Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-019-11614-x
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dc.titleA STAT3-based gene signature stratifies glioma patients for targeted therapy
dc.contributor.authorTan, M.S.Y.
dc.contributor.authorSandanaraj, E.
dc.contributor.authorChong, Y.K.
dc.contributor.authorLim, S.W.
dc.contributor.authorKoh, L.W.H.
dc.contributor.authorNg, W.H.
dc.contributor.authorTan, N.S.
dc.contributor.authorTan, P.
dc.contributor.authorAng, B.T.
dc.contributor.authorTang, C.
dc.date.accessioned2021-11-16T03:35:25Z
dc.date.available2021-11-16T03:35:25Z
dc.date.issued2019
dc.identifier.citationTan, M.S.Y., Sandanaraj, E., Chong, Y.K., Lim, S.W., Koh, L.W.H., Ng, W.H., Tan, N.S., Tan, P., Ang, B.T., Tang, C. (2019). A STAT3-based gene signature stratifies glioma patients for targeted therapy. Nature Communications 10 (1) : 3601. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-019-11614-x
dc.identifier.issn2041-1723
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/206242
dc.description.abstractIntratumoral heterogeneity is a hallmark of glioblastoma (GBM) tumors, thought to negatively influence therapeutic outcome. Previous studies showed that mesenchymal tumors have a worse outcome than the proneural subtype. Here we focus on STAT3 as its activation precedes the proneural-mesenchymal transition. We first establish a STAT3 gene signature that stratifies GBM patients into STAT3-high and -low cohorts. STAT3 inhibitor treatment selectively mitigates STAT3-high cell viability and tumorigenicity in orthotopic mouse xenograft models. We show the mechanism underlying resistance in STAT3-low cells by combining STAT3 signature analysis with kinome screen data on STAT3 inhibitor-treated cells. This allows us to draw connections between kinases affected by STAT3 inhibitors, their associated transcription factors and target genes. We demonstrate that dual inhibition of IGF-1R and STAT3 sensitizes STAT3-low cells and improves survival in mice. Our study underscores the importance of serially profiling tumors so as to accurately target individuals who may demonstrate molecular subtype switching. © 2019, The Author(s).
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceScopus OA2019
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1038/s41467-019-11614-x
dc.description.sourcetitleNature Communications
dc.description.volume10
dc.description.issue1
dc.description.page3601
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