DNA demethylating antineoplastic strategies: a comparative point of view.
DNA demethylating antineoplastic strategies: a comparative point of view.
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DOI：
10.1177/1947601910365081
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发表时间：
2010-03-01
期刊：
影响因子：
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通讯作者：
Fanelli, Mirco
中科院分区：
文献类型：
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作者：
Amatori, Stefano;Bagaloni, Irene;Fanelli, Mirco
尽管基因改变参与了肿瘤细胞的转化，但越来越明显的是，异常的表观遗传模式，如那些影响DNA甲基化和组蛋白翻译后修饰(PTM)的模式，在肿瘤发展的早期阶段发挥着重要作用。这一发现，加上表观遗传变化是可逆的证据，使被称为表观遗传疗法的新的抗肿瘤治疗方法的发展成为可能。表观遗传修饰参与了基因表达的控制，它们的异常分布被认为通过导致关键细胞途径的放松调控而参与了肿瘤转化。表观遗传药物能够逆转癌细胞的缺陷基因表达谱，从而重建正常的分子通路。考虑到表观遗传疗法的新兴趣，本文重点介绍了影响DNA甲基化的方法，评估了新的策略和那些已被批准用于临床的策略，并比较了它们的治疗潜力。
Despite the involvement of genetic alterations in neoplastic cell transformation, it is increasingly evident that abnormal epigenetic patterns, such as those affecting DNA methylation and histone posttranslational modifications (PTMs), play an essential role in the early stages of tumor development. This finding, together with the evidence that epigenetic changes are reversible, enabled the development of new antineoplastic therapeutic approaches known as epigenetic therapies. Epigenetic modifications are involved in the control of gene expression, and their aberrant distribution is thought to participate in neoplastic transformation by causing the deregulation of crucial cellular pathways. Epigenetic drugs are able to revert the defective gene expression profile of cancer cells and, consequently, reestablish normal molecular pathways. Considering the emerging interest in epigenetic therapeutics, this review focuses on the approaches affecting DNA methylation, evaluates novel strategies and those already approved for clinical use, and compares their therapeutic potential.