ArticleCancer research2015
Development of Resistance to EGFR-Targeted Therapy in Malignant Glioma Can Occur through EGFR-Dependent and -Independent Mechanisms.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- The efficacy of targeted therapy combined with radiotherapy and temozolomide-based chemotherapy in the treatment of glioma: A systemic review and meta-analysis of phase II/III randomized controlled trials.Frontiers in oncology · 2023Pooled it
- Exploring the landscape of targetable alterations in patients with glioblastoma.Nature reviews. Clinical oncology · 2026Review
- Dysregulation of post-translational modifications in glioma: advances in pathological mechanisms and clinical targeting strategies.Journal of translational medicine · 2026Review
- Article
- WAC, a novel GBM tumor suppressor, induces GBM cell apoptosis and promotes autophagy.Medical oncology (Northwood, London, England) · 2021Article
- Article
- Molecular Mechanisms of Treatment Resistance in Glioblastoma.International journal of molecular sciences · 2020Review
- Epitranscriptomics and epiproteomics in cancer drug resistance: therapeutic implications.Signal transduction and targeted therapy · 2020Review
- PiggyBac mutagenesis and exome sequencing identify genetic driver landscapes and potential therapeutic targets of EGFR-mutant gliomas.Genome biology · 2020Article
- The Role of Liquid Biopsies in Detecting Molecular Tumor Biomarkers in Brain Cancer Patients.Cancers · 2020Review
- Mutation and drug-specific intracellular accumulation of EGFR predict clinical responses to tyrosine kinase inhibitors.EBioMedicine · 2020Article
- Novel approaches to combat chemoresistance against glioblastomas.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- Defining EGFR amplification status for clinical trial inclusion.Neuro-oncology · 2019Article
- The efficacy of a coordinated pharmacological blockade in glioblastoma stem cells with nine repurposed drugs using the CUSP9 strategy.Journal of cancer research and clinical oncology · 2019Article
- Article
- Finding the Right Way to Target EGFR in Glioblastomas; Lessons from Lung Adenocarcinomas.Cancers · 2018Article
- FoxM1 drives ADAM17/EGFR activation loop to promote mesenchymal transition in glioblastoma.Cell death & disease · 2018Article
- Preparation and characterization of Fe3O4@Au-C225 composite targeted nanoparticles for MRI of human glioma.PloS one · 2018Article
- The preliminary radiogenomics association between MR perfusion imaging parameters and genomic biomarkers, and their predictive performance of overall survival in patients with glioblastoma.Journal of neuro-oncology · 2017Article
- Glioblastoma targeted therapy: updated approaches from recent biological insights.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Epidermal growth factor receptor (EGFR) is highly amplified, mutated, and overexpressed in human malignant gliomas. Despite its prevalence and growth-promoting functions, therapeutic strategies to inhibit EGFR kinase activity have not been translated into profound beneficial effects in glioma clinical trials. To determine the roles of oncogenic EGFR signaling in gliomagenesis and tumor maintenance, we generated a novel glioma mouse model driven by inducible expression of a mutant EGFR (EGFR*). Using combined genetic and pharmacologic interventions, we revealed that EGFR*-driven gliomas were insensitive to EGFR tyrosine kinase inhibitors, although they could efficiently inhibit EGFR* autophosphorylation in vitro and in vivo. This is in contrast with the genetic suppression of EGFR* induction that led to significant tumor regression and prolonged animal survival. However, despite their initial response to genetic EGFR* extinction, all tumors would relapse and propagate independent of EGFR*. We further showed that EGFR*-independent tumor cells existed prior to treatment and were responsible for relapse following genetic EGFR* suppression. And, the addition of a PI3K/mTOR inhibitor could significantly delay relapse and prolong animal survival. Our findings shed mechanistic insight into EGFR drug resistance in glioma and provide a platform to test therapies targeting aberrant EGFR signaling in this setting.
Indexed as
Identifiers
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.