Oncology Unit, Third Department of Internal Medicine, Sotiria General Hospital, Athens University School of Medicine, 152 Mesogeion Av., 11527, Athens, Greece.
Cancer Chemother Pharmacol. 2013 Nov;72(5):935-52. doi: 10.1007/s00280-013-2223-9. Epub 2013 Sep 14.
Deoxyribonucleic acid is wrapped around an octamer of core histone proteins to form a nucleosome, the basic structure of chromatin. Two main families of enzymes maintain the equilibrium of acetyl groups added to or removed from lysine residues. Histone deacetylases (HDACs) catalyze the removal of acetyl groups from lysine residues in histone amino termini and non-histone proteins also, leading to chromatin condensation and transcriptional repression. HDAC overexpression, resulting in tumor suppressor genes silencing, has been found in several human cancer tissues, indicating that aberrant epigenetic activity is associated with cancer development. Therefore, inhibitors of these enzymes are emerging anticancer agents and there is evidence supporting their role in hematological malignancies. The minimal efficacy of conventional chemotherapy has prompted a renewed focus on targeted therapy based on pathways altered during the pathogenesis of lung cancer. We identify the pleiotropic antitumor effects of HDAC inhibitors in lung cancer, focusing on the result caused by their use individually, as well as in combination with other chemotherapeutic agents, in lung cancer cell lines and in clinical trials.
We searched reviews and original papers in Pubmed over the last 10 years.
We identified 76 original papers on this topic.
Numerous preclinical studies have shown that HDAC inhibitors exhibit impressive antitumor activity in lung cancer cell lines. Nevertheless, Phase III randomized studies do not support HDAC inhibitors use in lung cancer patients in everyday practice. Ongoing and future studies would help determine their role in lung cancer treatment.
脱氧核糖核酸围绕核心组蛋白八聚体形成核小体，这是染色质的基本结构。两种主要的酶家族维持赖氨酸残基上添加或去除乙酰基的平衡。组蛋白去乙酰化酶（HDACs）催化赖氨酸残基上的乙酰基从组蛋白氨基末端和非组蛋白蛋白上的去除，导致染色质浓缩和转录抑制。在几种人类癌症组织中发现了 HDAC 的过度表达，导致肿瘤抑制基因沉默，这表明异常的表观遗传活性与癌症的发展有关。因此，这些酶的抑制剂是新兴的抗癌药物，有证据表明它们在血液恶性肿瘤中发挥作用。传统化疗的疗效有限，促使人们重新关注基于肺癌发病机制中改变的途径的靶向治疗。我们确定了 HDAC 抑制剂在肺癌中的多效抗肿瘤作用，重点关注它们单独使用以及与其他化疗药物联合使用在肺癌细胞系和临床试验中的结果。
我们在过去 10 年的 Pubmed 中搜索了综述和原始论文。
我们确定了 76 篇关于这个主题的原始论文。
大量的临床前研究表明，HDAC 抑制剂在肺癌细胞系中表现出令人印象深刻的抗肿瘤活性。然而，III 期随机研究不支持在日常实践中在肺癌患者中使用 HDAC 抑制剂。正在进行和未来的研究将有助于确定它们在肺癌治疗中的作用。
