ArticleNeuro-oncology2019
Efficacy of EGFR plus TNF inhibition in a preclinical model of temozolomide-resistant glioblastoma.
Article in Neuro-oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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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.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
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- The evolution of chemotherapy in brain tumors: from historical milestones to precision medicine in glioblastoma.Exploration of targeted anti-tumor therapy · 2026Review
- Combination Cancer Therapy and Reference Models for Assessing Drug Synergy in Glioblastoma.Current oncology (Toronto, Ont.) · 2025Review
- STC1-Based Activation of NF-κB Signaling Pathway Induces Epthithelial-Mesenchymal Transition Thus Promotes Progression and Temozolomide Resistance of Glioblastoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Auger electron-emitting EGFR-targeted and non-targeted [EJNMMI radiopharmacy and chemistry · 2025Article
- Application of EGFR-TKIs in brain tumors, a breakthrough in future?Journal of translational medicine · 2025Review
- Cell death in glioblastoma and the central nervous system.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Inflammatory signaling in targeted therapy resistance: focus on EGFR-targeted treatment.Cancer biology & medicine · 2024Article
- EGFR inhibits TNF-α-mediated pathway by phosphorylating TNFR1 at tyrosine 360 and 401.Cell death and differentiation · 2024Article
- Glioblastoma Standard of Care: Effects on Tumor Evolution and Reverse Translation in Preclinical Models.Cancers · 2024Review
- Tumor suppressor role of the complement inhibitor CSMD1 and its role in TNF-induced neuroinflammation in gliomas.Journal of experimental & clinical cancer research : CR · 2024Article
- Review
- EGFR ligand shifts the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastoma by suppressing invasion through BIN3 upregulation.Nature cell biology · 2022Article
- To Explore the Stem Cells Homing to GBM: The Rise to the Occasion.Biomedicines · 2022Review
- Gas Plasma Exposure of Glioblastoma Is Cytotoxic and Immunomodulatory in Patient-Derived GBM Tissue.Cancers · 2022Article
- A Novel TNFSF-Based Signature Predicts the Prognosis and Immunosuppressive Status of Lower-Grade Glioma.BioMed research international · 2022Article
- Comprehensive targeting of resistance to inhibition of RTK signaling pathways by using glucocorticoids.Nature communications · 2021Article
- EGR1 modulated LncRNA HNF1A-AS1 drives glioblastoma progression via miR-22-3p/ENO1 axis.Cell death discovery · 2021Article
- Tumor necrosis factor in lung cancer: Complex roles in biology and resistance to treatment.Neoplasia (New York, N.Y.) · 2021Review
- METTL3 Promotes the Resistance of Glioma to TemozolomideFrontiers in oncology · 2021Article
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundGlioblastoma (GBM) is the most common primary malignant adult brain tumor. Temozolomide (TMZ) is the standard of care and is most effective in GBMs that lack the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). Moreover, even initially responsive tumors develop a secondary resistance to TMZ and become untreatable. Since aberrant epidermal growth factor receptor (EGFR) signaling is widespread in GBM, EGFR inhibition has been tried in multiple clinical trials without success. We recently reported that inhibiting EGFR leads to increased secretion of tumor necrosis factor (TNF) and activation of a survival pathway in GBM. Here, we compare the efficacy of TMZ versus EGFR plus TNF inhibition in an orthotopic mouse model of GBM.
methodsWe use an orthotopic model to examine the efficacy of TMZ versus EGFR plus TNF inhibition in multiple subsets of GBMs, including MGMT methylated and unmethylated primary GBMs, recurrent GBMs, and GBMs rendered experimentally resistant to TMZ.
resultsThe efficacy of the 2 treatments was similar in MGMT methylated GBMs. However, in MGMT unmethylated GBMs, a combination of EGFR plus TNF inhibition was more effective. We demonstrate that the 2 treatment approaches target distinct and non-overlapping pathways. Thus, importantly, EGFR plus TNF inhibition remains effective in TMZ-resistant recurrent GBMs and in GBMs rendered experimentally resistant to TMZ.
conclusionEGFR inhibition combined with a blunting of the accompanying TNF-driven adaptive response could be a viable therapeutic approach in MGMT unmethylated and recurrent EGFR-expressing GBMs.
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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.