ROMIDEPSIN FOR THE TREATMENT OF CUTANEOUS T-CELL LYMPHOMA
ROMIDEPSIN FOR THE TREATMENT OF CUTANEOUS T-CELL LYMPHOMA
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DOI：
10.1358/dot.2009.45.11.1437052
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发表时间：
2009-11-01
期刊：
影响因子：
1.8
通讯作者：
Campas-Moya, Clara
中科院分区：
文献类型：
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作者：
Campas-Moya, Clara
通过组蛋白去乙酰化的异常表观遗传基因调控与肿瘤发生有关。组蛋白去乙酰化酶（HDAC）抑制剂是一种正在研究和开发的有前途的抗癌药物。罗米地辛是一种新型的有效HDAC抑制剂，即使在纳摩尔浓度下也能高效抑制HDAC活性。与II类相比，它在I类HDAC酶中表现出相当强的直接抑制作用。除了组蛋白脱乙酰化，罗米地辛还调节参与癌症起始和进展的其他靶点，如c-myc、Hsp 90和p53。罗米地辛通过诱导细胞凋亡、细胞分化和细胞周期阻滞，在多种非临床肿瘤模型中显示出良好的体外和体内抗癌作用。罗米地辛最近已被FDA批准用于治疗先前接受过最好的全身治疗的皮肤T细胞淋巴瘤（CTCL）患者。目前正在进行临床研究，用于治疗其他血液系统恶性肿瘤和实体瘤，作为单药治疗或与其他抗癌药物联合治疗。
Aberrant epigenetic gene regulation by deacetylation of histone proteins has been involved in tumorigenesis. Histone deacetilase (HDAC) inhibitors ore promising anticancer agents under research and development. Romidepsin is a novel and potent HDAC inhibitor highly efficient in inhibiting HDAC activity even at nanomolar concentrations. It exhibits a considerably stronger direct inhibition in class I HDAC enzymes os compared to class II. In addition of histone deacetylation, romidepsin modulates additionol targets involved in cancer initiation and progression such os c-myc, Hsp90 ond p53. Romidepsin has shown promising anticancer effects in a wide variety of nonclinical cancer models both in vitro ond in vivo by induction of apoptosis, cell differentiation ond cell cycle arrest. Romidepsin has been recently approved by the FDA for the treatment of cutaneous T-cell lymphoma (CTCL) patients who have received at beast one prior systemic therapy. It is currently under clinical investigation for the treatment of other hematological malignances and solid tumors as monotherapy and in combination with other anticancer agents.