Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-019-11614-x
Title: A STAT3-based gene signature stratifies glioma patients for targeted therapy
Authors: Tan, 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. 
Issue Date: 2019
Publisher: Nature Publishing Group
Citation: Tan, 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
Rights: Attribution 4.0 International
Abstract: Intratumoral 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).
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/206242
ISSN: 2041-1723
DOI: 10.1038/s41467-019-11614-x
Rights: Attribution 4.0 International
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