Targeting human telomerase for cancer therapeutics.
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.
Guittat
Lionel
L
Laboratoire de Biophysique, Muséum National d'Histoire Naturelle USM503, INSERM U 565, CNRS UMR 5153, 43, rue Cuvier, 75231, Paris cedex 05, France.
Alberti
Patrizia
P
Gomez
Dennis
D
De Cian
Anne
A
Pennarun
Gaëlle
G
Lemarteleur
Thibault
T
Belmokhtar
Chafke
C
Paterski
Rajaa
R
Morjani
Hamid
H
Trentesaux
Chantal
C
Mandine
Eliane
E
Boussin
François
F
Mailliet
Patrick
P
Lacroix
Laurent
L
Riou
Jean-François
JF
Mergny
Jean-Louis
JL