TY - JOUR
T1 - Systems Pharmacology: An opinion on how to turn the impossible into grand challenges.
AU - Westerhoff, H.V.
AU - Nakayama, S.
AU - Mondeel, T.D.
AU - Barberis, M.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
U2 - 10.1016/j.ddtec.2015.06.006
DO - 10.1016/j.ddtec.2015.06.006
M3 - Article
SN - 1740-6749
VL - 15
SP - 23
EP - 31
JO - Drug Discovery Today: Technologies
JF - Drug Discovery Today: Technologies
ER -
