Systems biology approaches for advancing the discovery of effective drug combinations

Journal of Cheminformatics
Karen A Ryall, Aik Choon Tan

Abstract

Complex diseases like cancer are regulated by large, interconnected networks with many pathways affecting cell proliferation, invasion, and drug resistance. However, current cancer therapy predominantly relies on the reductionist approach of one gene-one disease. Combinations of drugs may overcome drug resistance by limiting mutations and induction of escape pathways, but given the enormous number of possible drug combinations, strategies to reduce the search space and prioritize experiments are needed. In this review, we focus on the use of computational modeling, bioinformatics and high-throughput experimental methods for discovery of drug combinations. We highlight cutting-edge systems approaches, including large-scale modeling of cell signaling networks, network motif analysis, statistical association-based models, identifying correlations in gene signatures, functional genomics, and high-throughput combination screens. We also present a list of publicly available data and resources to aid in discovery of drug combinations. Integration of these systems approaches will enable faster discovery and translation of clinically relevant drug combinations. Graphical abstractSpectrum of Systems Biology Approaches for Drug Combinations.

References

Aug 10, 2000·Nature·R AlbertA L Barabasi
Feb 22, 2001·Annual Review of Physiology·J D Molkentin, G W Dorn
Dec 26, 2001·Nucleic Acids Research·Ron EdgarAlex E Lash
Sep 16, 2003·The Journal of Biological Chemistry·Jeffrey J SaucermanAndrew D McCulloch
Mar 3, 2004·Nature Reviews. Cancer·Hiroaki Kitano
Feb 3, 2005·Nature Reviews. Drug Discovery·Curtis T KeithBrent R Stockwell
Feb 19, 2005·Drug Discovery Today·Frank Sams-Dodd
Aug 22, 2006·Nature Chemical Biology·Jonathan B FitzgeraldPeter K Sorger
Aug 29, 2006·Nature Reviews. Molecular Cell Biology·Joerg Heineke, Jeffery D Molkentin
Nov 23, 2006·BMC Neuroscience·Edda Klipp, Wolfram Liebermeister
Feb 6, 2007·Bioinformatics·A FerroD Shasha
Apr 11, 2007·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Matteo Goldoni, Carolina Johansson
May 19, 2007·Nature Reviews. Genetics·Uri Alon
Jun 30, 2007·Nature Reviews. Drug Discovery·Elizabeth IornsAlan Ashworth
May 3, 2008·Cancer Research·I Bernard Weinstein, Andrew Joe
Oct 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ranran ZhangThomas P Loughran
Oct 22, 2008·Nature Chemical Biology·Andrew L Hopkins
Oct 22, 2008·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Hans A KestlerMichael Kühl
Apr 4, 2009·PLoS Computational Biology·Bree B AldridgeDouglas A Lauffenburger
Aug 4, 2009·Bioinformatics·Seth I Berger, Ravi Iyengar
Oct 29, 2009·Carcinogenesis·Pamela K Kreeger, Douglas A Lauffenburger
Dec 25, 2009·Bioinformatics·Yanbin LiuXin Chen
Jan 6, 2010·Circulation·Aldons J Lusis, James N Weiss
Mar 17, 2010·Biochemistry·Melody K MorrisDouglas A Lauffenburger
Mar 20, 2010·Nature Reviews. Cancer·Sreenath V SharmaJeff Settleman
Sep 14, 2010·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Jacob D FealaGiovanni Paternostro
Jun 2, 2011·Nature Reviews. Drug Discovery·Fabio PammolliMassimo Riccaboni
Aug 19, 2011·Science Translational Medicine·Marina SirotaAtul J Butte
Mar 1, 2012·Current Topics in Developmental Biology·Nicolás Peláez, Richard W Carthew
Mar 20, 2012·Cell·Michael S Glickman, Charles L Sawyers

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Citations

Sep 4, 2015·Expert Opinion on Drug Discovery·Violeta I Pérez-Nueno
Dec 17, 2015·Pharmacogenomics·Aik Choon TanPaul H Huang
Mar 17, 2016·Drug Discovery Today·Milla KibbleTero Aittokallio
Sep 15, 2015·Biochemistry·James E LongbothamNigel S Scrutton
Aug 4, 2015·Journal of Cheminformatics·Richard LewisAndreas Bender
Jun 19, 2015·Biochemical and Biophysical Research Communications·Mathurin DorelInna Kuperstein
Apr 6, 2016·Expert Opinion on Drug Discovery·M PennisiF Pappalardo
Nov 3, 2016·Nature Reviews. Clinical Oncology·Juanita S Lopez, Udai Banerji
Sep 3, 2016·BMC Systems Biology·Yu-Ching HsuEric Y Chuang
Oct 27, 2016·CPT: Pharmacometrics & Systems Pharmacology·M K MorrisD A Lauffenburger
Dec 31, 2016·International Journal of Molecular Sciences·Brittany M SalazarShizhen Zhu
Dec 28, 2016·SLAS Technology·Andrea Weiss, Patrycja Nowak-Sliwinska
Jan 18, 2017·Journal of Laboratory Automation·Andrea Weiss, Patrycja Nowak-Sliwinska
Nov 25, 2016·Briefings in Bioinformatics·Seyed Ali Madani TonekaboniBenjamin Haibe-Kains
Dec 15, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hongjie GaoLe Zhang
Mar 3, 2018·Psychopharmacology·Laura B FergusonRoy Dayne Mayfield
Jul 25, 2017·Biochemical Society Transactions·Meichen YuanPu Li
Mar 16, 2019·Pharmaceutics·Tânia F G G CovaSandra C C Nunes
Apr 24, 2019·Critical Reviews in Microbiology·Sinosh SkariyachanBhavya Venkata Krishna
May 27, 2020·Expert Opinion on Drug Discovery·Rajan ChaudhariShuxing Zhang
Sep 23, 2020·Advanced Healthcare Materials·Jason V GregoryJoerg Lahann
Nov 27, 2016·Genome Medicine·Jonathan R DryJulio Saez-Rodriguez
Sep 8, 2018·Frontiers in Oncology·Henry T Marshall, Mustafa B A Djamgoz
Mar 21, 2019·Frontiers in Physiology·Zhihui Wang, Thomas S Deisboeck
May 6, 2017·Briefings in Bioinformatics·Zhen ShengZhiwei Cao
Jan 17, 2017·Journal of Cheminformatics·Muthukumarasamy Karthikeyan, Renu Vyas
Apr 15, 2018·Proceedings of the National Academy of Sciences of the United States of America·Benedict AnchangSylvia K Plevritis
Jun 29, 2018·Bioinformatics·Marinka ZitnikJure Leskovec
May 7, 2019·Journal of Bioinformatics and Computational Biology·Ali CuvitogluZerrin Isik
Nov 24, 2020·ELife·Antonio CappuccioElena Zaslavsky
May 19, 2019·IScience·Chen-Tsung HuangHsueh-Fen Juan
Nov 24, 2018·An International Journal on Information Fusion·Marinka ZitnikMichael M Hoffman
Jun 3, 2021·Pharmaceuticals·Pieter DewulfBernard De Baets
Jul 3, 2021·International Journal of Molecular Sciences·Tapan BehlSimona Gabriela Bungau

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Methods Mentioned

BETA
xenografts

Clinical Trials Mentioned

NCT02188264

Software Mentioned

TIMMA
Netmatch
CMap
Cytoscape
Netflux
CellNOpt
DrugComboRanker
Map

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