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Preclinical and clinical strategies for development of telomerase and telomere inhibitors Sharma S; Raymond E; Soda H; Sun D; Hilsenbeck SG; Sharma A; Izbicka E; Windle B; Von Hoff DDAnn Oncol 1997[Nov]; 8 (11): 1063-74BACKGROUND: Telomerase is an important enzyme whose activity has been convincingly demonstrated in humans recently. It is required for maintenance of ends of chromosomes (telomeres) during cell division. Since its presence has been selectively demonstrated in dividing cells including tumor cells, it has generated considerable excitement as a potential anti-cancer strategy. DESIGN: In this article, we review the current relevant biology of the enzyme, the challenges encountered in the preclinical phase of target development and the current efforts that focus on telomeres and telomerase as therapeutic targets. We also speculate on the potential toxicities and mechanisms of resistance that may be encountered during use of such therapies.|*Telomerase/antagonists & inhibitors/metabolism/therapeutic use[MESH]|Animals[MESH]|Breast Neoplasms/enzymology/etiology/genetics[MESH]|Cell Survival/physiology[MESH]|Cell Transformation, Neoplastic[MESH]|DNA Replication/physiology[MESH]|DNA, Neoplasm/*genetics[MESH]|Female[MESH]|Humans[MESH]|In Vitro Techniques[MESH]|Male[MESH]|Neoplasms/drug therapy/*enzymology[MESH]|Polymerase Chain Reaction[MESH]|Prostatic Neoplasms/enzymology/etiology/genetics[MESH]|Telomere/*enzymology/ultrastructure[MESH] |
