[Importance of epigenetic changes in the thyroid cancer incidence and their therapeutic applications]

ABSTRACT

Thyroid cancer, the most common endocrine malignancy worldwide, originates from follicular epithelial cells. It is classified as a well-differentiated thyroid carcinoma [WDTC] -follicular [FTC] and papillary types [PTC]-, poorly differentiated thyroid carcinomas [PDTC], anaplastic thyroid carcinoma [ATC], and parafollicular calcitoninproducing cells include medullary thyroid carcinoma [MTC]. "Epigenetic" refers to the study of heritable changes in gene expression that occur without any alteration in the pattern of the primary DNA sequence. Growing evidence shows that epigenetic changes play important roles in thyroid carcinomas and, together with genetic changes, lead to tumorigenesis. Epigenetic silencing of various genes specific for thyroid differentiation have been detected in thyroid tumors. These changes in tumor-promoting and tumorsuppressor genes also contribute to the dysregulation of thyrocyte growth and other aspects of tumorigenesis. However, at present, no promising treatment is available for advanced thyroid cancer, which is unresponsive to radioiodine. Biologically targeted therapies for advanced thyroid carcinomas have been proposed based on the recognition of main oncogenic mutations. In this review we discuss the most frequent epigenetic variations in different types of thyroid cancer, epigenetic strategies for treating this carcinoma, and experimental data and clinical trials, particularly those that use deacetylase inhibitors and demethylating agents