ArticleNature neuroscience2017
A TNF-JNK-Axl-ERK signaling axis mediates primary resistance to EGFR inhibition in glioblastoma.
Article in Nature neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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
83 citing papers in PubMed, 111 citations in OpenAlex.
- AXL at the nexus of therapeutic resistance, tumor vascularization, and immune evasion in cancer.iScience · 2026Review
- Inhibition of AXL receptor tyrosine kinase increases osteoblast function and bone mass.Bone research · 2026Article
- Interleukin-1α-Mediated Activation of TNF-α/NF-κB Signaling Confers Resistance to Osimertinib in EGFR-Mutant Non-Small-Cell Lung Cancer.Thoracic cancer · 2026Article
- Modeling blood-brain barrier-glioblastoma interactions: implications for chemoresistance and therapeutic targeting.Fluids and barriers of the CNS · 2026Review
- An EGFR co-amplified lncRNA HELDR promotes glioblastoma malignancy through KAT7-driven gene programs.Nature cell biology · 2026Article
- Diffuse Midline Gliomas: Clinical, Diagnostic, and Therapeutic Perspectives.Biomedicines · 2026Review
- Dysregulation of post-translational modifications in glioma: advances in pathological mechanisms and clinical targeting strategies.Journal of translational medicine · 2026Review
- Drug resistance in glioblastoma: Challenges, mechanisms and therapeutic strategies (Review).Molecular and clinical oncology · 2026Review
- Periostin Safeguards EGFR-Driven Genomic Instability and Sustains the Immune-Suppressive Niche in Glioblastoma.Human mutation · 2026Article
- Combination Cancer Therapy and Reference Models for Assessing Drug Synergy in Glioblastoma.Current oncology (Toronto, Ont.) · 2025Review
- Review
- CD24 is a promising immunotherapeutic target for enhancing efficacy of third-generation EGFR-TKIs on EGFR-mutated lung cancer.Cancer communications (London, England) · 2025Article
- Understanding and overcoming multidrug resistance in cancer.Nature reviews. Clinical oncology · 2025Review
- Article
- Copper's new role in cancer: how cuproptosis-related genes could revolutionize glioma treatment.BMC cancer · 2025Article
- Targeting rapid TKI-induced AXL upregulation overcomes adaptive ERK reactivation and exerts antileukemic effects in FLT3/ITD acute myeloid leukemia.Molecular oncology · 2025Article
- It's all downstream from here: RTK/Raf/MEK/ERK pathway resistance mechanisms in glioblastoma.Journal of neuro-oncology · 2025Review
- Cell death in glioblastoma and the central nervous system.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Multicellular Network-Informed Survival Model for Identification of Drug Targets of Gliomas.IEEE journal of biomedical and health informatics · 2025Article
- LAMB1 downregulation suppresses glioma progression by inhibiting aerobic glycolysis through regulation of the NF-κB/HK2 axis.Discover oncology · 2025Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Aberrant epidermal growth factor receptor (EGFR) signaling is widespread in cancer, making the EGFR an important target for therapy. EGFR gene amplification and mutation are common in glioblastoma (GBM), but EGFR inhibition has not been effective in treating this tumor. Here we propose that primary resistance to EGFR inhibition in glioma cells results from a rapid compensatory response to EGFR inhibition that mediates cell survival. We show that in glioma cells expressing either EGFR wild type or the mutant EGFRvIII, EGFR inhibition triggers a rapid adaptive response driven by increased tumor necrosis factor (TNF) secretion, which leads to activation in turn of c-Jun N-terminal kinase (JNK), the Axl receptor tyrosine kinase and extracellular signal-regulated kinases (ERK). Inhibition of this adaptive axis at multiple nodes rendered glioma cells with primary resistance sensitive to EGFR inhibition. Our findings provide a possible explanation for the failures of anti-EGFR therapy in GBM and suggest a new approach to the treatment of EGFR-expressing GBM using a combination of EGFR and TNF inhibition.
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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.