Evidence map›Paper›PMID 29848664›Full record

ArticleScience translational medicine2018

Ibrutinib inactivates BMX-STAT3 in glioma stem cells to impair malignant growth and radioresistance.

Yu Shi, Olga A Guryanova, Wenchao Zhou, Chong Liu, Zhi Huang, Xiaoguang Fang, Xiuxing Wang, Cong Chen, Qiulian Wu, Zhicheng He and 16 more

Abstract read
In one paragraph

Article in Science translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 1 pooled it
6.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.

  1. Pooled it
  2. Targeting the BMX in cancer: molecular mechanisms and emerging therapeutic strategies.Journal of enzyme inhibition and medicinal chemistry · 2026
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28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors at 6 institutions in 2 countries.

Yu ShiInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China.ORCID 0000-0001-8436-604X
Olga A GuryanovaDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Wenchao ZhouDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.ORCID 0000-0002-6650-1831
Chong LiuDepartment of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Zhi HuangDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Xiaoguang FangDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.ORCID 0000-0002-3368-4133
Xiuxing WangDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, CA 92037, USA.
Cong ChenInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China.
Qiulian WuDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, CA 92037, USA.
Zhicheng HeInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China.
Wei WangDepartment of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Wei ZhangDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Tao JiangDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Qing LiuInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China.
Yaping ChenInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China.
Wenying WangInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China.
Jingjing WuInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China.
Leo KimDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, CA 92037, USA.ORCID 0000-0002-1790-9136
Ryan C GimpleDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, CA 92037, USA.
Hua FengDepartment of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.
Hsiang-Fu KungInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China.
Jennifer S YuDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.ORCID 0000-0002-0244-4014
Jeremy N RichDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, CA 92037, USA.
Yi-Fang PingInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China. baos@ccf.org bianxiuwu@263.net pingyifang@126.com.ORCID 0000-0001-8436-604X
Xiu-Wu BianInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China. baos@ccf.org bianxiuwu@263.net pingyifang@126.com.ORCID 0000-0003-4383-0197
Shideng BaoDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. baos@ccf.org bianxiuwu@263.net pingyifang@126.com.ORCID 0000-0002-4236-2662
Army Medical University · CNCleveland Clinic Lerner College of Medicine · USUniversity of California San Diego · USCapital Medical University · CNCleveland Clinic · USZhejiang University · CN

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
Dynamic Complexity of Brain Tumor Stem Cells (R35CA197718)R35CA197718 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI RICH, JEREMY N · 2015 to 2021
$6.4M
Targeting Ferritin in GlioblastomaR01CA169117 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI BAO, SHIDENG, CONNOR, JAMES ROBERT · 2013 to 2017
$2.7M
Metabolism Informs Intertumoral & Intratumoral HeterogeneityR01NS087913 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NAKANO, ICHIRO, RICH, JEREMY N · 2014 to 2018
$2.0M
Targeting Brain Tumor Stem Cells Through Novel Therapeutic CombinationsR01CA154130 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI RICH, JEREMY N · 2010 to 2014
$1.9M
Functional Inhibition of Deubiquitylase HAUSP to Disrupt Glioblastoma Stem CellsR01CA184090 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI BAO, SHIDENG · 2015 to 2019
$1.8M
Glioblastoma stem cell-derived pericytes and cancer invasionR01NS091080 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI BAO, SHIDENG · 2016 to 2020
$1.7M
Ubiquitination and Deubiquitination of c-Myc in GlioblastomaR01NS099175 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI BAO, SHIDENG · 2016 to 2020
$1.7M
Energy Stress in Brain Tumor Initiating Stem CellsR01NS089272 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RICH, JEREMY N · 2014 to 2018
$1.7M
Instructive Cues in Glioblastoma HierarchiesR01CA171652 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI RICH, JEREMY N · 2014 to 2014
$421k
Epigenetic Regulation of Lipid Metabolism in Glioma Stem CellsF30CA217065 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI GIMPLE, RYAN CHRISTOPHER · 2017 to 2020
$189k
NCI NIH HHS F30 CA217065NCI NIH HHS R01 CA154130NCI NIH HHS R01 CA169117NCI NIH HHS R01 CA171652NCI NIH HHS R01 CA184090NCI NIH HHS R35 CA197718NIGMS NIH HHS T32 GM007250NINDS NIH HHS R01 NS087913NINDS NIH HHS R01 NS089272NINDS NIH HHS R01 NS091080NINDS NIH HHS R01 NS099175
6 · The paper itself

Abstract

Glioblastoma (GBM) is the most lethal primary brain tumor and is highly resistant to current treatments. GBM harbors glioma stem cells (GSCs) that not only initiate and maintain malignant growth but also promote therapeutic resistance including radioresistance. Thus, targeting GSCs is critical for overcoming the resistance to improve GBM treatment. Because the bone marrow and X-linked (BMX) nonreceptor tyrosine kinase is preferentially up-regulated in GSCs relative to nonstem tumor cells and the BMX-mediated activation of the signal transducer and activator of transcription 3 (STAT3) is required for maintaining GSC self-renewal and tumorigenic potential, pharmacological inhibition of BMX may suppress GBM growth and reduce therapeutic resistance. We demonstrate that BMX inhibition by ibrutinib potently disrupts GSCs, suppresses GBM malignant growth, and effectively combines with radiotherapy. Ibrutinib markedly disrupts the BMX-mediated STAT3 activation in GSCs but shows minimal effect on neural progenitor cells (NPCs) lacking BMX expression. Mechanistically, BMX bypasses the suppressor of cytokine signaling 3 (SOCS3)-mediated inhibition of Janus kinase 2 (JAK2), whereas NPCs dampen the JAK2-mediated STAT3 activation via the negative regulation by SOCS3, providing a molecular basis for targeting BMX by ibrutinib to specifically eliminate GSCs while preserving NPCs. Our preclinical data suggest that repurposing ibrutinib for targeting GSCs could effectively control GBM tumor growth both as monotherapy and as adjuvant with conventional therapies.

Indexed as

Radiation ToleranceAdenineAnimalsCell Line, TumorCell ProliferationCombined Modality TherapyCytokine Receptor gp130GliomaJanus Kinase 2MiceModels, BiologicalNeoplastic Stem CellsNeural Stem CellsPiperidinesProtein BindingProtein-Tyrosine KinasesAdenineBMX protein, humanCytokine Receptor gp130ibrutinibJanus Kinase 2PiperidinesProtein-Tyrosine KinasesPyrazolesPyrimidinesSOCS3 protein, humanSTAT3 Transcription FactorSuppressor of Cytokine Signaling 3 ProteinTemozolomide

Identifiers

PMID29848664
PMCPMC6431250
OpenAlexW2805329287

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.