Histone Deacetylase Inhibitors as Anticancer Drugs.
Histone Deacetylase Inhibitors as Anticancer Drugs.
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DOI：
10.3390/ijms18071414
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发表时间：
2017-07-01
影响因子：
5.6
通讯作者：
Hrabeta J
中科院分区：
文献类型：
--
作者：
Eckschlager T;Plch J;Stiborova M;Hrabeta J
致癌作用不能仅用遗传改变来解释，还涉及表观遗传过程。组蛋白乙酰化修饰在基因表达的表观遗传调控中起着关键作用，并由组蛋白去乙酰化酶（HDAC）和组蛋白乙酰转移酶（HAT）之间的平衡控制。HDAC抑制剂诱导癌细胞周期停滞、分化和细胞死亡，减少血管生成并调节免疫应答。HDAC抑制剂的抗癌作用机制并不统一;它们可能不同，并取决于癌症类型、HDAC抑制剂、剂量等。HDAC抑制剂似乎是有前途的抗癌药物，特别是在与其他抗癌药物和/或放射治疗联合使用时。HDAC抑制剂伏立诺他、罗米地辛和贝利司他已被批准用于一些T细胞淋巴瘤，帕比司他用于多发性骨髓瘤。其他HDAC抑制剂正在临床试验中用于治疗血液和实体恶性肿瘤。这些研究的结果是有希望的，但需要进一步的更大规模的研究。由于癌症发展过程中表观遗传变化的可逆性，表观遗传疗法的效力似乎非常重要。在这里，我们总结了不同类别的HDAC抑制剂的数据，其作用机制，并讨论了临床前和临床研究的新结果，包括与其他治疗方式的组合。
Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.
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DOI：
10.1080/15384101.2015.1042634
发表时间：
2015
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Bhaskara S
通讯作者：
Bhaskara S
影响因子：
3.9
作者：
Brest, Patrick;Lassalle, Sandra;Hofman, Paul
通讯作者：
Hofman, Paul
影响因子：
11.2
作者：
Adams CM;Hiebert SW;Eischen CM
通讯作者：
Eischen CM
Vorinostat与Bortezomib结合的I阶段研究，用于复发和难治性多发性骨髓瘤。
影响因子：
11.5
作者：
Badros, Ashraf;Burger, Angelika M.;Philip, Sunita;Niesvizky, Ruben;Kolla, Sarah S.;Goloubeva, Olga;Harris, Carolynn;Zwiebel, James;Wright, John J.;Espinoza-Delgado, Igor;Baer, Maria R.;Holleran, Julianne L.;Egorin, Merrill J.;Grant, Steven
通讯作者：
Grant, Steven
影响因子：
5.3
作者：
Balliu M;Guandalini L;Romanelli MN;D'Amico M;Paoletti F
通讯作者：
Paoletti F