A STAT3-based gene signature stratifies glioma patients for targeted therapy

Melanie Si Yan Tan, Edwin Sandanaraj, Yuk Kien Chong, See Wee Lim, Lynnette Wei Hsien Koh, Wai Hoe Ng, Nguan Soon Tan, Patrick Tan, Beng Ti Ang () and Carol Tang ()
Additional contact information
Melanie Si Yan Tan: National Neuroscience Institute
Edwin Sandanaraj: National Neuroscience Institute
Yuk Kien Chong: National Neuroscience Institute
See Wee Lim: National Neuroscience Institute
Lynnette Wei Hsien Koh: National Neuroscience Institute
Wai Hoe Ng: National Neuroscience Institute
Nguan Soon Tan: Nanyang Technological University
Patrick Tan: Duke-National University of Singapore Medical School
Beng Ti Ang: Agency for Science, Technology and Research (A*STAR)
Carol Tang: National Neuroscience Institute

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-11614-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11614-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-11614-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().