Systems Pharmacology: An opinion on how to turn the impossible into grand challenges. (August 2015)

• Record Type: Journal Article
• Authors: Westerhoff, Hans V.; Nakayama, Shintaro; Mondeel, Thierry D.G.A.; Barberis, Matteo
• Is Part Of: Drug discovery today. Volume 15(2015)
• Page Start: 23
• Page End: 31
• Publication Date: 2015-08
• Subjects: Drug development -- Periodicals; Physiology, Pathological -- Periodicals; Drugs -- Design -- Periodicals; 615.1
• DOI: 10.1016/j.ddtec.2015.06.006
• Languages: English
• ISSNs: 1740-6749

Abstract

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.