Telomerase inhibitors in cancer therapy: current status and future directions.
The ends of chromosomes (telomeres) are subject to progressive shortening in normal somatic cells, leading ultimately to irreversible growth arrest. In contrast, telomeres in all cancer cells are stabilized in length and effectively immortalized by the enzyme telomerase, which catalyzes the synthesis of telomeric DNA repeats. Several strategies have been devised for the inhibition of telomerase in the hope that this will result in anticancer effects. The principal approaches of catalytic inhibitors, antisense to the template, and folding of the DNA substrate, are reviewed and critically evaluated for their potential in anticancer therapy.
Incles
Christopher M
CM
Cancer Research UK Biomolecular Structure Group, School of Pharmacy, University of London, 29-39 Brunswick Square, London, WC1N 1AX, UK.
Schultes
Christoph M
CM
Neidle
Stephen
S
D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005544:Forecasting; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016615:Telomere / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D019098:Telomerase