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Targeting histone deacetylase in thyroid cancer

机译：针对甲状腺癌的组蛋白脱乙酰基酶

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Introduction: 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. Areas covered: 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. Expert opinion: 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.
机译：简介：已在甲状腺癌细胞中检测到表观遗传学变化，证据表明它们可能有助于改变这些细胞的分化和增殖。组蛋白乙酰化/去乙酰化代表了调节基因表达的主要机制，包括与肿瘤转化有关的基因，在许多临床前研究中，抑制组蛋白去乙酰化酶（HDAC）活性的药物均显示出令人鼓舞的抗肿瘤活性。涵盖的领域：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学改变。然后，本综述着重于临床前和临床研究（有些仍在进行中）的结果，其中已使用HDAC抑制剂（HDACi）治疗甲状腺癌。专家意见：HDAC是甲状腺癌治疗的潜在重要靶标。抑制HDAC活性已产生令人鼓舞的结果，就降低增殖速率和恢复转化甲状腺细胞中的碘吸收能力而言。 HDACi，尤其是与其他分子靶向药物联合使用时，对于那些对当前可用治疗无反应的肿瘤可能是一个重要的选择。

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