Role of telomerase in cancer therapeutics

Kyung H. Choi, Michel M Ouellette

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Telomerase is responsible for the maintenance of telomeres, specialized structures that cap the ends of chromosomes. Because most human cells lack telomerase, telomeres shorten each time cells divide and this attrition acts as a clock that limits their lifespan. During cancer development, this limited lifespan is almost always bypassed by the reactivation of telomerase, the enzyme responsible for the synthesis of telomeres. This upregulation of telomerase provides the cancer cells with cellular immortality or ability to proliferate for an unlimited number of cell divisions. Inhibitors of the enzyme telomerase have been developed to reverse this immortal phenotype and limit the lifespan of cancer cells. Following conventional chemotherapy, these inhibitors could be used to prevent the regrowth of residual disease and reduce the incidence of recurrence. In this chapter, we discuss the development of the first such inhibitor to enter clinical trials, GRN163L. The inhibitor, a lipid-conjugated oligonucleotide developed by Geron Corporation (Menlo Park, CA), inhibits telomerase in a wide range of cancer cell lines. In mice bearing human tumor cells, GRN163L can reduce tumor growth and metastasis. In this chapter, we discuss the development of GRN163L, its mechanism of action, and its potential value in the treatment of cancer patients. In the second half, we discuss anticipated challenges associated with the development of these new drugs, from the search for new compounds to the testing and optimization of current inhibitors.

Original languageEnglish (US)
Title of host publicationPharmaceutical Perspectives of Cancer Therapeutics
PublisherSpringer US
Pages189-205
Number of pages17
ISBN (Print)9781441901309
DOIs
StatePublished - Dec 1 2009

Fingerprint

Telomerase
Cells
Neoplasms
Telomere
Tumors
Bearings (structural)
Therapeutics
Chemotherapy
Telomere Shortening
Enzyme Inhibitors
Chromosomes
Oligonucleotides
Clocks
Cell Division
Action Potentials
Up-Regulation
Lipids
Maintenance
Clinical Trials
Neoplasm Metastasis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Choi, K. H., & Ouellette, M. M. (2009). Role of telomerase in cancer therapeutics. In Pharmaceutical Perspectives of Cancer Therapeutics (pp. 189-205). Springer US. https://doi.org/10.1007/978-1-4419-0131-6_6

Role of telomerase in cancer therapeutics. / Choi, Kyung H.; Ouellette, Michel M.

Pharmaceutical Perspectives of Cancer Therapeutics. Springer US, 2009. p. 189-205.

Research output: Chapter in Book/Report/Conference proceedingChapter

Choi, KH & Ouellette, MM 2009, Role of telomerase in cancer therapeutics. in Pharmaceutical Perspectives of Cancer Therapeutics. Springer US, pp. 189-205. https://doi.org/10.1007/978-1-4419-0131-6_6
Choi KH, Ouellette MM. Role of telomerase in cancer therapeutics. In Pharmaceutical Perspectives of Cancer Therapeutics. Springer US. 2009. p. 189-205 https://doi.org/10.1007/978-1-4419-0131-6_6
Choi, Kyung H. ; Ouellette, Michel M. / Role of telomerase in cancer therapeutics. Pharmaceutical Perspectives of Cancer Therapeutics. Springer US, 2009. pp. 189-205
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