Telomerase: a potential therapeutic target for cancer.
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.
Fletcher
Terace M
TM
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, 1011 NW 15 Street, Miami, FL 33136, USA. tfletcher@med.miami.edu
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016615:Telomere / Q000201:enzymology / Q000235:genetics
D000970:Antineoplastic Agents; D019098:Telomerase