ArticleScience signaling2013
Blockade of glioma proliferation through allosteric inhibition of JAK2.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
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.
Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- ODF3B affects the proliferation and apoptosis of glioma via the JAK/STAT pathway.American journal of cancer research · 2024Article
- TRIM32 promotes radioresistance by disrupting TC45-STAT3 interaction in triple-negative breast cancer.Oncogene · 2022Article
- Efficacy of osimertinib plus bevacizumab in glioblastoma patients with simultaneous EGFR amplification and EGFRvIII mutation.Journal of neuro-oncology · 2021Article
- mTOR-Rictor-EGFR axis in oncogenesis and diagnosis of glioblastoma multiforme.Molecular biology reports · 2021Review
- Cinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion.Frontiers in pharmacology · 2021Article
- Discovery of a dual inhibitor of NQO1 and GSTP1 for treating glioblastoma.Journal of hematology & oncology · 2020Article
- Rae1 drives NKG2D binding-dependent tumor development in mice by activating mTOR and STAT3 pathways in tumor cells.Cancer science · 2020Article
- The role of interleukin-6-STAT3 signalling in glioblastoma.Oncology letters · 2018Review
- TRIM59 Promotes Gliomagenesis by Inhibiting TC45 Dephosphorylation of STAT3.Cancer research · 2018Article
- Epidermal growth factor receptor and EGFRvIII in glioblastoma: signaling pathways and targeted therapies.Oncogene · 2018Review
- NQO1 Is Regulated by PTEN in Glioblastoma, Mediating Cell Proliferation and Oxidative Stress.Oxidative medicine and cellular longevity · 2018Article
- Co-amplification of phosphoinositide 3-kinase enhancer A and cyclin-dependent kinase 4 triggers glioblastoma progression.Oncogene · 2017Article
- The critical roles of miR-21 in anti-cancer effects of curcumin.Annals of translational medicine · 2015Review
- Effect of the JAK2/STAT3 inhibitor SAR317461 on human glioblastoma tumorspheres.Journal of translational medicine · 2015Article
- Allosteric targeting of receptor tyrosine kinases.Nature biotechnology · 2014Article
- NF-κB and STAT3 in glioblastoma: therapeutic targets coming of age.Expert review of neurotherapeutics · 2014Review
- The Jak2 small molecule inhibitor, G6, reduces the tumorigenic potential of T98G glioblastoma cells in vitro and in vivo.PloS one · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
The gene that encodes the epidermal growth factor receptor (EGFR) is frequently overexpressed or mutated in human cancers, including glioblastoma. However, the efficacy of EGFR-targeted small-molecule inhibitors or monoclonal antibodies in glioblastomas that also have mutation or deletion of the gene encoding phosphatase and tensin homolog (PTEN) has been modest. We found that EGFR signaling was blocked by a small molecule (G5-7) that selectively inhibited Janus kinase 2 (JAK2)-mediated phosphorylation and activation of EGFR and STAT3 (signal transducer and activator of transcription 3) by binding to JAK2, thereby decreasing the activity of downstream signaling by mTOR (mammalian target of rapamycin) and inducing cell cycle arrest. G5-7 inhibited the proliferation of PTEN-deficient glioblastoma cell lines harboring a constitutively active variant of EGFR (U87MG/EGFRvIII) and human glioblastoma explant neurosphere cultures, but the drug only weakly inhibited the proliferation of either glioblastoma cell lines that were wild type for EGFR and stably transfected with PTEN (U87MG/PTEN) or normal neural progenitor cells and astrocytes. Additionally, G5-7 reduced vascular endothelial growth factor (VEGF) secretion and endothelial cell migration and induced apoptosis in glioblastoma xenografts, thereby suppressing glioblastoma growth in vivo. Furthermore, G5-7 was more potent than EGFR or JAK2 inhibitors that interfere with either ligand or adenosine 5'-triphosphate (ATP) binding at impeding glioblastoma cell proliferation, demonstrating that this allosteric JAK2 inhibitor may be an effective clinical strategy.
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Registered trials
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.