Innovation - A robustness-based approach to systems-oriented drug design

被引:350
作者
Kitano, Hiroaki [1 ]
机构
[1] Sony Comp Sci Labs Inc, Shinagawa Ku, Tokyo 1410022, Japan
[2] Syst Biol Inst, Tokyo 1500001, Japan
[3] Inst Canc Res, Dept Canc Syst Biol, Koutou Ku, Tokyo 1358550, Japan
基金
日本科学技术振兴机构;
关键词
D O I
10.1038/nrd2195
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Many potential drugs that specifically target a particular protein considered to underlie a given disease have been found to be less effective than hoped, or to cause significant side effects. The intrinsic robustness of living systems against various perturbations is a key factor that prevents such compounds from being successful. By studying complex network systems and reformulating control and communication theories that are well established in engineering, a theoretical foundation for a systems-oriented approach to more effectively control the robustness of living systems, particularly at the cellular level, could be developed. Here, I use examples that are based on existing drugs to illustrate the concept of robustness, and then discuss how a greater consideration of the importance of robustness could influence the design of new drugs that will be intended to control complex systems.
引用
收藏
页码:202 / 210
页数:9
相关论文
共 102 条
  • [61] Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin)
    Lu, YH
    Zi, XL
    Zhao, YH
    Mascarenhas, D
    Pollak, M
    [J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2001, 93 (24): : 1852 - 1857
  • [62] TYROSINE KINASE-ACTIVITY AND TRANSFORMATION POTENCY OF BCR-ABL ONCOGENE PRODUCTS
    LUGO, TG
    PENDERGAST, AM
    MULLER, AJ
    WITTE, ON
    [J]. SCIENCE, 1990, 247 (4946) : 1079 - 1082
  • [63] Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib
    Lynch, TJ
    Bell, DW
    Sordella, R
    Gurubhagavatula, S
    Okimoto, RA
    Brannigan, BW
    Harris, PL
    Haserlat, SM
    Supko, JG
    Haluska, FG
    Louis, DN
    Christiani, DC
    Settleman, J
    Haber, DA
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (21) : 2129 - 2139
  • [64] Decomposition of metabolic network into functional modules based on the global connectivity structure of reaction graph
    Ma, HW
    Zhao, XM
    Yuan, YJ
    Zeng, AP
    [J]. BIOINFORMATICS, 2004, 20 (12) : 1870 - 1876
  • [65] Mendel DB, 2003, CLIN CANCER RES, V9, P327
  • [66] In vivo robustness analysis of cell division cycle genes in Saccharomyces cerevisiae
    Moriya, Hisao
    Shimizu-Yoshida, Yuki
    Kitano, Hiroaki
    [J]. PLOS GENETICS, 2006, 2 (07): : 1034 - 1045
  • [67] Mormont MC, 1997, INT J CANCER, V70, P241, DOI 10.1002/(SICI)1097-0215(19970117)70:2<241::AID-IJC16>3.0.CO
  • [68] 2-L
  • [69] Motwani M, 2001, CLIN CANCER RES, V7, P4209
  • [70] Nagata Y, 2004, CANCER CELL, V6, P117, DOI 10.1016/j.ccr.2004.06.022