Telomere maintenance mechanisms as a target for drug development

被引:62
作者
Bearss, DJ
Hurley, LH
Von Hoff, DD
机构
[1] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA
[2] Univ Arizona, Coll Pharm, Tucson, AZ 85724 USA
关键词
telomere; telomerase; G-quadruplex; drug targets;
D O I
10.1038/sj.onc.1204092
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
The shortening of the telomeric DNA sequences at the ends of chromosomes is thought to play a critical role in regulating the lifespan of human cells. Since all dividing cells are subject to the loss of telomeric sequences, cells with long proliferative lifespans need mechanisms to maintain telomere integrity. It appears that the activation of the enzyme telomerase is the major mechanism by which these cells maintain their telomeres, The proposal that a critical step in the process of the malignant transformation of cells is the upregulation of expression of telomerase has made this enzyme a potentially useful prognostic and diagnostic marker for cancer, as well as a new target for therapeutic intervention for the treatment of patients with cancer, It is now clear that simply inhibiting telomerase may not result in the anticancer effects that were originally hypothesized. While telomerase may not be the universal target for cancer therapy, we certainly believe that targeting the telomere maintenance mechanisms will be important in future research aimed toward a successful strategy for curing cancer.
引用
收藏
页码:6632 / 6641
页数:10
相关论文
共 123 条
  • [1] SIGNIFICANT TELOMERE SHORTENING IN CHILDHOOD LEUKEMIA
    ADAMSON, DJA
    KING, DJ
    HAITES, NE
    [J]. CANCER GENETICS AND CYTOGENETICS, 1992, 61 (02) : 204 - 206
  • [2] ANTHRACENE-9,10-DIONES AS POTENTIAL ANTICANCER AGENTS - SYNTHESIS, DNA-BINDING, AND BIOLOGICAL STUDIES ON A SERIES OF 2,6-DISUBSTITUTED DERIVATIVES
    AGBANDJE, M
    JENKINS, TC
    MCKENNA, R
    RESZKA, AP
    NEIDLE, S
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (08) : 1418 - 1429
  • [3] HUMAN TELOMERES CONTAIN AT LEAST 3 TYPES OF G-RICH REPEAT DISTRIBUTED NON-RANDOMLY
    ALLSHIRE, RC
    DEMPSTER, M
    HASTIE, ND
    [J]. NUCLEIC ACIDS RESEARCH, 1989, 17 (12) : 4611 - 4627
  • [4] TELOMERE LENGTH PREDICTS REPLICATIVE CAPACITY OF HUMAN FIBROBLASTS
    ALLSOPP, RC
    VAZIRI, H
    PATTERSON, C
    GOLDSTEIN, S
    YOUNGLAI, EV
    FUTCHER, AB
    GREIDER, CW
    HARLEY, CB
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (21) : 10114 - 10118
  • [5] PARP-2, a novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase
    Amé, JC
    Rolli, V
    Schreiber, V
    Niedergang, C
    Apiou, F
    Decker, P
    Muller, S
    Hoger, T
    Murcia, JMD
    de Murcia, G
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (25) : 17860 - 17868
  • [6] Porphyrin binding to quadruplexed T4G4
    Anantha, NV
    Azam, M
    Sheardy, RD
    [J]. BIOCHEMISTRY, 1998, 37 (09) : 2709 - 2714
  • [7] Bare LA, 1998, DRUG DEVELOP RES, V43, P109, DOI 10.1002/(SICI)1098-2299(199802)43:2<109::AID-DDR4>3.0.CO
  • [8] 2-O
  • [9] Reconstitution of human telomerase activity in vitro
    Beattie, TL
    Zhou, W
    Robinson, MO
    Harrington, L
    [J]. CURRENT BIOLOGY, 1998, 8 (03) : 177 - 180
  • [10] A NUCLEIC-ACID TRIPLE-HELIX FORMED BY A PEPTIDE NUCLEIC-ACID DNA COMPLEX
    BETTS, L
    JOSEY, JA
    VEAL, JM
    JORDAN, SR
    [J]. SCIENCE, 1995, 270 (5243) : 1838 - 1841