Incles Christopher M, Schultes Christoph M, Neidle Stephen
Cancer Research UK Biomolecular Structure Group, School of Pharmacy, University of London, 29-39 Brunswick Square, London, WC1N 1AX, UK.
Curr Opin Investig Drugs. 2003 Jun;4(6):675-85.
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.
染色体末端(端粒)在正常体细胞中会逐渐缩短,最终导致不可逆的生长停滞。相比之下,所有癌细胞中的端粒长度稳定,并通过端粒酶有效地实现永生化,端粒酶催化端粒DNA重复序列的合成。人们已经设计了几种抑制端粒酶的策略,希望这能产生抗癌效果。本文综述并严格评估了催化抑制剂、针对模板的反义核酸以及DNA底物折叠等主要方法在抗癌治疗中的潜力。