罗咪酯肽
伏立诺他
表观遗传学
组蛋白脱乙酰基酶
生物
癌变
去肽
癌症
癌症研究
表观遗传疗法
癌细胞
组蛋白脱乙酰酶抑制剂
组蛋白
遗传学
基因
DNA甲基化
基因表达
生物化学
作者
Astrid Hagelkrüys,Anna Sawicka,Magdalena Rennmayr,Christian Seiser
出处
期刊:Handbook of experimental pharmacology
日期:2011-01-01
卷期号:: 13-37
被引量:93
标识
DOI:10.1007/978-3-642-21631-2_2
摘要
Traditionally, cancer has been regarded to originate from genetic alterations such as mutations, deletions, rearrangements as well as gene amplifications, leading to abnormal expression of tumor suppressor genes and oncogenes. An increasing body of evidence indicates that in addition to changes in DNA sequence, epigenetic alterations contribute to cancer initiation and progression. In contrast to genetic mutations, epigenetic changes are reversible and therefore an attractive target for cancer therapy. Many epi-drugs such as histone deacetylase (HDAC) inhibitors showed anticancer activity in cell culture and animal models of carcinogenesis. Recently, the two HDAC inhibitors suberoylanilide hydroxamic acid (SAHA, Vorinostat) and Romidepsin (Depsipeptide, FK228) were FDA approved for the treatment of cutaneous T-cell lymphoma (CTCL). Although HDAC inhibitors are potent anticancer agents, these compounds act against several HDAC family members potentially resulting in numerous side effects. This stems from the fact that HDACs play crucial roles in a variety of biological processes including cell cycle progression, proliferation, differentiation, and development. Consistently, mice deficient in single HDACs mostly exhibit severe phenotypes. Therefore, it is necessary to specify the cancer-relevant HDACs in a given tumor type in order to design selective inhibitors that target only cancer cells without affecting normal cells. In this chapter, we summarize the current state of knowledge of individual nuclear HDAC family members in development and tumorigenesis, their contribution to the hallmarks of cancer, and the involvement of HDAC family members in different types of human malignancies.
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