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
  • [51] Robustness trade-offs and host-microbial symbiosis in the immune system
    Kitano, Hiroaki
    Oda, Kanae
    [J]. MOLECULAR SYSTEMS BIOLOGY, 2006, 2 (1) : 2006.0022
  • [52] EGFR mutation and resistance of non-small-cell lung cancer to gefitinib
    Kobayashi, S
    Boggon, TJ
    Dayaram, T
    Janne, PA
    Kocher, O
    Meyerson, M
    Johnson, BE
    Eck, MJ
    Tenen, DG
    Halmos, B
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (08) : 786 - 792
  • [53] Drug research: myths, hype and reality
    Kubinyi, H
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2003, 2 (08) : 665 - 668
  • [54] THE BYZANTINE GENERALS PROBLEM
    LAMPORT, L
    SHOSTAK, R
    PEASE, M
    [J]. ACM TRANSACTIONS ON PROGRAMMING LANGUAGES AND SYSTEMS, 1982, 4 (03): : 382 - 401
  • [55] POTENTIAL MECHANISM FOR SUSTAINED ANTIRETROVIRAL EFFICACY OF AZT-3TC COMBINATION THERAPY
    LARDER, BA
    KEMP, SD
    HARRIGAN, PR
    [J]. SCIENCE, 1995, 269 (5224) : 696 - 699
  • [56] MULTIPLE MUTATIONS IN HIV-1 REVERSE-TRANSCRIPTASE CONFER HIGH-LEVEL RESISTANCE TO ZIDOVUDINE (AZT)
    LARDER, BA
    KEMP, SD
    [J]. SCIENCE, 1989, 246 (4934) : 1155 - 1158
  • [57] Cancer chronotherapy
    Lévi, F
    [J]. JOURNAL OF PHARMACY AND PHARMACOLOGY, 1999, 51 (08) : 891 - 898
  • [58] Randomised multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer
    Levi, F
    Zidani, R
    Misset, JL
    [J]. LANCET, 1997, 350 (9079) : 681 - 686
  • [59] Circadian chronotherapy for human cancers
    Levi, Francis
    [J]. LANCET ONCOLOGY, 2001, 2 (05) : 307 - 315
  • [60] Zipf's law in importance of genes for cancer classification using microarray data
    Li, WT
    Yang, YN
    [J]. JOURNAL OF THEORETICAL BIOLOGY, 2002, 219 (04) : 539 - 551