ArticleCancer discovery2012
Differential sensitivity of glioma- versus lung cancer-specific EGFR mutations to EGFR kinase inhibitors.
Article in Cancer discovery, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 224 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
224 citing papers in PubMed, 1 synthesis or guideline pooled it, 338 citations in OpenAlex.
- Knockdown of Tousled‑like kinase 1 inhibits survival of glioblastoma multiforme cells.International journal of molecular medicine · 2020Pooled it
- Effect of lapatinib on meningioma growth in adults with neurofibromatosis type 2.Journal of neuro-oncology · 2018Trial
- Report of safety of pulse dosing of lapatinib with temozolomide and radiation therapy for newly-diagnosed glioblastoma in a pilot phase II study.Journal of neuro-oncology · 2017Trial
- Phase I/randomized phase II study of afatinib, an irreversible ErbB family blocker, with or without protracted temozolomide in adults with recurrent glioblastoma.Neuro-oncology · 2015Trial
- Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: North American Brain Tumor Consortium trial 04-02.Neuro-oncology · 2014Trial
- Exploring the landscape of targetable alterations in patients with glioblastoma.Nature reviews. Clinical oncology · 2026Review
- Integrative bioinformatics analysis of Lianmei granules in diabetic nephropathy: Epidemiological and molecular insights.Medicine · 2026Article
- Review
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- Review
- Ethical considerations in randomization for neurosurgical oncology trials: A scoping review.Neuro-oncology practice · 2026Review
- An alternative EGFR activation by patient-derived R252C mutation promotes cancer progression.Nature communications · 2026Article
- Case Report: Epidermal growth factor receptor germline variant associated with epilepsy and rare, distinctive cerebral MRI abnormalities.Frontiers in radiology · 2026Article
- Genomic characterization of rabies virus glycoprotein co-expressing CD70 CAR-T cells during killing of glioma cellsFrontiers in immunology · 2026Article
- Glioma drug development benefits from emerging phase 0 and window-of-opportunity trial paradigm.Cell communication and signaling : CCS · 2025Review
- Oncogene-driven lung cancer in the era of radiogenomics: current evidence and future developments.Discover oncology · 2025Review
- Redox-Regulated Pathways in Glioblastoma Stem-like Cells: Mechanistic Insights and Therapeutic Implications.Brain sciences · 2025Review
- CNS Tumor with BCOR/BCORL1 Fusion: A Rare Tumor Entity.International journal of molecular sciences · 2025Article
- Key genes altered in glioblastoma based on bioinformatics (Review).Oncology letters · 2025Review
- Application of EGFR-TKIs in brain tumors, a breakthrough in future?Journal of translational medicine · 2025Review
164 more citing papers are in PubMed but not listed here.
Corrections and comments
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- Commented on byOccupy EGFR.2012
Authors and funding
39 authors at 9 institutions in 1 country.
Funding
Abstract
unlabelledActivation of the epidermal growth factor receptor (EGFR) in glioblastoma (GBM) occurs through mutations or deletions in the extracellular (EC) domain. Unlike lung cancers with EGFR kinase domain (KD) mutations, GBMs respond poorly to the EGFR inhibitor erlotinib. Using RNAi, we show that GBM cells carrying EGFR EC mutations display EGFR addiction. In contrast to KD mutants found in lung cancer, glioma-specific EGFR EC mutants are poorly inhibited by EGFR inhibitors that target the active kinase conformation (e.g., erlotinib). Inhibitors that bind to the inactive EGFR conformation, however, potently inhibit EGFR EC mutants and induce cell death in EGFR-mutant GBM cells. Our results provide first evidence for single kinase addiction in GBM and suggest that the disappointing clinical activity of first-generation EGFR inhibitors in GBM versus lung cancer may be attributed to the different conformational requirements of mutant EGFR in these 2 cancer types. SIGNIFICANCE: Approximately 40% of human glioblastomas harbor oncogenic EGFR alterations, but attempts to therapeutically target EGFR with first-generation EGFR kinase inhibitors have failed. Here, we demonstrate selective sensitivity of glioma-specific EGFR mutants to ATP-site competitive EGFR kinase inhibitors that target the inactive conformation of the catalytic domain.
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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.