Drug treatment efficiency depends on the initial state of activation in nonlinear pathways

Doldan Martelli, Victoria Lucia; Miguez, David G

Publication:
Drug treatment efficiency depends on the initial state of activation in nonlinear pathways

dc.affiliation.dpto	UC3M. Departamento de Matemáticas	es
dc.affiliation.grupoinv	UC3M. Grupo de Investigación: Interdisciplinar de Sistemas Complejos (GISC)	es
dc.contributor.author	Doldan Martelli, Victoria Lucia
dc.contributor.author	Miguez, David G
dc.contributor.funder	Ministerio de Economía y Competitividad (España)	es
dc.date.accessioned	2019-07-12T09:02:40Z
dc.date.available	2019-07-12T09:02:40Z
dc.date.issued	2018-08-21
dc.description.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.	es
dc.description.sponsorship	This work has been supported by the Ministry of Science and Technology of Spain via a Ramón y Cajal Fellowship (Ref. RYC-2010-07450), a grant from Plan Nacional framework (Ref. BFU2011-30303 and & BFU2014-53299-P) and a FPU fellowship. We thank Raúl Guantes, Juan Díaz Colunga, Marta Ibañes, Rosa Martínez Corral, Saúl Ares and Katherine Gonzales for invaluable help and technical assistance.	es
dc.format.extent	10	es
dc.identifier.bibliographicCitation	Doldán-Martelli, V. y Míguez, D. G. (2018). Drug treatment efficiency depends on the initial state of activation in nonlinear pathways. Scientific Reports, 8, 12495.	es
dc.identifier.doi	10.1038/s41598-018-30913-9
dc.identifier.issn	2045-2322
dc.identifier.publicationtitle	Scientific Reports	es
dc.identifier.publicationvolume	8	es
dc.identifier.uri	https://hdl.handle.net/10016/28583
dc.identifier.uxxi	AR/0000022158
dc.language.iso	eng	es
dc.publisher	Nature Research	es
dc.relation.projectID	Gobierno de España. RYC-2010-07450	es
dc.relation.projectID	Gobierno de España. BFU2011-30303	es
dc.relation.projectID	Gobierno de España. BFU2014-53299-P	es
dc.rights	© The Author(s) 2018.	es
dc.rights	Atribución 3.0 España	*
dc.rights.accessRights	open access	es
dc.rights.uri	http://creativecommons.org/licenses/by/3.0/es/	*
dc.subject.eciencia	Matemáticas	es
dc.title	Drug treatment efficiency depends on the initial state of activation in nonlinear pathways	es
dc.type	research article	*
dc.type.hasVersion	VoR	*
dspace.entity.type	Publication