University Magna Graecia of Catanzaro, Department of Health Sciences, Campus S. Venuta, 88100 Catanzaro, Italy.
Expert Opin Ther Targets. 2013 Feb;17(2):179-93. doi: 10.1517/14728222.2013.740013. Epub 2012 Dec 13.
Epigenetic changes have been detected in thyroid cancer cells, and evidence indicates that they may contribute to altered differentiation and proliferation of these cells. Histone acetylation/deacetylation represents a major mechanism for modulating the expression of genes, including those involved in neoplastic transformation, and drugs that inhibit histone deacetylase (HDAC) activity have displayed promising anti-tumor activity in many pre-clinical studies.
We provide a brief overview of the mechanisms underlying histone acetylation-mediated regulation of gene expression and the principal epigenetic alterations detected in thyroid cancer cells. The review then focuses on the results of pre-clinical and clinical studies (some still underway) in which HDAC inhibitors (HDACi) have been used to treat thyroid cancer.
HDACs are a potentially important target for thyroid cancer treatments. Inhibition of HDAC activity has produced encouraging results in terms of reducing proliferation rates and restoring the iodine-uptake capacity in transformed thyrocytes. HDACi, especially when combined with other molecularly targeted drugs, may represent an important option for those tumors that are unresponsive to the currently available treatments.
在甲状腺癌细胞中已经检测到表观遗传变化，有证据表明这些变化可能导致这些细胞分化和增殖的改变。组蛋白乙酰化/去乙酰化是调节基因表达的主要机制，包括参与肿瘤转化的基因，并且抑制组蛋白去乙酰化酶（HDAC）活性的药物在许多临床前研究中显示出有希望的抗肿瘤活性。
我们简要概述了组蛋白乙酰化介导的基因表达调控的机制，以及在甲状腺癌细胞中检测到的主要表观遗传改变。然后，本综述重点介绍了使用 HDAC 抑制剂（HDACi）治疗甲状腺癌的临床前和临床研究（一些仍在进行中）的结果。
HDAC 是甲状腺癌治疗的一个潜在重要靶点。抑制 HDAC 活性在降低增殖率和恢复转化甲状腺细胞的碘摄取能力方面产生了令人鼓舞的结果。HDACi，特别是与其他分子靶向药物联合使用，可能是对目前可用治疗方法无反应的肿瘤的一个重要选择。
