Telomerase inhibition, oligonucleotides, and clinical trials.
Telomerase is expressed in most types of tumors but not in most somatic cells. This observation has led to two hypotheses; (i) telomerase activity is necessary for the proliferation of cancer cells; and (ii) telomerase inhibitors are a powerful strategy for cancer chemotherapy. Testing the latter hypothesis requires the development of potent and selective inhibitors of telomerase and their testing in clinical trials. Assaying the efficacy of telomerase inhibitors will not be simple because telomere erosion will be slow and antiproliferative effects will probably require weeks to become apparent. This review will describe the properties of 2'-O-alkyl oligonucleotide inhibitors of telomerase. Oligonucleotides that block expression of other cancer targets have favorable pharmacokinetic properties and are already in clinical trials. This experience is likely to facilitate clinical trials of anti-telomerase oligomers.
Corey
David R
DR
Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, TX 75390-9041, USA. david.corey@utsothwestern.edu
D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000201:enzymology / Q000628:therapy*; D009841:Oligonucleotides / Q000737:chemistry / Q000627:therapeutic use*; D009843:Oligoribonucleotides; D016372:RNA, Antisense / Q000494:pharmacology; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics
C119446:2'-O-(2-methoxyethyl)-RNA; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009841:Oligonucleotides; D009843:Oligoribonucleotides; D016372:RNA, Antisense; D019098:Telomerase