title: Systems Pharmacology: An opinion on how to turn the impossible into grand challenges.
abstract: A pharmacology that hits single disease-causing molecules with a single drug passively distributing to the target tissue, was almost ready. Such a pharmacology is not (going to be) effective however: a great many diseases are systems biology diseases; complex networks of some hundred thousand types of molecule, determine the functions that constitute human health, through nonlinear interactions. Malfunctions are caused by a variety of molecular failures at the same time; rarely the same variety in different individuals; in complex constellations of OR and AND logics. Few molecules cause disease single-handedly and few drugs will cure the disease all by themselves when dosed for a limited amount of time. We here discuss the implications that this discovery of the network nature of disease should have for pharmacology. We suggest ways in which pharmacokinetics, pharmacodynamics, but also systems biology and genomics may have to change so as better to deal with systems-biology diseases.
authors.affiliation: Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, The Netherlands; Molecular Cell Physiology, Amsterdam Institute for Molecules, Medicines and Systems, VU University Amsterdam, The Netherlands; Manchester Centre for Integrative Systems Biology, The University of Manchester, UK. Electronic address: h.v.westerhoff@uva.nl.
authors.forename: Hans V
authors.initials: HV
authors.lastname: Westerhoff
authors.affiliation: Molecular Cell Physiology, Amsterdam Institute for Molecules, Medicines and Systems, VU University Amsterdam, The Netherlands.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nakayama
authors.affiliation: Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, The Netherlands.
authors.forename: Thierry D G A
authors.initials: TD
authors.lastname: Mondeel
authors.affiliation: Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, The Netherlands.
authors.forename: Matteo
authors.initials: M
authors.lastname: Barberis
mesh_terms: D000818:Animals; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D023281:Genomics / Q000379:methods; D006801:Humans; D008962:Models, Theoretical; D010599:Pharmacokinetics; D010600:Pharmacology; D049490:Systems Biology / Q000379:methods*