Eph receptors as therapeutic targets in glioblastoma

The dismal outlook for patients with the most aggressive and common form of adult brain cancer, glioblastoma (GBM), motivates a search for new therapeutic strategies and targets for this aggressive disease. Here we review the findings to date on the role of Eph family receptor tyrosine kinases and their ephrin ligands in brain cancer. Expression of the Eph family of cell surface proteins is generally downregulated to very low levels in normal adult tissues making them particularly attractive for directed therapeutic targeting. Recent Eph targeting studies in pre-clinical models of GBM have been very encouraging and may provide an avenue to treat these highly refractory aggressive tumours.

• Publication year

  2014

• Venue

  British Journal of Cancer

• Publication date

  2014-08-21

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/bjc.2014.73PMID 25144626PMCID 4183860
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The somatic genomic landscape of glioblastoma.

  2013cited by this paper
• EphA3 maintains tumorigenicity and is a therapeutic target in glioblastoma multiforme.

  2013influential reference
• Loss of miR-204 expression enhances glioma migration and stem cell-like phenotype.

  2013cited by this paper
• Therapeutic targeting of EPH receptors and their ligands

  2013cited by this paper
• EphB4 is overexpressed in gliomas and promotes the growth of glioma cells

  2013cited by this paper
• Identification of cell surface targets through meta-analysis of microarray data.

  2012cited by this paper
• The EphA2 receptor drives self-renewal and tumorigenicity in stem-like tumor-propagating cells from human glioblastomas.

  2012influential reference
• EphB2 receptor controls proliferation/migration dichotomy of glioblastoma by interacting with focal adhesion kinase

  2012cited by this paper
• Expression of EphrinB2 and EphB4 in glioma tissues correlated to the progression of glioma and the prognosis of glioblastoma patients

  2012cited by this paper
• Delta-Like Ligand 4 Correlates with Endothelial Proliferation and Vessel Maturation in Human Malignant Glioma

  2012cited by this paper
• Phase 1, open-label study of MEDI-547 in patients with relapsed or refractory solid tumors

  2012cited by this paper
• Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma.

  2011cited by this paper
• DLL4-Notch signaling mediates tumor resistance to anti-VEGF therapy in vivo.

  2011cited by this paper
• Role of MicroRNA-26b in Glioma Development and Its Mediated Regulation on EphA2

  2011cited by this paper
• Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis

  2010cited by this paper
• Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1.

  2010cited by this paper
• Up-regulation of EphA2 and down-regulation of EphrinA1 are associated with the aggressive phenotype and poor prognosis of malignant glioma

  2010cited by this paper
• Eph receptors and ephrins in cancer: bidirectional signalling and beyond

  2010cited by this paper
• Convection-enhanced delivery for the treatment of brain tumors

  2009cited by this paper
• EphrinA5 acts as a tumor suppressor in glioma by negative regulation of epidermal growth factor receptor

  2009cited by this paper
• EphA2 mediates ligand-dependent inhibition and ligand-independent promotion of cell migration and invasion via a reciprocal regulatory loop with Akt.

  2009cited by this paper
• The phosphorylation of ephrin‐B2 ligand promotes glioma cell migration and invasion

  2009cited by this paper
• Transcriptional switch of dormant tumors to fast-growing angiogenic phenotype.

  2009cited by this paper
• Malignant gliomas in adults.

  2008cited by this paper
• Increased expression of EphA2 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients.

  2008cited by this paper
• Increased expression of EphA7 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients

  2008cited by this paper
• EphA4 promotes cell proliferation and migration through a novel EphA4-FGFR1 signaling pathway in the human glioma U251 cell line

  2008cited by this paper
• Interleukin-13 Receptor α2, EphA2, and Fos-Related Antigen 1 as Molecular Denominators of High-Grade Astrocytomas and Specific Targets for Combinatorial Therapy

  2008cited by this paper
• This work is licensed under the Creative Commons Attribution-Noncommercial-

  2008cited by this paper
• Identification of EphB6 variant-derived epitope peptides recognized by cytotoxic T-lymphocytes from HLA-A24+ malignant glioma patients.

  2008cited by this paper
• EphA 4 promotes cell proliferation and migration through a novel EphA 4-FGFR 1 signaling pathway in the human glioma U 251 cell line

  2008cited by this paper
• Soluble monomeric EphrinA1 is released from tumor cells and is a functional ligand for the EphA2 receptor

  2008cited by this paper
• Dendritic cell-based vaccines suppress metastatic liver tumor via activation of local innate and acquired immunity

  2008cited by this paper
• A novel, potent, and specific ephrinA1-based cytotoxin against EphA2 receptor–expressing tumor cells

  2007cited by this paper
• Quantitative radioimmunoPET imaging of EphA2 in tumor-bearing mice

  2007cited by this paper
• A critical role for the EphA3 receptor tyrosine kinase in heart development.

  2007cited by this paper
• Convection-enhanced delivery for treatment of brain tumors

  2007cited by this paper
• Ephrin-A1 is a negative regulator in glioma through down-regulation of EphA2 and FAK.

  2007influential reference
• Expression of EphA2 in Human Astrocytic Tumors: Correlation with Pathologic Grade, Proliferation and Apoptosis

  2007cited by this paper
• Brain tumour stem cells

  2006cited by this paper
• EphB4 controls blood vascular morphogenesis during postnatal angiogenesis

  2006cited by this paper
• Ephrin-B3 ligand promotes glioma invasion through activation of Rac1.

  2006cited by this paper
• A Genome-Wide Screen Reveals Functional Gene Clusters in the Cancer Genome and Identifies EphA 2 as a Mitogen in Glioblastoma

  2006cited by this paper
• A genome-wide screen reveals functional gene clusters in the cancer genome and identifies EphA2 as a mitogen in glioblastoma.

  2006cited by this paper
• Ephrin-A2 reverse signaling negatively regulates neural progenitor proliferation and neurogenesis.

  2005cited by this paper
• The EphA8 receptor induces sustained MAP kinase activation to promote neurite outgrowth in neuronal cells

  2005cited by this paper
• EphA2 as a Novel Molecular Marker and Target in Glioblastoma Multiforme

  2005cited by this paper
• EphB2/R-Ras signaling regulates glioma cell adhesion, growth, and invasion.

  2005cited by this paper
• Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.

  2005cited by this paper
• EphA2 as a glioma-associated antigen: a novel target for glioma vaccines.

  2005cited by this paper
• Role of Synaptojanin 2 in Glioma Cell Migration and Invasion

  2004cited by this paper
• [Detecting protein expression of EphrinB2 ligand and its receptor EphB4 in astrocytoma using confocal laser scanning microscopy].

  2004cited by this paper
• The phosphorylation of EphB2 receptor regulates migration and invasion of human glioma cells.

  2004cited by this paper
• EphA Receptors Direct the Differentiation of Mammalian Neural Precursor Cells through a Mitogen-activated Protein Kinase-dependent Pathway*

  2004cited by this paper
• Identification of a tumor-specific shared antigen derived from an Eph receptor and presented to CD4 T cells on HLA class II molecules.

  2000cited by this paper
• Functional activation of EphA5 receptor does not promote cell proliferation in the aberrant EphA5 expressing human glioblastoma U-118 MG cell line.

  1999cited by this paper
• Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4.

  1998cited by this paper
• Malignant glioma

  1998influential reference
• Dichotomy of astrocytoma migration and proliferation

  1996cited by this paper
• Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation.

  1995cited by this paper
• Ephrin-A 1 is a negative regulator in glioma through down-reguation of EphA 2 and FAK

  year unknowninfluential reference

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• EphB2 receptor tyrosine kinase-mediated excitatory synaptic functions are negatively modulated by MDGA2.

  2025cites this paper
• Spatial transcriptomics of glioblastoma defines biologically and clinically significant reprogramming patterns across unique spatial microenvironments

  2025cites this paper
• Nanotherapy of Glioblastoma—Where Hope Grows

  2025cites this paper
• The role of lncRNAs in the interplay of signaling pathways and epigenetic mechanisms in glioma.

  2025cites this paper
• Beta-human chorionic gonadotropin, carbohydrate antigen 19-9, cancer antigen 125, and carcinoembryonic antigen as prognostic and predictive biological markers in bladder cancer

  2024cites this paper
• Unveiling the therapeutic promise of EphA2 in glioblastoma: a comprehensive review

  2024cites this paper
• Aptamers: ushering in new hopes in targeted glioblastoma therapy

  2024cites this paper
• The Mechanisms and Overcoming Strategies of the Radioresistance in Head and Neck Cancer

  2023cites this paper
• Classification and function of γδT cells and its research progress in anti-glioblastoma

  2023cites this paper
• Molecular Determinants of EphA2 and EphB2 Antagonism Enable the Design of Ligands with Improved Selectivity

  2023cites this paper
• Development and Validation of a Targeted Treatment for Brain Tumors Using a Multi-Drug Loaded, Relapse-Resistant Polymeric Theranostic.

  2023cites this paper
• Hit discovery of novel 2‐phenyl‐substituted 4‐amino–6,7‐dihydro‐5H‐cyclopenta[d]pyrimidines as potential anti‐glioblastoma therapeutics: Design, synthesis, biological evaluation, and computational screening

  2023cites this paper
• Tumor Microenvironment in Glioma Invasion

  2022cites this paper
• Development of immunotherapy for high-grade gliomas: Overcoming the immunosuppressive tumor microenvironment

  2022cites this paper
• Glioblastoma: Current Status, Emerging Targets, and Recent Advances

  2022cites this paper
• Angioregulatory role of miRNAs and exosomal miRNAs in glioblastoma pathogenesis.

  2022cites this paper
• Immune surveillance in glioblastoma: Role of the NKG2D system and novel cell‐based therapeutic approaches

  2022cites this paper
• Alzheimer’s disease-associated P460L mutation in ephrin receptor type A1 (EphA1) leads to dysregulated Rho-GTPase signaling

  2021cites this paper
• Inhibition of DHFR targets the self-renewing potential of brain tumor initiating cells.

  2021cites this paper
• Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

  2021influential citation
• In-silico predictions of deleterious SNPs in Human ephrin type-A receptor 3 (EPHA3) gene

  2021cites this paper
• The update of chimeric antigen receptor (CAR) -T cells therapy in Glioblastoma.

  2020cites this paper
• Extracellular Vesicles Involvement in the Modulation of the Glioblastoma Environment

  2020cites this paper
• Targeting Ephrin Receptor Tyrosine Kinase A2 with a Selective Aptamer for Glioblastoma Stem Cells

  2020cites this paper
• Optimization of EphA2 antagonists based on a lithocholic acid core led to the identification of UniPR505, a new 3α-carbamoyloxy derivative with antiangiogenetic properties.

  2020cites this paper
• Polycomb-mediated repression of EphrinA5 promotes growth and invasion of glioblastoma

  2020cites this paper
• key effector of the pathway regulating glioblastoma cell proliferation

  2020cites this paper
• The Role of RNA and DNA Aptamers in Glioblastoma Diagnosis and Therapy: A Systematic Review of the Literature

  2020cites this paper
• PDCD10-Deficiency Promotes Malignant Behaviors and Tumor Growth via Triggering EphB4 Kinase Activity in Glioblastoma

  2020cites this paper
• Critical role of EphA3 in cancer and current state of EphA3 drug therapeutics

  2020cites this paper
• The effects of ephrinB2 signaling on proliferation and invasion in glioblastoma multiforme.

  2020cites this paper
• Immunotherapy for gliomas: shedding light on progress in preclinical and clinical development

  2020cites this paper
• Drug Conjugates for Targeting Eph Receptors in Glioblastoma

  2020cites this paper
• Role of Erythropoietin in Cerebral Glioma: An Innovative Target in Neuro-Oncology.

  2019cites this paper
• EphA3 is up-regulated by epidermal growth factor and promotes formation of glioblastoma cell aggregates.

  2019cites this paper
• Ligand-dependent EphB4 activation serves as an anchoring signal in glioma cells.

  2019cites this paper
• RETRACTED: The Small Molecule Ephrin Receptor Inhibitor, GLPG1790, Reduces Renewal Capabilities of Cancer Stem Cells, Showing Anti-Tumour Efficacy on Preclinical Glioblastoma Models

  2019cites this paper
• Porous Silicon Nanoparticles for Applications in Nano-medicine

  2019cites this paper
• The cystine/glutamate antiporter xCT is a key regulator of EphA2 S897 phosphorylation under glucose-limited conditions.

  2019cites this paper
• Tyrosine kinase Eph receptor A6 sensitizes glioma‐initiating cells towards bone morphogenetic protein‐induced apoptosis

  2019cites this paper
• Differential Expression Patterns of Eph Receptors and Ephrin Ligands in Human Cancers

  2018cites this paper
• Roles of Eph/ephrin bidirectional signaling during injury and recovery of the central nervous system

  2018influential citation
• An Experimenter's Guide to Glioblastoma Invasion Pathways.

  2018cites this paper
• Tyrosine kinase activity of EphA2 promotes its S897 phosphorylation and glioblastoma cell proliferation.

  2018cites this paper
• Dying to communicate: apoptotic functions of Eph/Ephrin proteins

  2018cites this paper
• UniPR1331, a small molecule targeting Eph/ephrin interaction, prolongs survival in glioblastoma and potentiates the effect of antiangiogenic therapy in mice

  2018cites this paper
• EphA3 Pay-Loaded Antibody Therapeutics for the Treatment of Glioblastoma

  2018cites this paper
• EphA3 maintains radioresistance in head and neck cancers through epithelial mesenchymal transition.

  2018cites this paper
• EPH Profiling of BTIC Populations in Glioblastoma Multiforme Using CyTOF.

  2018cites this paper
• Chimeric antigen receptor T-cell therapy for glioblastoma.

  2017cites this paper
• Coupling Synthetic Antibodies with Mass Cytometry Allows the Development of a Highly Tailored, Multi- Parametric Single Cell Analysis Strategy

  2017cites this paper
• Prognostic values of EphB 1 / B 2 and p-EphB 1 / B 2 expression in non-small cell lung cancer

  2017cites this paper
• MicroRNA-200c increases radiosensitivity of human cancer cells with activated EGFR-associated signaling

  2017cites this paper
• In silico analyses and global transcriptional profiling reveal novel putative targets for Pea3 transcription factor related to its function in neurons

  2017cites this paper
• Paradoxes of the EphB1 receptor in malignant brain tumors

  2017cites this paper
• Multifunctional nanodiamonds in regenerative medicine: Recent advances and future directions

  2017cites this paper
• Prognostic values of EphB1/B2 and p-EphB1/B2 expression in non-small cell lung cancer.

  2017cites this paper
• Quantitative proteomics reveals fundamental regulatory differences in oncogenic HRAS and IDH 1 driven astrocytoma Running title : Signaling and epigenetics in astrocytoma

  2016cites this paper
• Transcriptional networks controlled by SOX2 in glioblastoma stem cells

  2016cites this paper
• EphA2 is a key effector of the MEK/ERK/RSK pathway regulating glioblastoma cell proliferation.

  2016cites this paper
• EphA8 is a prognostic marker for epithelial ovarian cancer

  2016cites this paper
• Identification of an Interfering Ligand Aptamer for EphB2/3 Receptors

  2016cites this paper
• EphrinB 2 drives perivascular invasion and proliferation of glioblastoma stem-like cells

  2016cites this paper
• Quantitative Proteomics Reveals Fundamental Regulatory Differences in Oncogenic HRAS and Isocitrate Dehydrogenase (IDH1) Driven Astrocytoma*

  2016cites this paper
• Targeting Receptor Tyrosine Kinases Using Monoclonal Antibodies: The Most Specific Tools for Targeted-Based Cancer Therapy.

  2016cites this paper
• EphB4/ephrinB2 Contributes to Imatinib Resistance in Chronic Myeloid Leukemia Involved in Cytoskeletal Proteins

  2016cites this paper
• Silencing of CtBP1 suppresses the migration in human glioma cells

  2016cites this paper
• EphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cells

  2016cites this paper
• Receptor tyrosine kinase expression of circulating tumor cells in small cell lung cancer

  2015cites this paper
• Ephs and Ephrins in malignant gliomas

  2014cites this paper
• Homotypic receptor-receptor interactions regulating Eph signaling

  2014cites this paper
• EphA3 biology and cancer

  2014cites this paper
• Surgery of brain tumors in the older persons

  2014cites this paper
• Eph family co-expression patterns define unique clusters predictive of cancer phenotype

  2014cites this paper
• RETRACTED: The Small Molecule Ephrin Receptor Inhibitor, GLPG1790, Reduces Renewal Capabilities of Cancer Stem Cells, Showing Anti-Tumour Efficacy on Preclinical Glioblastoma Models

  year unknowncites this paper