TY - JOUR
T1 - Systems pharmacology
T2 - Defining the interactions of drug combinations
AU - Coen Van Hasselt, J. G.
AU - Iyengar, Ravi
N1 - Publisher Copyright:
© 2019 by Annual Reviews. All rights reserved.
PY - 2019/1/6
Y1 - 2019/1/6
N2 - The majority of diseases are associated with alterations in multiple molecular pathways and complex interactions at the cellular and organ levels. Single-target monotherapies therefore have intrinsic limitations with respect to their maximum therapeutic benefits. The potential of combination drug therapies has received interest for the treatment of many diseases and is well established in some areas, such as oncology. Combination drug treatments may allow us to identify synergistic drug effects, reduce adverse drug reactions, and address variability in disease characteristics between patients. Identification of combination therapies remains challenging. We discuss current state-of-the-art systems pharmacology approaches to enable rational identification of combination therapies. These approaches, which include characterization of mechanisms of disease and drug action at a systems level, can enable understanding of drug interactions at the molecular, cellular, physiological, and organismal levels. Such multiscale understanding can enable precision medicine by promoting the rational development of combination therapy at the level of individual patients for many diseases.
AB - The majority of diseases are associated with alterations in multiple molecular pathways and complex interactions at the cellular and organ levels. Single-target monotherapies therefore have intrinsic limitations with respect to their maximum therapeutic benefits. The potential of combination drug therapies has received interest for the treatment of many diseases and is well established in some areas, such as oncology. Combination drug treatments may allow us to identify synergistic drug effects, reduce adverse drug reactions, and address variability in disease characteristics between patients. Identification of combination therapies remains challenging. We discuss current state-of-the-art systems pharmacology approaches to enable rational identification of combination therapies. These approaches, which include characterization of mechanisms of disease and drug action at a systems level, can enable understanding of drug interactions at the molecular, cellular, physiological, and organismal levels. Such multiscale understanding can enable precision medicine by promoting the rational development of combination therapy at the level of individual patients for many diseases.
KW - Combination therapy
KW - Modeling
KW - Pharmacodynamics
KW - QSP
KW - Quantitative systems pharmacology
KW - Systems biology
KW - Systems pharmacology
UR - http://www.scopus.com/inward/record.url?scp=85059797285&partnerID=8YFLogxK
U2 - 10.1146/annurev-pharmtox-010818-021511
DO - 10.1146/annurev-pharmtox-010818-021511
M3 - Review article
C2 - 30260737
AN - SCOPUS:85059797285
SN - 0362-1642
VL - 59
SP - 21
EP - 40
JO - Annual Review of Pharmacology and Toxicology
JF - Annual Review of Pharmacology and Toxicology
ER -