Telomeres and telomerase: Pharmacological targets for new anticancer strategies?

F. Pendino, I. Tarkanyi, C. Dudognon, J. Hillion, M. Lanotte, J. Aradi, E. Ségal-Bendirdjian

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Telomeres are located at the ends of eukaryotic chromosomes. Human telomerase, a cellular reverse transcriptase, is a ribonucleoprotein enzyme that catalyzes the synthesis and extension of telomeric DNA. It is composed of at least, a template RNA component (hTR; human Telomerase RNA) and a catalytic subunit, the telomerase reverse transcriptase (hTERT). The absence of telomerase is associated with telomere shortening and aging of somatic cells, while high telomerase activity is observed in over 85% of human cancer cells, strongly indicating its key role during tumorigenesis. Several details regarding telomere structure and telomerase regulation have already been elucidated, providing new targets for therapeutic exploitation. Further support for anti-telomerase approaches comes from recent studies indicating that telomerase is endowed of additional functions in the control of growth and survival of tumor cells that do not depend only on the ability of this enzyme to maintain telomere length. This observation suggests that inhibiting telomerase or its synthesis may have additional anti-proliferative and apoptosis inducing effect, independently of the reduction of telomere length during cell divisions. This article reviews the basic information about the biology of telomeres and telomerase and attempts to present various approaches that are currently under investigation to inhibit its expression and its activity. We summarize herein distinct anti-telomerase approaches like antisense strategies, reverse transcriptase inhibitors, and G-quadruplex interacting agents, and also review molecules targeting hTERT expression, such as retinoids and evaluate them for their therapeutic potential.

Original languageEnglish
Pages (from-to)147-180
Number of pages34
JournalCurrent Cancer Drug Targets
Volume6
Issue number2
DOIs
Publication statusPublished - Mar 2006

Fingerprint

Telomerase
Telomere
Pharmacology
G-Quadruplexes
Telomere Shortening
Reverse Transcriptase Inhibitors
Ribonucleoproteins
Cell Aging
RNA-Directed DNA Polymerase
Retinoids
Enzymes
Cell Division
Neoplasms
Cell Survival
Carcinogenesis
Chromosomes
Apoptosis

Keywords

  • Immortalization
  • Senescence
  • Telomerase
  • Telomeres

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Cancer Research

Cite this

Pendino, F., Tarkanyi, I., Dudognon, C., Hillion, J., Lanotte, M., Aradi, J., & Ségal-Bendirdjian, E. (2006). Telomeres and telomerase: Pharmacological targets for new anticancer strategies? Current Cancer Drug Targets, 6(2), 147-180. https://doi.org/10.2174/156800906776056482

Telomeres and telomerase : Pharmacological targets for new anticancer strategies? / Pendino, F.; Tarkanyi, I.; Dudognon, C.; Hillion, J.; Lanotte, M.; Aradi, J.; Ségal-Bendirdjian, E.

In: Current Cancer Drug Targets, Vol. 6, No. 2, 03.2006, p. 147-180.

Research output: Contribution to journalArticle

Pendino, F, Tarkanyi, I, Dudognon, C, Hillion, J, Lanotte, M, Aradi, J & Ségal-Bendirdjian, E 2006, 'Telomeres and telomerase: Pharmacological targets for new anticancer strategies?', Current Cancer Drug Targets, vol. 6, no. 2, pp. 147-180. https://doi.org/10.2174/156800906776056482
Pendino, F. ; Tarkanyi, I. ; Dudognon, C. ; Hillion, J. ; Lanotte, M. ; Aradi, J. ; Ségal-Bendirdjian, E. / Telomeres and telomerase : Pharmacological targets for new anticancer strategies?. In: Current Cancer Drug Targets. 2006 ; Vol. 6, No. 2. pp. 147-180.
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