Telomerase: a potential therapeutic target for cancer

被引:20
作者
Fletcher, TM [1 ]
机构
[1] Univ Miami, Sch Med, Dept Biochem & Mol Biol, Miami, FL 33136 USA
关键词
G-quadruplex; hTERC; hTERT; telomerase; telomere;
D O I
10.1517/14728222.9.3.457
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Telomeres are complex structures which serve to protect chromosome ends. Telomere shortening occurs in normal somatic cells reaching a point in which cells senesce. Senescence can be counteracted by activating telomerase. Telomerase activity is present in a majority of cancer cells and requires the upregulation of the reverse transcriptase component called hTERT. Because telomerase activity is essential for proliferation of most cancer cells, therapeutic strategies have been developed to inhibit its activity. These strategies centre on targeting the active site, hTERT and hTERC expression, core enzyme stability and telomeric DNA. Successful approaches involve a combination of traditional drugs with telomerase inhibitors. Disrupting the functional expression of hTERT is particularly effective in agreement with evidence that hTERT is an antiapoptotic factor in some cancer cells. In addition, approaches that stabilise DNA secondary structures may disrupt telomere maintenance through a variety of routes making them, potentially, very potent in attacking cancer cells.
引用
收藏
页码:457 / 469
页数:13
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