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    GENE:

    EPHA3 (EPH receptor A3)

    i
    Other names: EPHA3, ETK, ETK1, HEK, HEK4, TYRO4, EPH receptor A3
    1m
    A novel oncogenic nonsense mutation of SMARCA4 and genetic characteristic analysis of SMARCA4 (BRG1)-deficient undifferentiated tumor of the bladder. (PubMed, Virchows Arch)
    This suggests that besides SMARCA4 deficiency, alterations in other genes may cooperatively contribute to the tumorigenesis of bladder undifferentiated tumors. These findings provide a reference for subsequent exploration of precise diagnostic and prognostic assessment and treatment strategies for this disease.
    Journal • IO biomarker
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    TP53 (Tumor protein P53) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • KMT2D (Lysine Methyltransferase 2D) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • KMT2C (Lysine Methyltransferase 2C) • FGF3 (Fibroblast growth factor 3) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • FGF4 (Fibroblast growth factor 4) • GLI1 (GLI Family Zinc Finger 1) • STAG2 (Stromal Antigen 2) • FLT4 (Fms-related tyrosine kinase 4) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • EPHA3 (EPH receptor A3)
    1m
    Cooperative interaction between YAP1 and EphA3 receptor tyrosine kinase regulates cellular plasticity and treatment response in prostate cancer. (PubMed, Cell Signal)
    EPHA3 knockout reduces cell proliferation and increases sensitivity to the androgen receptor inhibitor enzalutamide and the YAP1-TEAD inhibitor CA3 in vitro...Bioinformatics analysis further indicates that high YAP1 and EPHA3 correlate with developmental and EMT-related gene signatures. These results demonstrate that the YAP1-EPHA3 axis is a key mediator of cell survival, plasticity, and tumor progression, and may serve as a promising cancer drug target.
    Journal
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    YAP1 (Yes associated protein 1) • RHOA (Ras homolog family member A) • EPHA3 (EPH receptor A3)
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    Xtandi (enzalutamide)
    1m
    The Olive Phenolic S-(-)-Hydroxyoleocanthal Attenuates Neuroendocrine Prostate Cancer via Modulation of EPHA3-Centered Oncogenic Network. (PubMed, Cancers (Basel))
    Treatment with second-generation androgen receptor (AR) inhibitors, such as enzalutamide, can trigger lineage plasticity, promoting the transdifferentiation of PCa cells into an AR-independent, poorly differentiated neuroendocrine phenotype (NEPC)...Conclusions. These findings establish HOC as a multifaceted therapeutic entity capable of disrupting key NEPC oncogenic networks, highlighting its potential as a novel lead intervention for aggressive NEPC.
    Journal
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    EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • DLL3 (Delta Like Canonical Notch Ligand 3) • EPHA3 (EPH receptor A3) • SYP (Synaptophysin) • ASCL1 (Achaete-Scute Family BHLH Transcription Factor 1) • CHGA (Chromogranin A)
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    Xtandi (enzalutamide)
    2ms
    Comparison of the differentially enriched mutations/pathways between stage II and stage IV dMMR/MSI-H colorectal cancer. (PubMed, Sci Prog)
    Sixty-three mutated genes were unique to stage II tumors, while 36 mutated genes were exclusively present in stage IV tumors. Pathway analyses demonstrated the PI3K-AKT pathway was shared by both stage II and stage IV tumors, whereas multiple other signaling pathways showed disease stage-specific enrichment.ConclusionThere were profound differences in mutational profile and molecular mechanisms between stage II and stage IV dMMR/MSI-H CRC.
    Clinical • Retrospective data • Journal • MSi-H Biomarker • MSI-H • dMMR
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    MSI (Microsatellite instability) • FGFR1 (Fibroblast growth factor receptor 1) • STK11 (Serine/threonine kinase 11) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • TSC2 (TSC complex subunit 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • MTHFR (Methylenetetrahydrofolate Reductase) • EPHA3 (EPH receptor A3) • SMAD3 (SMAD Family Member 3)
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    MSI-H/dMMR • STK11 mutation
    4ms
    Beyond cell-cell contact: therapeutic potential of Eph signaling in central nervous system tumors. (PubMed, Front Mol Neurosci)
    The dualistic nature of Eph/ephrin signaling underscores its translational promise as both a biomarker framework and a precision-guided therapeutic target. Combinatorial receptor-ligand modulation strategies may advance the treatment of central nervous system malignancies by exploiting the context-dependent roles of Eph/ephrin interactions.
    Review • Journal
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    ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • EPHA2 (EPH receptor A2) • EPHA3 (EPH receptor A3) • EPHB1 (EPH Receptor B1) • EFNA1 (Ephrin A1) • EFNA5 (Ephrin A5) • EPHA4 (EPH Receptor A4)
    4ms
    Multi-receptor targeted therapy of breast cancer and brain metastases with a novel QUAD-drug conjugate. (PubMed, Breast Cancer Res)
    QUAD-DM1 is a novel multivalent drug conjugate that appears to be highly suitable for the treatment of breast cancer and related brain metastases. The drug candidate can be administered systemically, due to its favorable toxicity profile, or loco-regionally.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • EPHA3 (EPH receptor A3) • EPHB2 (EPH Receptor B2) • IL13 (Interleukin 13)
    6ms
    Molecular analysis of lung adenocarcinomas from the SAFIR02-Lung cohort reveals new metastasis-associated copy-number alterations including frequent mutant-specific KRAS-allelic imbalance and identifies CDKN2A homozygous deletions as an independent biomarker of poor prognosis. (PubMed, Br J Cancer)
    Advanced LUAD tumours exhibit higher copy-number alteration burden, with distinct alterations associated with tumour progression and metastasis. CDKN2A homozygous deletions predict poor prognosis in early disease, while KRAS mutant allele-specific imbalance is enriched in advanced tumours.
    Journal
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • EPHA3 (EPH receptor A3) • PAX8 (Paired box 8) • TNN (Tenascin N)
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    KRAS mutation • CDKN2A deletion
    6ms
    EphA3/EFNA3 Reverse Signalling Promotes Epithelial-to-Mesenchymal Transition via ERK Pathway to Facilitate Colorectal Cancer Metastasis. (PubMed, Dig Dis Sci)
    Our findings suggest that EFNA3 promotes CRC metastasis, and that EphA3/EFNA3 signalling may promote EMT by activating the ERK signalling. These results indicate that the EphA3/EFNA3 axis could be a potential target for metastatic CRC.
    Journal
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    EPHA3 (EPH receptor A3) • EFNA3 (Ephrin A3)
    7ms
    EphA2 and Ephrin-A1 Utilize the Same Interface for Both in cis and in trans Interactions That Differentially Regulate Cell Signaling and Function. (PubMed, bioRxiv)
    Moreover, the cis interaction interferes with ligand binding in trans , attenuates EphA2 canonical signaling. Our results uncover a new mechanism of EphA2 regulation by its co-expressed ligand ephrin-A1 with important implications in its known roles in oncogenesis as well as other disease processes including development of cataract.
    Journal
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    EPHA3 (EPH receptor A3) • EFNA1 (Ephrin A1) • EFNA3 (Ephrin A3) • EFNA5 (Ephrin A5) • EPHA4 (EPH Receptor A4)
    7ms
    Development of a specific anti-human EphA3 monoclonal antibody, Ea3Mab-20, for flow cytometry. (PubMed, Biochem Biophys Rep)
    Furthermore, Ea3Mab-20 demonstrated the suitability for detecting formalin-fixed paraffin-embedded cell samples in immunohistochemistry. Therefore, Ea3Mab-20 is valuable mAb for basic research and is expected to contribute to the clinical application of mAb for cancer therapy and diagnosis.
    Journal
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    EPHA3 (EPH receptor A3)
    8ms
    Feasibility of long-read sequencing to identify molecular alterations in an Indonesian cohort of locally advanced to advanced nasopharyngeal cancer. (PubMed, Sci Rep)
    Extensive DNA repair gene defects, primarily complex SVs detectable by long reads, were observed and highly possibly associated with poor survival. These findings underscore the potential of long-read sequencing for uncovering clinically relevant mutations in NPC.
    Journal
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    FADD (Fas associated via death domain) • ZFHX3 (Zinc Finger Homeobox 3) • CASP8 (Caspase 8) • EPHA3 (EPH receptor A3) • CDKN1C (Cyclin Dependent Kinase Inhibitor 1C) • IRF5 (Interferon Regulatory Factor 5)
    9ms
    Promoter hypermethylation of SFRP1 is an allele fraction-dependent prognostic biomarker in metastatic pancreatic ductal adenocarcinoma. (PubMed, Front Oncol)
    phSFRP1low had a worse prognosis than umSFRP1 at only 12 months, indicating dynamic changes. This could help personalize the treatment of PDAC.
    Journal
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    EPHA3 (EPH receptor A3) • SFRP1 (Secreted frizzled related protein 1)