Integrating genetic approaches into the discovery of anticancer drugs

被引:592
作者
Hartwell, LH
Szankasi, P
Roberts, CJ
Murray, AW
Friend, SH
机构
[1] FRED HUTCHINSON CANC RES CTR, DEPT MOL PHARMACOL, SEATTLE PROJECT, SEATTLE, WA 98109 USA
[2] ROSETTA INPHARMAT INC, KIRKLAND, WA 98034 USA
[3] UNIV CALIF SAN FRANCISCO, DEPT PHYSIOL, SAN FRANCISCO, CA 94142 USA
关键词
D O I
10.1126/science.278.5340.1064
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The discovery of anticancer drugs is now driven by the numerous molecular alterations identified in tumor cells over the past decade. To exploit these alterations, it is necessary to understand how they define a molecular context that allows increased sensitivity to particular compounds. Traditional genetic approaches together with the new wealth of genomic information for both human and model organisms open up strategies by which drugs can be profiled for their ability to selectively kill cells in a molecular context that matches those found in tumors. Similarly, it may be possible to identify and validate new targets for drugs that would selectively kill tumor cells with a particular molecular context. This article outlines some of the ways that yeast genetics can be used to streamline anticancer drug discovery.
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页码:1064 / 1068
页数:5
相关论文
共 74 条
  • [1] Antisense oligonucleotides: Towards clinical trials
    Agrawal, S
    [J]. TRENDS IN BIOTECHNOLOGY, 1996, 14 (10) : 376 - 387
  • [2] THE NF1 LOCUS ENCODES A PROTEIN FUNCTIONALLY RELATED TO MAMMALIAN GAP AND YEAST IRA PROTEINS
    BALLESTER, R
    MARCHUK, D
    BOGUSKI, M
    SAULINO, A
    LETCHER, R
    WIGLER, M
    COLLINS, F
    [J]. CELL, 1990, 63 (04) : 851 - 859
  • [3] Reduced X-ray resistance and homologous recombination frequencies in a RAD54(-/-) mutant of the chicken DT40 cell line
    Bezzubova, O
    Silbergleit, A
    YamaguchiIwai, Y
    Takeda, S
    Buerstedde, JM
    [J]. CELL, 1997, 89 (02) : 185 - 193
  • [4] Ras-regulated signaling processes in Saccharomyces cerevisiae
    Broach, James R.
    [J]. CURRENT OPINION IN GENETICS & DEVELOPMENT, 1991, 1 (03) : 370 - 377
  • [5] Double indemnity: p53, BRCA and cancer
    Brugarolas, J
    Jacks, T
    [J]. NATURE MEDICINE, 1997, 3 (07) : 721 - 722
  • [6] Control of cell cycle arrest by the Mec1(sc)/Rad3(sp) DNA structure checkpoint pathway
    Carr, AM
    [J]. CURRENT OPINION IN GENETICS & DEVELOPMENT, 1997, 7 (01) : 93 - 98
  • [7] Decreased levels of the cell-cycle inhibitor p27(Kip1) protein: Prognostic implications in primary breast cancer
    Catzavelos, C
    Bhatacharya, N
    Ung, YC
    Wilson, JA
    Roncari, L
    Sandhu, C
    Shaw, P
    Yeger, H
    MoravaProtzner, I
    Kapusta, L
    Franssen, E
    Pritchard, KI
    Slingerland, JM
    [J]. NATURE MEDICINE, 1997, 3 (02) : 227 - 230
  • [8] CHEN JM, 1992, CARCINOGENESIS, V13, P1503
  • [9] COMIS RL, 1994, SEMIN ONCOL, V21, P109
  • [10] Anti-gene therapy: The use of ribozymes to inhibit gene function
    Couture, LA
    Stinchcomb, DT
    [J]. TRENDS IN GENETICS, 1996, 12 (12) : 510 - 515