Epigenetics Modifications and Therapeutic Prospects in Human Thyroid Cancer
نویسندگان
چکیده
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.
منابع مشابه
درمان سرطان بر پایه اپی ژنتیک
Introduction: Epigenetics involves the study of heritable changes in the regulation of gene activity and expression that are not dependent on gene sequence. Main mechanisms of epigenetic modifications are DNA methylation, Histone modification and Nucleosome positioning. Several studies have shown that these modifications are related to cancer initiation, progression or tumor metastasis. In cont...
متن کاملRole of Epigenetics in Biology and Human Diseases
For a long time, scientists have tried to describe disorders just by genetic or environmental factors. However, the role of epigenetics in human diseases has been considered from a half of century ago. In the last decade, this subject has attracted many interests, especially in complicated disorders such as behavior plasticity, memory, cancer, autoimmune disease, and addiction as well as neurod...
متن کاملInvestigation of selective CDK4/6 inhibitor (Abemaciclib) cytotoxicity effects on human anaplastic thyroid cancer
Background: Thyroid cancer is one of the most common endocrine malignancies. Anaplastic thyroid cancer is a rare and dead full cancer among types of the thyroid cancer. Despite the conventional chemotherapy, a considerable number of the patients show developing chemo resistance. Therefore, there is a necessary need to find the novel therapeutic approaches in the anaplastic thyroid cancer patien...
متن کاملThe importance of epigenetic modifications in cancer progression
Epigenetics are dynamic and inherited changes in the genome that occur independently of DNA sequencing. This phenomenon requires coherent interaction with various enzymes and other molecular components. Abnormal epigenetic changes can lead to the onset of improper gene expression and the promotion of tumorigenesis. Because epigenetic changes are prone to external and reversible factors, they ar...
متن کامل