ArticleGenes & development2017
Glioblastoma cellular cross-talk converges on NF-κB to attenuate EGFR inhibitor sensitivity.
Article in Genes & development, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled 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.
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
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Tracing the origins of glioblastoma by investigating the role of gliogenic and related neurogenic genes/signaling pathways in GBM development: a systematic review.World journal of surgical oncology · 2022Pooled it
- Near-infrared photochromic miniprotein enables photoacoustic molecular imaging of acute inflammation and intracellular antigens.Nature methods · 2026Article
- PSMA-Targeted Theranostics in Glioblastoma Multiforme: Current Evidence and Future Perspectives.International journal of molecular sciences · 2026Review
- BRD2 bromodomain-mediated regulation of cell state plasticity modulates therapy response in glioblastoma.Neuro-oncology · 2025Article
- The Pivotal Role of NF-κB in Glioblastoma: Mechanisms of Activation and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Identifying and exploiting combinatorial synthetic lethality by characterizing adaptive kinome rewiring of EGFRvIII-driven glioblastoma.Acta neuropathologica communications · 2025Article
- Effectiveness of PROTAC BET Degraders in Combating Cisplatin Resistance in Head and Neck Cancer Cells.International journal of molecular sciences · 2025Article
- Near-Infrared Photoimmunotherapy in Brain Tumors-An Unexplored Frontier.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Vagus nerve stimulation: Novel concept for the treatment of glioblastoma and solid cancers by cytokine (interleukin-6) reduction, attenuating the SASP, enhancing tumor immunity.Brain, behavior, & immunity - health · 2024Review
- Interleukin 6 and cancer resistance in glioblastoma multiforme.Neurosurgical review · 2024Review
- Targeting drug resistance in glioblastoma (Review).International journal of oncology · 2024Review
- Regulation of Cell Plasticity by Bromodomain and Extraterminal Domain (BET) Proteins: A New Perspective in Glioblastoma Therapy.International journal of molecular sciences · 2023Review
- Review
- FZD1/KLF10-hsa-miR-4762-5p/miR-224-3p-circular RNAs axis as prognostic biomarkers and therapeutic targets for glioblastoma: a comprehensive report.BMC medical genomics · 2023Article
- Regulation of programmed cell death by Brd4.Cell death & disease · 2022Review
- Article
- EGFR, the Lazarus target for precision oncology in glioblastoma.Neuro-oncology · 2022Review
- TERT promoter C228T mutation in neural progenitors confers growth advantage following telomere shortening in vivo.Neuro-oncology · 2022Article
- Phenotypical Flexibility of the EGFRvIII-Positive Glioblastoma Cell Line and the Multidirectional Influence of TGFβ and EGF on These Cells-EGFRvIII Appears as a Weak Oncogene.International journal of molecular sciences · 2022Article
- N6-isopentenyladenosine induces cell death through necroptosis in human glioblastoma cells.Cell death discovery · 2022Article
Corrections and comments
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Authors and funding
28 authors at 6 institutions in 5 countries.
Funding
Abstract
In glioblastoma (GBM), heterogeneous expression of amplified and mutated epidermal growth factor receptor (EGFR) presents a substantial challenge for the effective use of EGFR-directed therapeutics. Here we demonstrate that heterogeneous expression of the wild-type receptor and its constitutively active mutant form, EGFRvIII, limits sensitivity to these therapies through an interclonal communication mechanism mediated by interleukin-6 (IL-6) cytokine secreted from EGFRvIII-positive tumor cells. IL-6 activates a NF-κB signaling axis in a paracrine and autocrine manner, leading to bromodomain protein 4 (BRD4)-dependent expression of the prosurvival protein survivin (BIRC5) and attenuation of sensitivity to EGFR tyrosine kinase inhibitors (TKIs). NF-κB and survivin are coordinately up-regulated in GBM patient tumors, and functional inhibition of either protein or BRD4 in in vitro and in vivo models restores sensitivity to EGFR TKIs. These results provide a rationale for improving anti-EGFR therapeutic efficacy through pharmacological uncoupling of a convergence point of NF-κB-mediated survival that is leveraged by an interclonal circuitry mechanism established by intratumoral mutational heterogeneity.
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What OpenQuestion holds
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.