Fletcher Terace M
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, 1011 NW 15 Street, Miami, FL 33136, USA.
Expert Opin Ther Targets. 2005 Jun;9(3):457-69. doi: 10.1517/14728222.9.3.457.
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 attack-ing cancer cells.
端粒是用于保护染色体末端的复杂结构。端粒缩短发生在正常体细胞中，直至细胞衰老。衰老可通过激活端粒酶来对抗。大多数癌细胞中存在端粒酶活性，这需要上调称为hTERT的逆转录酶成分。由于端粒酶活性对大多数癌细胞的增殖至关重要，因此已开发出抑制其活性的治疗策略。这些策略集中在靶向活性位点、hTERT和hTERC表达、核心酶稳定性和端粒DNA。成功的方法包括将传统药物与端粒酶抑制剂联合使用。破坏hTERT的功能表达特别有效，这与hTERT在某些癌细胞中是抗凋亡因子的证据一致。此外，稳定DNA二级结构的方法可能通过多种途径破坏端粒维持，使其在攻击癌细胞方面可能非常有效。
