ArticleOncogene2012
Acquired MET expression confers resistance to EGFR inhibition in a mouse model of glioblastoma multiforme.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 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
65 citing papers in PubMed, 11 citations in OpenAlex.
- A multicenter, phase II trial of GC1118, a novel anti-EGFR antibody, for recurrent glioblastoma patients with EGFR amplification.Cancer medicine · 2023Trial
- Phase II study of cetuximab in combination with cisplatin and radiation in unresectable, locally advanced head and neck squamous cell carcinoma: Eastern cooperative oncology group trial E3303.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Trial
- Targeting Kinase Signaling in Glioblastoma: Structural Optimization, Blood-Brain Barrier Dynamics and Combinatorial Translational Strategies.International journal of molecular sciences · 2026Review
- Peptides from the Shadows: Molecular Depth Insights and Clinical Horizons of Circular RNA-encoded Peptides in Gliomas.Neuromolecular medicine · 2026Review
- Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Glioblastoma resistance to EGFR antibody-drug conjugate is driven by transcriptional reprogramming and TEK-induced EGFR suppression.Journal of translational medicine · 2025Article
- Heterogeneity of Extracellular Vesicles and Non-Vesicular Nanoparticles in Glioblastoma.Journal of extracellular vesicles · 2025Article
- Signal Amplification for Fluorescent Staining of Single Particles in Liquid Biopsies: Circulating Tumour Cells and Extracellular Vesicles.Journal of extracellular vesicles · 2025Article
- Identifying and exploiting combinatorial synthetic lethality by characterizing adaptive kinome rewiring of EGFRvIII-driven glioblastoma.Acta neuropathologica communications · 2025Article
- Pleiotropic tumor suppressive functions of PTEN missense mutations during gliomagenesis.iScience · 2024Article
- Opportunities and Challenges of Small Molecule Inhibitors in Glioblastoma Treatment: Lessons Learned from Clinical Trials.Cancers · 2024Review
- Lidocaine attenuates TMZ resistance and inhibits cell migration by modulating the MET pathway in glioblastoma cells.Oncology reports · 2024Article
- Driver Mutations Dictate the Immunologic Landscape and Response to Checkpoint Immunotherapy of Glioblastoma.Cancer immunology research · 2023Article
- Personalized Medicine in Brain Gliomas: Targeted Therapy, Patient-Derived Tumor Models (Review).Sovremennye tekhnologii v meditsine · 2023Review
- Machine learning in onco-pharmacogenomics: a path to precision medicine with many challenges.Frontiers in pharmacology · 2023Review
- EGFR, the Lazarus target for precision oncology in glioblastoma.Neuro-oncology · 2022Review
- Variants of the adeno-associated virus serotype 9 with enhanced penetration of the blood-brain barrier in rodents and primates.Nature biomedical engineering · 2022Article
- Review
- Single-cell RNA sequencing reveals evolution of immune landscape during glioblastoma progression.Nature immunology · 2022Article
- Advancements, Challenges, and Future Directions in Tackling Glioblastoma Resistance to Small Kinase Inhibitors.Cancers · 2022Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Glioblastoma multiforme (GBM) is an aggressive brain tumor for which there is no cure. Overexpression of wild-type epidermal growth factor receptor (EGFR) and loss of the tumor suppressor genes Ink4a/Arf and PTEN are salient features of this deadly cancer. Surprisingly, targeted inhibition of EGFR has been clinically disappointing, demonstrating an innate ability for GBM to develop resistance. Efforts at modeling GBM in mice using wild-type EGFR have proven unsuccessful to date, hampering endeavors at understanding molecular mechanisms of therapeutic resistance. Here, we describe a unique genetically engineered mouse model of EGFR-driven gliomagenesis that uses a somatic conditional overexpression and chronic activation of wild-type EGFR in cooperation with deletions in the Ink4a/Arf and PTEN genes in adult brains. Using this model, we establish that chronic activation of wild-type EGFR with a ligand is necessary for generating tumors with histopathological and molecular characteristics of GBMs. We show that these GBMs are resistant to EGFR kinase inhibition and we define this resistance molecularly. Inhibition of EGFR kinase activity using tyrosine kinase inhibitors in GBM tumor cells generates a cytostatic response characterized by a cell cycle arrest, which is accompanied by a substantial change in global gene expression levels. We demonstrate that an important component of this pattern is the transcriptional activation of the MET receptor tyrosine kinase and that pharmacological inhibition of MET overcomes the resistance to EGFR inhibition in these cells. These findings provide important new insights into mechanisms of resistance to EGFR inhibition and suggest that inhibition of multiple targets will be necessary to provide therapeutic benefit for GBM patients.
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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.