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dc.contributor.authorMurillo, MMen_US
dc.contributor.authorRana, Sen_US
dc.contributor.authorSpencer-Dene, Ben_US
dc.contributor.authorNye, Een_US
dc.contributor.authorStamp, Gen_US
dc.contributor.authorDownward, Jen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2019-02-20T07:40:43Z
dc.date.issued2018-12-26en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30590030en_US
dc.identifierS2211-1247(18)31914-4en_US
dc.identifier.citationCell Rep, 2018, 25 (13), pp. 3545 - 3553.e2en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3056
dc.identifier.eissn2211-1247en_US
dc.identifier.doi10.1016/j.celrep.2018.12.003en_US
dc.description.abstractRAS family GTPases contribute directly to the regulation of type I phosphoinositide 3-kinases (PI3Ks) via RAS-binding domains in the PI3K catalytic p110 subunits. Disruption of this domain of p110α impairs RAS-mutant-oncogene-driven tumor formation and maintenance. Here, we test the effect of blocking the interaction of RAS with p110α on epidermal growth factor receptor (EGFR)-mutant-driven lung tumorigenesis. Disrupting the RAS-PI3K interaction inhibits activation of both AKT and RAC1 in EGFR-mutant lung cancer cells, leading to reduced growth and survival, and inhibits EGFR-mutant-induced tumor onset and promotes major regression of established tumors in an autochthonous mouse model of EGFR-mutant-induced lung adenocarcinoma. The RAS-PI3K interaction is thus an important signaling node and potential therapeutic target in EGFR-mutant lung cancer, even though RAS oncogenes are not themselves mutated in this setting, suggesting different strategies for tackling tyrosine kinase inhibitor resistance in lung cancer.en_US
dc.format.extent3545 - 3553.e2en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectEGFRen_US
dc.subjectKRASen_US
dc.subjectPI3Ken_US
dc.subjectPIK3CAen_US
dc.subjectRAC1en_US
dc.subjectRASen_US
dc.subjectlung canceren_US
dc.titleDisruption of the Interaction of RAS with PI 3-Kinase Induces Regression of EGFR-Mutant-Driven Lung Cancer.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-11-30en_US
rioxxterms.versionofrecord10.1016/j.celrep.2018.12.003en_US
rioxxterms.licenseref.startdate2018-12-26en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfCell Repen_US
pubs.issue13en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Lung Cancer Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Experimental Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Lung Cancer Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume25en_US
pubs.embargo.termsNot knownen_US
icr.researchteamExperimental Pathologyen_US
icr.researchteamLung Cancer Groupen_US
dc.contributor.icrauthorStamp, Gordonen_US
dc.contributor.icrauthorDownward, Julian David Harryen_US


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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/