title: Systematic synergy modeling: understanding drug synergy from a systems biology perspective.
abstract: Owing to drug synergy effects, drug combinations have become a new trend in combating complex diseases like cancer, HIV and cardiovascular diseases. However, conventional synergy quantification methods often depend on experimental dose-response data which are quite resource-demanding. In addition, these methods are unable to interpret the explicit synergy mechanism. In this review, we give representative examples of how systems biology modeling offers strategies toward better understanding of drug synergy, including the protein-protein interaction (PPI) network-based methods, pathway dynamic simulations, synergy network motif recognitions, integrative drug feature calculations, and "omic"-supported analyses. Although partially successful in drug synergy exploration and interpretation, more efforts should be put on a holistic understanding of drug-disease interactions, considering integrative pharmacology and toxicology factors. With a comprehensive and deep insight into the mechanism of drug synergy, systems biology opens a novel avenue for rational design of effective drug combinations.
authors.affiliation: Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China. di.chen@ia.ac.cn.
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.affiliation: Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China. xi.liu@ia.ac.cn.
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China. yiping.yang@ia.ac.cn.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. hongjun0420@vip.sina.com.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Yang
authors.affiliation: Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China. peng.lu@ia.ac.cn.|Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. peng.lu@ia.ac.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Lu
mesh_terms: D004357:Drug Synergism; D006801:Humans; D008954:Models, Biological; D025941:Protein Interaction Mapping; D049490:Systems Biology / Q000379:methods*