearrangement, distinctive of PTC, has not been identified in FA or FTC, supporting divergent tumor induction/progression www.frontiersin.org
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
