Drug Target Optimization in Chronic Myeloid Leukemia Using Innovative Computational Platform

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dc.citation.journalTitleScientific Reportsen_US
dc.citation.volumeNumber5en_US
dc.contributor.authorChuang, Ryanen_US
dc.contributor.authorHall, Benjamin A.en_US
dc.contributor.authorBenque, Daviden_US
dc.contributor.authorCook, Byronen_US
dc.contributor.authorIshtiaq, Saminen_US
dc.contributor.authorPiterman, Niren_US
dc.contributor.authorTaylor, Alexen_US
dc.contributor.authorVardi, Mosheen_US
dc.contributor.authorKoschmieder, Steffenen_US
dc.contributor.authorGottgens, Bertholden_US
dc.contributor.authorFisher, Jasminen_US
dc.date.accessioned2015-05-15T17:06:34Zen_US
dc.date.available2015-05-15T17:06:34Zen_US
dc.date.issued2015en_US
dc.description.abstractChronic Myeloid Leukemia (CML) represents a paradigm for the wider cancer field. Despite the fact that tyrosine kinase inhibitors have established targeted molecular therapy in CML, patients often face the risk of developing drug resistance, caused by mutations and/or activation of alternative cellular pathways. To optimize drug development, one needs to systematically test all possible combinations of drug targets within the genetic network that regulates the disease. The BioModelAnalyzer (BMA) is a user-friendly computational tool that allows us to do exactly that. We used BMA to build a CML network-model composed of 54 nodes linked by 104 interactions that encapsulates experimental data collected from 160 publications. While previous studies were limited by their focus on a single pathway or cellular process, our executable model allowed us to probe dynamic interactions between multiple pathways and cellular outcomes, suggest new combinatorial therapeutic targets, and highlight previously unexplored sensitivities to Interleukin-3.en_US
dc.identifier.citationChuang, Ryan, Hall, Benjamin A., Benque, David, et al.. "Drug Target Optimization in Chronic Myeloid Leukemia Using Innovative Computational Platform." <i>Scientific Reports,</i> 5, (2015) Nature Publishing Group: http://dx.doi.org/10.1038/srep08190.en_US
dc.identifier.doihttp://dx.doi.org/10.1038/srep08190en_US
dc.identifier.urihttps://hdl.handle.net/1911/80223en_US
dc.language.isoengen_US
dc.publisherNature Publishing Groupen_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.subject.keywordcomputer modellingen_US
dc.subject.keyworddrug developmenten_US
dc.titleDrug Target Optimization in Chronic Myeloid Leukemia Using Innovative Computational Platformen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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