Journal
ONCOGENE
Volume 21, Issue 4, Pages 631-637Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1205063
Keywords
telomerase; oligonucleotides; 2 '-methoxyethyl RNA; telomere
Funding
- NCI NIH HHS [P50CA70907, CA 85363] Funding Source: Medline
- NIGMS NIH HHS [GM 60642] Funding Source: Medline
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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.
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