Telomere maintenance as a target for drug discovery.
The observation that the enzyme telomerase is up-regulated in 80-90% of cancer cells isolated from primary human tumors but is absent in neighboring cells of healthy tissue has resulted in significant efforts to validate telomerase as an anticancer drug target and to develop effective approaches toward its inhibition. In addition to inhibitors that target the enzymatic function of telomerase, efforts toward immunotherapy using peptides derived from its catalytic subunit hTERT and hTERT-promoter driven gene therapy have made significant advances. The increased level of telomerase in cancer cells also provides a potential platform for cancer diagnostics. Telomerase inhibition leads to disruption of a cell's ability to maintain the very ends of the chromosomes, which are called telomeres. Thus, the telomere itself has also attracted attention as an anticancer drug target. In this Perspective, interdisciplinary efforts to realize the therapeutic potential of targeting telomere maintenance with a focus on telomerase are discussed.
Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
Vijay
V
Sekaran
Joana
J
Soares
Michael B
MB
Jarstfer
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D054856:G-Quadruplexes / Q000187:drug effects; D018014:Gene Transfer Techniques; D006801:Humans; D007167:Immunotherapy; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000201:enzymology / Q000276:immunology / Q000628:therapy*; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*; D014158:Transcription, Genetic
D000970:Antineoplastic Agents; D019098:Telomerase