A system perspective on drug response

The effect of drug perturbation(s) is quantified by measuring a specific phenotype. While drug action occurs on a molecular (microscopic) level, the measured phenotypes typically characterise system-level (macroscopic) variables, such as blood pressure or cell viability. Existing drug perturbation models are designed to infer (dosage-dependent) drug effects on the phenotype by analysis of the drug-induced changes in microscopic variables, such as gene expression or metabolite concentration. These changes are used to establish patterns in observed macroscopic variables. Here, we review conventional analysis of drug response and introduce a simple phenomenological description of drug response directly on a macroscopic level. We demonstrate how this approach can be used to establish a framework for quantifying dose-dependent changes in phenotype induced by low concentrations of a single drug or drug combinations. LINKED ARTICLES: This article is part of a themed issue Network Medicine and Systems Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.8/issuetoc.