Title:HDAC as a Therapeutic Target for Treatment of Endometrial Cancers
Volume: 20
Issue: 11
Author(s): Hongbing Ma, Jinping Li, Hongxia Wei, Yan Liu, Jiansheng Qian, Rui Liu, Lisha Xiao, Yan-e Gao, Jiansheng Wang, Juan Ren, Zongfang Li, Dongli Zhao, Xiaozhi Zhang, Yuelang Zhang, Yi Li, Hui Cai and Jia Zhang
Affiliation:
Keywords:
Histone deacetylases, endometrial cancers, Inhibitors, therapeutic target.
Abstract: Accumulating evidence suggested that epigenetic changes such as promoter-specific DNA hypermethylation and histone
deacetylation cause tumor suppressor gene silencing and contribute to malignant transformation. Treatment of cancer cells with HDAC
inhibitors can reactivate the expression of silenced genes, block the cell cycle, and induce cell apoptosis. In vitro experiments in cancer
cell cultures and in vivo studies using mouse xynograft model have shown that HDAC inhibitors deliver potent anti-cancer effects. Clinical
trials have led to approval of SAHA (Vorinostat) for treatment of lymphoma. Endometrial cancer (EC) is the most frequent malignancy
in women’s reproductive tract. EC is known for extensive epigenetic alterations, including overexpression of HDAC and DNMT
enzymes, and the frequent epigenetic silencing of DNA repair genes such as MLH1, tumor suppressor genes PTEN, and progesterone receptor,
which suggests a potentially high sensitivity of this type of cancer to HDAC inhibitors. Indeed, studies from many laboratories using
various models have shown that HDAC inhibitors are promising chemotherapy reagents for endometrial cancers. This review summarizes
the results from these studies, with an emphasis to provide an update on the new findings from new drugs. Background information
on HDAC expression in EC, and features of HDAC inhibitors are presented based on their relevance to our focused topic. The combined
application of HDAC inhibitors with radiation therapy and other conventional therapeutic reagents are also discussed.
