[Inhibition of telomeres and telomerase. Seeking for new anticancer drugs].
Human telomeres are guanine-rich regions (TTAGGG) located at the end of chromosomes that protect them against aberrant recombination and protect DNA from exonuclease degradation. Telomeres maintenance is performed by telomerase, a RNA-dependent DNA polymerase. Telomerase is over-expressed in a large number of cancers that have short telomeres whereas it is not expressed in somatic cells that have long telomeres. Therefore, this differential gives a rational for further evaluation of telomerase and telomeres as targets for identification of new anticancer drugs. Current strategies aim to identify new drugs with specific activity against telomerase and telomeres. In this review we will discuss the biological and clinical approaches as well as relevant tumor models for studying the biological effects of telomerase inhibition and telomere targeting in vitro and in vivo.
Raymond
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Translational Research Laboratory, Institute for Drug Development, San Antonio, Texas 78245-3217, USA.
Faivre
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S
Dieras
V
V
Von Hoff
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D
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D004273:DNA, Neoplasm; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics*; D009698:Nucleoproteins / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000187:drug effects* / Q000235:genetics
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D009698:Nucleoproteins; D018894:Reverse Transcriptase Inhibitors; D019098:Telomerase
Inhibition des télomères et de la télomérase. Recherche de nouveaux médicaments anticancéreux.