Telomere maintenance mechanisms as a target for drug development.
The shortening of the telomeric DNA sequences at the ends of chromosomes is thought to play a critical role in regulating the lifespan of human cells. Since all dividing cells are subject to the loss of telomeric sequences, cells with long proliferative lifespans need mechanisms to maintain telomere integrity. It appears that the activation of the enzyme telomerase is the major mechanism by which these cells maintain their telomeres. The proposal that a critical step in the process of the malignant transformation of cells is the upregulation of expression of telomerase has made this enzyme a potentially useful prognostic and diagnostic marker for cancer, as well as a new target for therapeutic intervention for the treatment of patients with cancer. It is now clear that simply inhibiting telomerase may not result in the anticancer effects that were originally hypothesized. While telomerase may not be the universal target for cancer therapy, we certainly believe that targeting the telomere maintenance mechanisms will be important in future research aimed toward a successful strategy for curing cancer.
Bearss
D J
DJ
The Arizona Cancer Center, The University of Arizona, Tucson 85724, USA.
Hurley
L H
LH
Von Hoff
D D
DD
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D015195:Drug Design; D006026:Glycoside Hydrolases / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000201:enzymology; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D010569:Perylene / Q000031:analogs & derivatives; D010880:Piperidines / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012313:RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000037:antagonists & inhibitors; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D038501:Tankyrases; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000502:physiology; D016615:Telomere / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology
D000873:Anthracenes; D000970:Antineoplastic Agents; D006026:Glycoside Hydrolases; D016376:Oligonucleotides, Antisense; D010569:Perylene; D010880:Piperidines; D011065:Poly(ADP-ribose) Polymerases; D012313:RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D018894:Reverse Transcriptase Inhibitors; D038501:Tankyrases; D019098:Telomerase; C116108:N,N'-bis(2-1(piperidino)-ethyl)-3,4,9,10-perylene-tetracarboxylic diimide; C422952:telomerase RNA; C418109:TNKS protein, human; C022407:poly ADP-ribose glycohydrolase