The clinical trials puzzle: How network effects limit drug discovery

被引:2
|
作者
Vasan, Kishore [1 ]
Gysi, Deisy Morselli [1 ,2 ,3 ,4 ]
Barabasi, Albert-Laszlo [1 ,3 ,5 ]
机构
[1] Northeastern Univ, Network Sci Inst, Boston, MA 02115 USA
[2] Univ Fed Parana, Dept Stat, Curtiba, Parana, Brazil
[3] Dept Vet Affairs, Boston, MA 02115 USA
[4] Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Boston, MA USA
[5] Cent European Univ, Dept Data & Network Sci, Budapest, Hungary
关键词
RESEARCH-AND-DEVELOPMENT; PHARMACEUTICAL-INDUSTRY; PREDICTION;
D O I
10.1016/j.isci.2023.108361
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 depth of knowledge offered by post-genomic medicine has carried the promise of new drugs, and cures for multiple diseases. To explore the degree to which this capability has materialized, we extract meta-data from 356,403 clinical trials spanning four decades, aiming to offer mechanistic insights into the innovation practices in drug discovery. We find that convention dominates over innovation, as over 96% of the recorded trials focus on previously tested drug targets, and the tested drugs target only 12% of the human interactome. If current patterns persist, it would take 170 years to target all druggable proteins. We uncover two network-based fundamental mechanisms that currently limit target discovery: preferential attachment, leading to the repeated exploration of previously targeted proteins; and local network effects, limiting exploration to proteins interacting with highly explored proteins. We build on these insights to develop a quantitative network-based model to enhance drug discovery in clinical trials.
引用
收藏
页数:17
相关论文
共 50 条
  • [21] SIDE-EFFECTS AND THE BLINDABILITY OF CLINICAL DRUG TRIALS
    WHITE, K
    KANDO, J
    PARK, T
    WATERNAUX, C
    BROWN, WA
    AMERICAN JOURNAL OF PSYCHIATRY, 1992, 149 (12): : 1730 - 1731
  • [22] Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials
    Xie, Xin
    Yu, Tingting
    Li, Xiang
    Zhang, Nan
    Foster, Leonard J.
    Peng, Cheng
    Huang, Wei
    He, Gu
    SIGNAL TRANSDUCTION AND TARGETED THERAPY, 2023, 8 (01)
  • [23] Zebrafish disease models in drug discovery: from preclinical modelling to clinical trials
    E. Elizabeth Patton
    Leonard I. Zon
    David M. Langenau
    Nature Reviews Drug Discovery, 2021, 20 : 611 - 628
  • [24] Editorial overview: Prion disease: From drug discovery tools to clinical trials
    Chiesa, Roberto
    Vorberg, Ina Maja
    CURRENT OPINION IN PHARMACOLOGY, 2019, 44 : III - V
  • [25] Zebrafish disease models in drug discovery: from preclinical modelling to clinical trials
    Patton, E. Elizabeth
    Zon, Leonard I.
    Langenau, David M.
    NATURE REVIEWS DRUG DISCOVERY, 2021, 20 (08) : 611 - 628
  • [26] Generative artificial intelligence empowers digital twins in drug discovery and clinical trials
    Bordukova, Maria
    Makarov, Nikita
    Rodriguez-Esteban, Raul
    Schmich, Fabian
    Menden, Michael P.
    EXPERT OPINION ON DRUG DISCOVERY, 2024, 19 (01) : 33 - 42
  • [27] Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
    Xin Xie
    Tingting Yu
    Xiang Li
    Nan Zhang
    Leonard J. Foster
    Cheng Peng
    Wei Huang
    Gu He
    Signal Transduction and Targeted Therapy, 8
  • [28] HOW DID THE MALE BECOME THE NORMATIVE STANDARD FOR CLINICAL DRUG TRIALS
    SCOTT, JW
    FOOD AND DRUG LAW JOURNAL, 1993, 48 (02): : 187 - 193
  • [29] Clinical Drug Trials
    Mason, Amy
    PEDIATRICS IN REVIEW, 2018, 39 (03) : 150 - 152
  • [30] The Pharmacogenetics Research Network: From SNP discovery to clinical drug response
    Giacomini, K. M.
    Brett, C. M.
    Altman, R. B.
    Benowitz, N. L.
    Dolan, M. E.
    Flockhart, D. A.
    Johnson, J. A.
    Hayes, D. F.
    Klein, T.
    Krauss, R. M.
    Kroetz, D. L.
    McLeod, H. L.
    Nguyen, A. T.
    Ratain, M. J.
    Relling, M. V.
    Reus, V.
    Roden, D. M.
    Schaefer, C. A.
    Shuldiner, A. R.
    Skaar, T.
    Tantisira, K.
    Tyndale, R. F.
    Wang, L.
    Weinshilboum, R. M.
    Weiss, S. T.
    Zineh, I.
    CLINICAL PHARMACOLOGY & THERAPEUTICS, 2007, 81 (03) : 328 - 345