Small molecule HDAC inhibitors: Promising agents for breast cancer treatment

被引:54
作者
Huang, Meiling [1 ]
Zhang, Jian [2 ]
Yan, Changjiao [1 ]
Li, Xiaohui [3 ]
Zhang, Juliang [1 ]
Ling, Rui [1 ]
机构
[1] Fourth Mil Med Univ, Xijing Hosp, Dept Thyroid Breast & Vasc Surg, Xian 710032, Shaanxi, Peoples R China
[2] Fourth Mil Med Univ, Xijing Hosp, Dept Burns & Cutaneous Surg, Xian 710032, Shaanxi, Peoples R China
[3] Dalian Univ Technol, Sch Life Sci & Biotechnol, Dalian 116024, Peoples R China
基金
中国国家自然科学基金;
关键词
HDACs; HDAC inhibitors; Anticancer drug; Breast cancer; Clinical trials; HISTONE DEACETYLASE INHIBITOR; SUBEROYLANILIDE HYDROXAMIC ACID; PHASE-II; ANTITUMOR-ACTIVITY; CELLS; EXPRESSION; SAHA; VORINOSTAT; ENTINOSTAT; LBH589;
D O I
10.1016/j.bioorg.2019.103184
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Breast cancer, a heterogeneous disease, is the most frequently diagnosed cancer and the second leading cause of cancer-related death among women worldwide. Recently, epigenetic abnormalities have emerged as an important hallmark of cancer development and progression. Given that histone deacetylases (HDACs) are crucial to chromatin remodeling and epigenetics, their inhibitors have become promising potential anticancer drugs for research. Here we reviewed the mechanism and classification of histone deacetylases (HDACs), association between HDACs and breast cancer, classification and structure-activity relationship (SAR) of HDACIs, pharmacokinetic and toxicological properties of the HDACIs, and registered clinical studies for breast cancer treatment. In conclusion, HDACIs have shown desirable effects on breast cancer, especially when they are used in combination with other anticancer agents. In the coming future, more multicenter and randomized Phase III studies are expected to be conducted pushing promising new therapies closer to the market. In addition, the design and synthesis of novel HDACIs are also needed.
引用
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页数:13
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