ArticleScientific reports2018
Drug treatment efficiency depends on the initial state of activation in nonlinear pathways.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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2 authors at 2 institutions in 1 country.
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Abstract
An accurate prediction of the outcome of a given drug treatment requires quantitative values for all parameters and concentrations involved as well as a detailed characterization of the network of interactions where the target molecule is embedded. Here, we present a high-throughput in silico screening of all potential networks of three interacting nodes to study the effect of the initial conditions of the network in the efficiency of drug inhibition. Our study shows that most network topologies can induce multiple dose-response curves, where the treatment has an enhanced, reduced or even no effect depending on the initial conditions. The type of dual response observed depends on how the potential bistable regimes interplay with the inhibition of one of the nodes inside a nonlinear pathway architecture. We propose that this dependence of the strength of the drug on the initial state of activation of the pathway may be affecting the outcome and the reproducibility of drug studies and clinical trials.
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