HDAC as a Therapeutic Target for Treatment of Endometrial Cancers
| Autor: | Yuelang Zhang, Hongxia Wei, Jia Zhang, Dongli Zhao, Jiansheng Wang, Jinping Li, Zongfang Li, Juan Ren, Xiaozhi Zhang, Lisha Xiao, Jiansheng Qian, Yan Liu, Yi Li, Hui Cai, Hongbing Ma, Yan-e Gao, Rui Liu |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Tumor suppressor gene
Antineoplastic Agents Apoptosis Hydroxamic Acids Epigenesis Genetic Mice Drug Discovery medicine Animals Humans PTEN Gene Silencing Molecular Targeted Therapy Epigenetics Vorinostat Pharmacology biology Cancer DNA Methylation Cell cycle medicine.disease Endometrial Neoplasms Gene Expression Regulation Neoplastic Histone Deacetylase Inhibitors DNA methylation Cancer cell Cancer research biology.protein Female medicine.drug |
| Zdroj: | Current Pharmaceutical Design. 20:1847-1856 |
| ISSN: | 1381-6128 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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