Telomerase inhibition in cancer therapeutics: Approaches molecular-based

被引:41
作者
Cunningham, A. P.
Love, W. K.
Zhang, R. W.
Andrews, L. G.
Tollefsbol, T. O.
机构
[1] Univ Alabama Birmingham, Dept Biol, Birmingham, AL 35294 USA
[2] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA
[3] Univ Alabama Birmingham, Ctr Aging, Birmingham, AL 35294 USA
[4] Univ Alabama Birmingham, Ctr AIDS Res, Birmingham, AL 35294 USA
[5] Univ Alabama Birmingham, Gene Therapy Ctr, Birmingham, AL 35294 USA
关键词
telomerase inhibition; hTR; hTERT; antisense; RNAi; ribozyme; dominant-negative hTERT; mutant-template telomerase RNA;
D O I
10.2174/092986706778521887
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Current standard cancer therapies (chemotherapy and radiation) often cause serious adverse off-target effects. Drug design strategies are therefore being developed that will more precisely target cancer cells for destruction while leaving surrounding normal cells relatively unaffected. Telomerase, widely expressed in most human cancers but almost undetectable in normal somatic cells, provides an exciting drug target. This review focuses on recent pharmacogenomic approaches to telomerase inhibition. Antisense oligonucleotides, RNA interference, ribozymes, mutant expression, and the exploitation of differential telomerase expression as a strategy for targeted oncolysis are discussed here in the context of cancer therapeutics. Reports of synergism between telomerase inhibitors and traditional cancer therapeutic agents are also analyzed.
引用
收藏
页码:2875 / 2888
页数:14
相关论文
共 104 条
[31]  
Geary R S, 2001, Curr Opin Investig Drugs, V2, P562
[32]   Telomerase downregulation induced by the G-quadruplex ligand 12459 in A549 cells is mediated by hTERT RNA alternative splicing [J].
Gomez, D ;
Lemarteleur, T ;
Lacroix, L ;
Mailliet, P ;
Mergny, JL ;
Riou, JF .
NUCLEIC ACIDS RESEARCH, 2004, 32 (01) :371-379
[33]   Telomeres [J].
Greider, Carol W. .
CURRENT OPINION IN CELL BIOLOGY, 1991, 3 (03) :444-451
[34]   Telomerase inhibitors - Oligonucleotide phosphoramidates as potential therapeutic agents [J].
Gryaznov, S ;
Pongracz, K ;
Matray, T ;
Schultz, R ;
Pruzan, R ;
Aimi, J ;
Chin, A ;
Harley, C ;
Shea-Herbert, B ;
Shay, J ;
Oshima, Y ;
Asai, A ;
Yamashita, Y .
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, 2001, 20 (4-7) :401-410
[35]   Oligonucleotide N3′ → P5′ thio-phosphoramidate telomerase template antagonists as potential anticancer agents [J].
Gryaznov, S ;
Asai, A ;
Oshima, Y ;
Yamamoto, Y ;
Pongracz, K ;
Pruzan, R ;
Wunder, E ;
Piatyszek, M ;
Li, SH ;
Chin, A ;
Harley, C ;
Akinaga, S ;
Yamashita, Y .
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, 2003, 22 (5-8) :577-581
[36]  
Gu J, 2000, CANCER RES, V60, P5359
[37]   Inhibition of telomerase limits the growth of human cancer cells [J].
Hahn, WC ;
Stewart, SA ;
Brooks, MW ;
York, SG ;
Eaton, E ;
Kurachi, A ;
Beijersbergen, RL ;
Knoll, JHM ;
Meyerson, M ;
Weinberg, RA .
NATURE MEDICINE, 1999, 5 (10) :1164-1170
[38]   TELOMERES SHORTEN DURING AGING OF HUMAN FIBROBLASTS [J].
HARLEY, CB ;
FUTCHER, AB ;
GREIDER, CW .
NATURE, 1990, 345 (6274) :458-460
[39]   TELOMERE LOSS - MITOTIC CLOCK OR GENETIC TIME BOMB [J].
HARLEY, CB .
MUTATION RESEARCH, 1991, 256 (2-6) :271-282
[40]   TELOMERE REDUCTION IN HUMAN COLORECTAL-CARCINOMA AND WITH AGING [J].
HASTIE, ND ;
DEMPSTER, M ;
DUNLOP, MG ;
THOMPSON, AM ;
GREEN, DK ;
ALLSHIRE, RC .
NATURE, 1990, 346 (6287) :866-868