组蛋白去乙酰化酶抑制剂在抗肿瘤应用中的进展

Development of histone deacetylase inhibitor in antitumor study

人类完整基因组的研究已取得了巨大的进展，但基因表达调控的研究仍然处于初步阶段。研究发现，包括肿瘤在内的许多疾病与某些基因表达的失活有关。导致基因失活的表观遗传机制主要包括DNA甲基化、组蛋白乙酰化和染色质高级结构中其他成分的修饰，这些修饰改变染色质构型，导致基因转录调节发生变化，基因转录的失调导致细胞增殖失常，从而致癌。这些可逆失活的基因如果重新表达可能抑制肿瘤生长。组蛋白去乙酰化酶抑制剂正是基于这种思路被应用于包括甲状腺癌在内多种肿瘤研究，并为失分化甲状腺癌的再分化及放射性碘治疗提供了一条新的研究途径。

Human genome project has made a great progress, but the study about the gene expression regulation is still at the beginning. It＇ s found that many diseases such as cancer are related to the deactivation of some gene expressions, whose epigenetic mechanisms involve DNA methylation, histone acetylation and other structural changes in chromatin. That disturbs the normal gene expression regulation and cell multiplication, which finally induce the carcinogenesis. So the re-expression of inactive genes may play a part in inhibiting the carcinogenesis. On the basis of the view, histone deaeetylase （HDAC） inhibitor has a variety of applications in the study of disease and tumor, including the thyroid carcinoma. Furthermore, it comtribute to the mew way of the redifferentication and radioidine therapy against poorly differentiated thyroid carcinoma.