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首页> 外文会议>Weissenburg Symposium Biriciana >Azanudeoside DNA Methyltransferase Inhibitor Drugs: Update on Clinical Applications in Myelodysplastic Syndromes and Acute Myeloid Leukemia
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Azanudeoside DNA Methyltransferase Inhibitor Drugs: Update on Clinical Applications in Myelodysplastic Syndromes and Acute Myeloid Leukemia

机译：硫代稳产苷DNA甲基转移酶抑制剂药物：更新骨髓增生综合征和急性髓性白血病的临床应用

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The cytidine analog 5-azacytidine (5-aza, Vidaza) and its deoxyribonu-cleoside analog 5-aza-2'-deoxycytidine (decitabine, Dacogen), while first synthesized and shown to have interesting antileukemic activity in 1964, have only recently been FDA and EMA approved for the treatment of myelodysplastic syndromes (MDS; 5-aza by FDA and EMA, decitabine by FDA) and acute myeloid leukemia (AML) of older patients unfit for intensive chemotherapy (EMA). These drugs therefore constitute a novel treatment standard for the mostly elderly patients with these hematologic malignancies. The clinical development of active, low-toxic schedules of these drugs (favoring DNA hypomethylation over immediate cytotox-icity) has taken an arduous route: for decades, this mechanism of action was not generally accepted. However, eventually, the proof of their clinical activity even at low doses-together with the recent discovery of recurrent somatic mutations of multiple epigenetic modifier genes in AML-has in turn lent credence to the fundamental role of DNA methylation abnormalities in cancer in general. This chapter provides an update of the clinical development and current state of both drugs as single agents for MDS, AML, and other hematopoietic malignancies, particularly as a novel, well-tolerated treatment option for older and unfit patients with comorbidities. In addition, combination treatments with other epigenetically active agents are described, and direct comparisons between the two drugs are reviewed. Finally, an integrated treatment approach is emerging where leukemia and MDS patients fit for allogeneic blood stem cell transplantation are being "bridged" to this curative treatment by hypome'thylating treatment as a milder, better-tolerated alternative to standard, aggressive chemotherapy.
机译：胞苷类似物5-氮杂胞苷（5-AZA，VIDAZA）及其脱氧豆核糖苷e类似物5-AZA-2'-脱氧胞苷（Dexa-2'-脱氧胞苷（Defitabine，Docogen），同时在1964年首次合成并显示有有趣的抗血糖活动，最近才有FDA和EMA批准用于治疗骨髓增强症综合征（MDS; 5-AZA通过FDA和EMA，FDA的Defitabine）和急性髓性白血病（AML）的老年患者不适合强化化疗（EMA）。因此，这些药物为这些血液学恶性肿瘤的大多数老年患者构成了一种新的治疗标准。这些药物的活性，低毒时间表的临床发展（有利于DNA低甲基化在即时细胞毒毒性）所取得艰巨的路线：几十年来，通常不接受这种作用机制。然而，最终，即使在低剂量下，它们的临床活性的证明与最近发现的AML中的多个表观遗传改性剂基因的复发体细胞突变 - 已经缺乏信任，这是癌症中DNA甲基化异常的基本作用。本章提供了对MDS，AML和其他造血恶性肿瘤的单一药剂的临床开发和当前状态的更新，特别是对于老年人和不合适的患者的组合患者的新颖，耐受性耐受性的治疗选择。此外，描述了与其他外观活性剂的组合处理，并审查两种药物之间的直接比较。最后，综合治疗方法正在出现综合治疗方法，其中白血病和MDS患者适合同种异体血液干细胞移植的患者是通过缺点的处理作为这种疗法处理的疗效，作为一种温和，耐受性化疗的较高，耐受性化疗的较高替代性。

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