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dc.contributor.authorNguyen, A
dc.contributor.authorMoussallieh, FM
dc.contributor.authorMackay, A
dc.contributor.authorCicek, AE
dc.contributor.authorCoca, A
dc.contributor.authorChenard, MP
dc.contributor.authorWeingertner, N
dc.contributor.authorLhermitte, B
dc.contributor.authorLetouzé, E
dc.contributor.authorGuérin, E
dc.contributor.authorPencreach, E
dc.contributor.authorJannier, S
dc.contributor.authorGuenot, D
dc.contributor.authorNamer, IJ
dc.contributor.authorJones, C
dc.contributor.authorEntz-Werlé, N
dc.coverage.spatialUnited States
dc.date.accessioned2017-11-22T14:05:20Z
dc.date.issued2017-09-22
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/29069732
dc.identifier16500
dc.identifier.citationOncotarget, 2017, 8 (42), pp. 71597 - 71617
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/930
dc.identifier.eissn1949-2553
dc.identifier.doi10.18632/oncotarget.16500
dc.description.abstractPediatric high grade glioma (pHGGs), including sus-tentorial and diffuse intrinsic pontine gliomas, are known to have a very dismal prognosis. For instance, even an increased knowledge on molecular biology driving this brain tumor entity, there is no treatment able to cure those patients. Therefore, we were focusing on a translational pathway able to increase the cell resistance to treatment and to reprogram metabolically tumor cells, which are, then, adapting easily to a hypoxic microenvironment. To establish, the crucial role of the hypoxic pathways in pHGGs, we, first, assessed their protein and transcriptomic deregulations in a pediatric cohort of pHGGs and in pHGG's cell lines, cultured in both normoxic and hypoxic conditions. Secondly, based on the concept of a bi-therapy targeting in pHGGs mTORC1 (rapamycin) and HIF-1α (irinotecan), we hypothesized that the balanced expressions between RAS/ERK, PI3K/AKT and HIF-1α/HIF-2α/MYC proteins or genes may provide a modulation of the cell response to this double targeting. Finally, we could evidence three protein, genomic and metabolomic profiles of response to rapamycin combined with irinotecan. The pattern of highly sensitive cells to mTOR/HIF-1α targeting was linked to a MYC/ERK/HIF-1α over-expression and the cell resistance to a major hyper-expression of HIF-2α.
dc.format.extent71597 - 71617
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHIF1alpha
dc.subjecthigh grade glioma
dc.subjectmTor
dc.subjectpediatric
dc.subjecttargets
dc.titleCharacterization of the transcriptional and metabolic responses of pediatric high grade gliomas to mTOR-HIF-1α axis inhibition.
dc.typeJournal Article
dcterms.dateAccepted2017-01-16
rioxxterms.versionofrecord10.18632/oncotarget.16500
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-09-22
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfOncotarget
pubs.issue42
pubs.notesNot known
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 Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team
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 Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team
pubs.publication-statusPublished online
pubs.volume8
pubs.embargo.termsNot known
icr.researchteamGlioma Teamen_US
dc.contributor.icrauthorJones, Chris
dc.contributor.icrauthorMackay, Alan


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