ArticleCancer discovery2012
Kinetics of inhibitor cycling underlie therapeutic disparities between EGFR-driven lung and brain cancers.
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 33 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
33 citing papers in PubMed, 54 citations in OpenAlex.
- GRIP-Lung: Generative Model of Response to Drug-Induced Perturbation in Lung Cancer.International journal of molecular sciences · 2026Article
- EGFR, the Lazarus target for precision oncology in glioblastoma.Neuro-oncology · 2022Review
- Anoctamins and Calcium Signalling: An Obstacle to EGFR Targeted Therapy in Glioblastoma?Cancers · 2022Review
- EGFR ligands dictate tumour suppression.Nature cell biology · 2022Article
- GCN2 kinase activation by ATP-competitive kinase inhibitors.Nature chemical biology · 2022Article
- Kinetics of receptor tyrosine kinase activation define ERK signaling dynamics.Science signaling · 2020Article
- Article
- The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Mechanisms of Resistance to EGFR Inhibition Reveal Metabolic Vulnerabilities in Human GBM.Molecular cancer therapeutics · 2019Article
- Epidermal growth factor receptor and EGFRvIII in glioblastoma: signaling pathways and targeted therapies.Oncogene · 2018Review
- Drug-Target Kinetics in Drug Discovery.ACS chemical neuroscience · 2018Article
- A TNF-JNK-Axl-ERK signaling axis mediates primary resistance to EGFR inhibition in glioblastoma.Nature neuroscience · 2017Article
- InsR/IGF1R Pathway Mediates Resistance to EGFR Inhibitors in Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- CNS Anticancer Drug Discovery and Development Conference White Paper.Neuro-oncology · 2015Article
- Ligand-Independent EGFR Signaling.Cancer research · 2015Review
- Development of Resistance to EGFR-Targeted Therapy in Malignant Glioma Can Occur through EGFR-Dependent and -Independent Mechanisms.Cancer research · 2015Article
- A leak pathway for luminal protons in endosomes drives oncogenic signalling in glioblastoma.Nature communications · 2015Article
- Advances and challenges in the molecular biology and treatment of glioblastoma-is there any hope for the future?Annals of translational medicine · 2015Review
- Targeting molecular addictions in cancer.British journal of cancer · 2014Review
- Identifying Determinants of EGFR-Targeted Therapeutic Biochemical Efficacy Using Computational Modeling.CPT: pharmacometrics & systems pharmacology · 2014Article
Corrections and comments
- Commented on byOccupy EGFR.2012
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledAlthough mutational activation of the epidermal growth factor receptor (EGFR) features prominently in glioma and non-small cell lung cancer (NSCLC), inhibitors of EGFR improve survival only in patients with NCSLC. To understand how mutations in EGFR influence response to therapy, we generated glioma cells expressing either glioma- or NSCLC-derived alleles and quantified kinase-site occupancy by clinical inhibitors with the use of a novel affinity probe and kinetic methodology. At equivalent doses, erlotinib achieved lower kinase-site occupancy in glioma-derived EGFRvIII compared with NSCLC-derived EGFR mutants. Kinase-site occupancy correlated directly with cell-cycle arrest. EGFRvIII released erlotinib rapidly compared with wild-type EGFR, whereas NSCLC-derived mutants released erlotinib slowly. SIGNIFICANCE: These data suggest that kinase-site occupancy is a biomarker for efficacy of EGFR inhibitors, that rapid binding and release of erlotinib in glioma-derived EGFRvIII opposes the blockade of downstream signaling, and that slower cycling of erlotinib within the active site of NSCLC-derived mutants underlies their improved clinical response.
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.