Prospects for anti-neoplastic therapies based on telomere biology.
The maintenance of specialized nucleoprotein structures at the ends of human chromosomes called telomeres is essential for chromosome stability, and plays a fundamental role in the regulation of cellular lifespan. Without new synthesis of telomeres, chromosome ends shorten with progressive cell division, eventually triggering either replicative senescence or apoptosis when telomere length becomes critically short. The regulation of telomerase activity in human cells plays a significant role in the development of cancer. Telomerase is tightly repressed in the vast majority of normal human somatic cells but becomes activated during cell immortalization and in cancers. Recent work has demonstrated that inhibiting or targeting telomerase shows promise as a novel anti-neoplastic strategy; however, the biology of telomeres and telomerase predict that such approaches will differ in important ways from traditional cytotoxic drug therapies. Understanding telomerase biology may eventually lead to several types of clinically effective, telomerase-based therapies for neoplastic disease.
Stewart
Sheila A
SA
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Hahn
William C
WC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000502:physiology; D016615:Telomere / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology
D000970:Antineoplastic Agents; D019098:Telomerase