ArticleCancer research2015
A urokinase receptor-Bim signaling axis emerges during EGFR inhibitor resistance in mutant EGFR glioblastoma.
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 36 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
36 citing papers in PubMed, 58 citations in OpenAlex.
- Review
- Radiomics-based gradient boosting model on contrast-enhanced MRI for non-invasive prediction of epidermal growth factor receptor expression and therapeutic response to EGFR-targeted antibody-drug conjugates in high-grade glioma organoid models.Journal of translational medicine · 2026Article
- Combination Cancer Therapy and Reference Models for Assessing Drug Synergy in Glioblastoma.Current oncology (Toronto, Ont.) · 2025Review
- Identifying and exploiting combinatorial synthetic lethality by characterizing adaptive kinome rewiring of EGFRvIII-driven glioblastoma.Acta neuropathologica communications · 2025Article
- Review
- FOSL1's Oncogene Roles in Glioma/Glioma Stem Cells and Tumorigenesis: A Comprehensive Review.International journal of molecular sciences · 2024Review
- From signalling pathways to targeted therapies: unravelling glioblastoma's secrets and harnessing two decades of progress.Signal transduction and targeted therapy · 2023Review
- Glioma Stem Cells Are Sensitized to BCL-2 Family Inhibition by Compromising Histone Deacetylases.International journal of molecular sciences · 2023Article
- Urokinase Receptor uPAR Downregulation in Neuroblastoma Leads to Dormancy, Chemoresistance and Metastasis.Cancers · 2022Article
- Modulation of Cellular Function by the Urokinase Receptor Signalling: A Mechanistic View.Frontiers in cell and developmental biology · 2022Review
- Establishment and characterization of an ovarian yolk sac tumor patient-derived xenograft model.Pediatric surgery international · 2021Article
- The Urokinase Receptor: A Multifunctional Receptor in Cancer Cell Biology. Therapeutic Implications.International journal of molecular sciences · 2021Review
- Xenograft models for pediatric cancer therapies.Faculty reviews · 2021Review
- Epidermal growth factor receptor regulates fibrinolytic pathway elements in cervical cancer: functional and prognostic implications.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2021Article
- EGFRvIII uses intrinsic and extrinsic mechanisms to reduce glioma adhesion and increase migration.Journal of cell science · 2020Article
- S6K1 blockade overcomes acquired resistance to EGFR-TKIs in non-small cell lung cancer.Oncogene · 2020Article
- Glioblastoma Cell Resistance to EGFR and MET Inhibition Can Be Overcome via Blockade of FGFR-SPRY2 Bypass Signaling.Cell reports · 2020Article
- Efficacy of EGFR plus TNF inhibition in a preclinical model of temozolomide-resistant glioblastoma.Neuro-oncology · 2019Article
- EGFR/uPAR interaction as druggable target to overcome vemurafenib acquired resistance in melanoma cells.EBioMedicine · 2019Article
- Patient-derived xenograft mouse models: A high fidelity tool for individualized medicine.Oncology letters · 2019Review
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 2 institutions in 2 countries.
Funding
Abstract
EGFR is the most common genetically altered oncogene in glioblastoma (GBM), but small-molecule EGFR tyrosine kinase inhibitors (TKI) have failed to yield durable clinical benefit. Here, we show that in two novel model systems of acquired resistance to EGFR TKIs, elevated expression of urokinase plasminogen activator (uPA) drives signaling through the MAPK pathway, which results in suppression of the proapoptotic BCL2-family member protein BIM (BCL2L11). In patient-derived GBM cells and genetic GBM models, uPA is shown to suppress BIM levels through ERK1/2 phosphorylation, which can be reversed by siRNA-mediated knockdown of uPA. TKI-resistant GBMs are resensitized to EGFR TKIs by pharmacologic inhibition of MEK or a BH3 mimetic drug to replace BIM function. A link between the uPA-uPAR-ERK1/2 pathway and BIM has not been previously demonstrated in GBM, and involvement of this signaling axis in resistance provides rationale for a new strategy to target EGFR TKI-resistant GBM.
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.