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. 2004 Jun;45(1-2):75–90. doi: 10.1007/s10616-004-5127-z

Targeting human telomerase for cancer therapeutics

Lionel Guittat 1, Patrizia Alberti 1, Dennis Gomez 2, Anne De Cian 1, Gaëlle Pennarun 1,3, Thibault Lemarteleur 2, Chafke Belmokhtar 4, Rajaa Paterski 2, Hamid Morjani 2, Chantal Trentesaux 2, Eliane Mandine 4, François Boussin 3, Patrick Mailliet 4, Laurent Lacroix 1, Jean-François Riou 2, Jean-Louis Mergny 1,✉
PMCID: PMC3449961  PMID: 19003245

Abstract

The enzyme telomerase is involved in the replication of telomeres, specialized structures that cap and protect the ends of chromosomes. Its activity is required for maintenance of telomeres and for unlimited lifespan, a hallmark of cancer cells. Telomerase is overexpressed in the vast majority of human cancer cells and therefore represents an attractive target for therapy. Several approaches have been developed to inhibit this enzyme through the targeting of its RNA or catalytic components as well as its DNA substrate, the single-stranded 3′-telomeric overhang. Telomerase inhibitors are chemically diverse and include modified oligonucleotides as well as small diffusable molecules, both natural and synthetic. This review presents an update of recent investigations pertaining to these agents and discusses their biological properties in the context of the initial paradigm that the exposure of cancer cells to these agents should lead to progressive telomere shortening followed by a delayed growth arrest response.

Keywords: Apoptosis, Cancer, G-quadruplex ligands, G-quartets, Senescence, Telomerase, Telomere

Full Text

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Glossary

2′MOE

2′-O-(2-methoxyethyl) RNA

2′OMe

2′-O-methyl-RNA

hTERT

human Telomerase Reverse Transcriptase

hTR

human Telomerase RNA

LNA

locked nucleic acids

PN

phosphoramidate

PNA

peptide nucleic acids

PS

phosphorothioate

TRAP

Telomeric Repeat Amplification Protocol

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