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    GENE:

    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)

    i
    Other names: NTRK2, TRKB, Neurotrophic tyrosine kinase, receptor, type 2
    5d
    Re-verification and Report Ruling Revision of NTRK Fusion Results of Idylla GeneFusion Assay after Manufacturer Algorithm Update (AMP 2024)
    Our standard operating procedure (SOP) was updated to perform orthogonal confirmation testing for stand-alone equivocal NTRK1/2 and equivocal NTRK3 (5' failure), but to ignore equivocal NTRK3 (5' intact) and report as NTRK2/3 indeterminate. Re-verification showed no change to ALK, ROS1, RET, MET ex14, and NTRK1 results. Sensitivity of NTRK2 detection was significantly increased (80% after orthogonal testing).
    ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • MET exon 14 mutation • ALK fusion • ROS1 fusion • NTRK fusion
    |
    Idylla™ GeneFusion Assay
    5d
    Comparative Analysis of Variant Reporting and HRD Performance: Evaluating AVENIO Tumor Tissue CGP Automated Assay Against F1CDx Assay and PGDx elio Test (AMP 2024)
    The AVENIO CGP Assay demonstrated high agreement with 2 established CGP tests, F1CDx and PGDx, in variant reporting, and closely aligned with F1CDx in HRDsig analysis across various tissue types. These results highlight the assay's reliability and demonstrate its utility in translational research.
    Tumor mutational burden
    |
    HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • HRD (Homologous Recombination Deficiency)
    |
    HER-2 amplification • HRD • ALK rearrangement • RET rearrangement • HRD signature
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    FoundationOne® CDx • AVENIO Tumor Tissue CGP Kit • PGDx elio™ tissue complete assay
    5d
    Frequency of FDA-Approved Companion Diagnostic Biomarkers in Solid Tumors (AMP 2024)
    Genomic profiling yields clinically actionable information for approved therapies and evidence of resistance, and it may uncover rational therapeutic opportunities regardless of tumor type.
    Tumor mutational burden • Companion diagnostic • BRCA Biomarker • MSi-H Biomarker • BRCA Companion diagnostic • MSi-H Companion diagnostic
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
    |
    BRAF V600E • KRAS mutation • BRCA2 mutation • TMB-H • MSI-H/dMMR • KRAS G12C • HER-2 negative • PIK3CA mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ROS1 fusion • KRAS G12 • KRAS exon 2 mutation • ALK-ROS1 fusion
    |
    OncoExTra™ test
    5d
    Comparison of Clinical Sensitivity for Kinase Fusion Detection in Thyroid Carcinoma by Paired Primer Targeted Methods (AMP 2024)
    AFP, the targeted, breakpoint/fusion partner agnostic panel, outperformed 3 other established panels using real-world, fusion-driven thyroid cancers by an average detection frequency of 39%. Such findings demonstrate the importance in sequencing panel selection for fusion-driven thyroid cancer detection, and the potential downstream consequences for diagnostic utility and therapeutic intervention.
    Clinical
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    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
    |
    NTRK1 fusion • FGFR2 fusion • ALK fusion
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    FusionPlex® Dx • Illumina Focus Panel • Oncomine Focus Assay
    5d
    Rapid On-Site Next-Generation Sequencing (NGS) Testing as an Alternative to Single Gene or Send-Out Molecular Testing in Lung and Colon Cancers (AMP 2024)
    Given the importance of timely, comprehensive molecular test results to inform appropriate treatment decisions in NSCLC and CRC, these results suggest that the rapid in-house GeneXus NGS system can reduce TAT with comparable failure rates and alteration detection rates compared to other testing methods. Further studies evaluating the impact of the rapid OPA compared to other methods on patient care, as well as the economics of different molecular tests, are ongoing.
    Next-generation sequencing
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
    |
    KRAS G12C • KRAS G12
    |
    Oncomine Precision Assay
    5d
    Genomic Landscape of Fusions in Solid Tumors Detected by DNA and RNA Comprehensive Genomic Profiling at a Large Community Health System (AMP 2024)
    The routine use of RNA-based CGP analysis allows for the comprehensive detection of oncogenic fusions in patients with cancer. The diversity of tumor types in which actionable fusions were detected supports the broader utilization of CGP to potentially increase targeted therapy usage and improve outcomes across cancer subtypes.
    Tumor mutational burden
    |
    ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    TMB-H • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • PTEN mutation • ALK fusion
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    TruSight Oncology 500 Assay
    11d
    Fusion transcriptome landscape in Glioblastoma (SNO 2024)
    Comprehensive molecular profiling reveals that approximately 10% of IDH WT GBMs carry oncogenic fusions that may be therapeutic targets. Broad spectrum of observed fusions underscores the need for novel clinical trial designs to allow efficient enrollment for prospective testing of potential targeted agents.
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CDK4 (Cyclin-dependent kinase 4) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • SEC61G (SEC61 Translocon Subunit Gamma) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)
    |
    TP53 mutation • EGFR mutation • NTRK1 fusion • NTRK2 fusion • MET amplification • EGFR amplification • ALK fusion • ROS1 fusion • MET mutation • EGFRvIII mutation • FGFR3 fusion • IDH wild-type • EGFR fusion
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    MI Tumor Seek™
    12d
    The genomic landscape of papillary thyroid carcinoma on next-generation sequencing in patients undergoing total thyroidectomy. (PubMed, World J Surg)
    This Indian study identified novel somatic mutations and fusion genes in PTC, revealing a distinct genomic landscape with implications in precision diagnostics and personalized therapies. NGS with intraoperative live sampling shows promise in prognostication and therapeutic optimization of advanced/metastatic PTC cases.
    Journal • Next-generation sequencing
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    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • PTCH1 (Patched 1) • CDH1 (Cadherin 1)
    |
    BRAF mutation • PIK3CA mutation • ALK mutation • PTCH1 mutation
    14d
    Actionable Structural Variant Detection via RNA-NGS and DNA-NGS in Patients With Advanced Non-Small Cell Lung Cancer. (PubMed, JAMA Netw Open)
    Emerging structural variants (eSVs) were found to have a combined prevalence to be 0.7%, with only 47.5% of eSVs detected by DNA-NGS. In this cohort study, the detection of structural variants via concurrent RNA-NGS and DNA-NGS was higher across multiple NCCN-guideline recommended biomarkers compared with DNA-NGS alone, suggesting that RNA-NGS should be routinely implemented in the care of patients with advanced NSCLC.
    Retrospective data • Journal • Next-generation sequencing • Metastases
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    ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
    |
    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • MET exon 14 mutation • ROS1 fusion
    17d
    Targeted Therapy in Salivary Gland Cancer: Prevalence of a Selected Panel of Actionable Molecular Alterations in a German Tertiary Referral Center Patient Cohort. (PubMed, Mol Diagn Ther)
    Our data indicate that targeted therapy using e.g., trastuzumab deruxtecan, bicalutamide, pembrolizumab, cetuximab, entrectinib or sacituzumab govitecan might be a promising option especially for a relevant subset of patients with RM-SGC not suitable for salvage surgery. However, evidence from clinical studies regarding response rates to these therapies remains sparse, which underlines the need of multicenter clinical trials.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • AR (Androgen receptor) • NTRK (Neurotrophic receptor tyrosine kinase) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)
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    HER-2 overexpression • HER-2 amplification • HER-2 expression • EGFR overexpression • TROP2 overexpression • HER-2 elevation • NTRK1 translocation
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    Keytruda (pembrolizumab) • Erbitux (cetuximab) • Rozlytrek (entrectinib) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Trodelvy (sacituzumab govitecan-hziy) • bicalutamide
    19d
    Structural basis for the transmembrane signaling and antidepressant-induced activation of the receptor tyrosine kinase TrkB. (PubMed, Nat Commun)
    We verify the structure using mutagenesis and confirm that the conformation corresponds to the active state of the receptor. Subsequent study of TrkB interaction with the antidepressant drug fluoxetine, and the antipsychotic drug chlorpromazine, provides a clear self-consistent model, describing the mechanism by which fluoxetine activates the receptor by binding to its transmembrane domain.
    Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
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    chlorpromazine • fluoxetine
    20d
    ADVL1823: Larotrectinib in Treating Patients With Previously Untreated TRK Fusion Solid Tumors and TRK Fusion Relapsed Acute Leukemia (clinicaltrials.gov)
    P2, N=70, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2024 --> Sep 2025
    Trial completion date
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    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6)
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    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion
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    Vitrakvi (larotrectinib)
    20d
    ON-TRK: Study to Learn More About the Safety and Effectiveness of the Drug VITRAKVI During Routine Use in Patients With TRK Fusion Cancer Which is Locally Advanced or Spread From the Place Where it Started to Other Places in the Body (clinicaltrials.gov)
    P=N/A, N=150, Recruiting, Bayer | N=300 --> 150
    Enrollment change • Metastases
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    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • NTRK fusion
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    Vitrakvi (larotrectinib)
    21d
    Larotrectinib to Enhance RAI Avidity in Differentiated Thyroid Cancer (clinicaltrials.gov)
    P2, N=13, Recruiting, Children's Hospital of Philadelphia | Trial primary completion date: Oct 2024 --> Oct 2026
    Trial primary completion date
    |
    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion
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    Vitrakvi (larotrectinib)
    24d
    NTRK Gene Expression Analysis in Oral Squamous Cell Carcinoma Mexican Population. (PubMed, Dent J (Basel))
    Our results suggest that NTRK family expression is present in OSCC, with differential expression related to differentiation degree. Additional information about their activation or mutational status could reinforce their potential as a possible primary or adjuvant treatment target.
    Journal
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    NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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    NTRK expression
    28d
    Small Molecule Compound DHPA Screened by Computer-Aided Drug Design and Molecular Dynamics Simulation Inhibits Neuroblastoma Cell Proliferation by Targeting TrkB. (PubMed, ACS Omega)
    Additionally, DHPA can inhibit the expression of TrkB, the activation of TrkB's downstream signaling pathways, and affect the thermal stability of TrkB protein and its response to streptase protease degradation. DHPA may be a potential TrkB inhibitor.
    Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
    1m
    Evaluation of VEGF, BDNF, TRKB expression in oral epithelial dysplasia, oral verrucous carcinoma and oral squamous cell carcinoma and their role as prognostic indicator. (PubMed, J Cancer Res Ther)
    Based on our findings, angiogenesis plays a significant role in tumor growth and metastasis. A substantial relationship was discovered between VEGF, BDNF, TrkB expression, and increases in vascularity throughout the transition from OEDs to VCs and OSCCs.
    Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • VEGFA (Vascular endothelial growth factor A) • BDNF (Brain Derived Neurotrophic Factor)
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    VEGFA expression
    1m
    LMNA::NTRK1 and PRDX1::NTRK1 Atypical Spitz Tumor: A Report of Two Additional Cases With Histological, Immunohistochemical, and Molecular Insights. (PubMed, Am J Dermatopathol)
    Clinical, histopathological, immunohistochemical, and molecular analyses were performed to diagnose these patients. This report adds to the growing body of knowledge on NTRK-rearranged Spitz lesions and underscores the importance of integrating molecular findings with morphological and immunohistochemical data for the accurate classification and understanding of these neoplasms.
    Journal
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    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • PRDX1 (Peroxiredoxin 1) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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    NTRK1 fusion • NTRK2 fusion • LMNA-NTRK1 fusion
    1m
    Analysis of actionable gene fusions in a large cohort of Chinese patients with colorectal cancer. (PubMed, Gastroenterol Rep (Oxf))
    Actionable gene fusions are more prevalent in MSI-H, RAS/BRAF wildtype, or RNF43-mutated CRC, as well as in colon cancer. Mapping of these molecular markers can markedly increase the fusion detection rate, which can help clinicians select candidates for fusion testing and targeted therapy.
    Journal • MSi-H Biomarker
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    BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • RNF43 (Ring Finger Protein 43) • NTRK (Neurotrophic receptor tyrosine kinase)
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    MSI-H/dMMR • BRAF mutation • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • BRAF wild-type • RAS mutation • RNF43 mutation • NTRK fusion
    1m
    S100 and CD34 positive spindle cell tumors of the uterine cervix with EGFR mutation: a hitherto unrecognized neoplasm phenotypically and epigenetically overlapping with "NTRK-rearranged spindle cell neoplasms" of the uterus. (PubMed, Virchows Arch)
    The patient in case 2 had no other known tumors at the time of diagnosis, but no follow-up is available. We believe the reported cases represent a hitherto unrecognized variant of "NTRK-rearranged spindle cell neoplasms" of the uterine cervix with novel EGFR mutations.
    Journal
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    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • TNFRSF8 (TNF Receptor Superfamily Member 8) • CD34 (CD34 molecule) • SOX10 (SRY-Box 10) • NTRK (Neurotrophic receptor tyrosine kinase)
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    EGFR mutation • BRAF mutation • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • TNFRSF8 expression • EGFR exon 20 mutation • CD34 positive
    1m
    A temporal (phospho-)proteomic dataset of neurotrophic receptor tyrosine kinase signalling in neuroblastoma. (PubMed, Sci Data)
    Here, we present a comprehensive label-free mass spectrometry-based total proteomics and phosphoproteomics dataset (432 raw files with FragPipe search outputs; available on PRIDE with accession number PXD054441) where we identified and quantified 4,907 proteins, 16,744 phosphosites and 5,084 phosphoproteins, derived from NGF/BDNF/NT-3 treated TrkA/B/C-overexpressing neuroblastoma cells with differential MYCN status. Analysing our dataset offers valuable insights into TrkA/B/C receptor signalling in neuroblastoma and its modulation by MYCN status; and holds potential for advancing therapeutic strategies in this challenging childhood cancer.
    Journal
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    NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • NTRK (Neurotrophic receptor tyrosine kinase)
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    MYCN amplification • NTRK expression
    1m
    ASPYRE-Lung: validation of a simple, fast, robust and novel method for multi-variant genomic analysis of actionable NSCLC variants in FFPE tissue. (PubMed, Front Oncol)
    The technology is simple and fast, requiring only four reagent transfer steps using standard laboratory equipment (PCR and qPCR instruments) with analysis via a cloud-based algorithm. The ASPYRE-Lung assay has the potential to be transformative in facilitating access to rapid, actionable molecular profiling of tissue for patients with non-small cell carcinoma.
    Journal
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
    |
    MET exon 14 mutation
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    ASPYRE-Lung
    1m
    Clinical Behavior and Molecular Insights of Secretory Carcinoma of Salivary Glands, a Single Center Experience. (PubMed, Indian J Otolaryngol Head Neck Surg)
    in summary, our case series suggests that secretory carcinomas exhibit a favorable clinical course and underscores the pivotal importance of distinguishing secretory carcinomas from other histological subtypes.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
    1m
    ERK signaling promotes resistance to TRK kinase inhibition in NTRK fusion-driven glioma mouse models. (PubMed, Cell Rep)
    Finally, we show that ERK activation promotes resistance to TRK kinase inhibition and identify MEK inhibition as a potential combination therapy. These models will be invaluable tools to study therapy resistance of NTRK fusion tumors.
    Preclinical • Journal
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    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • NTRK fusion
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    Mekinist (trametinib) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
    2ms
    All-in-one bimodal DNA and RNA next-generation sequencing panel for integrative diagnosis of glioma. (PubMed, Pathol Res Pract)
    Overall, our results suggest that the all-in-one bimodal DNA/RNA panel is reliable for detecting diagnostic gene alterations in accordance with the latest WHO classification. The integrative pathological and molecular strategy could be valuable in confirmation of diagnosis and selection of treatment options for brain tumors.
    Journal • Next-generation sequencing
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    EGFR (Epidermal growth factor receptor) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • TERT (Telomerase Reverse Transcriptase)
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    EGFR mutation • NTRK2 fusion • FGFR3 fusion • TERT mutation • IDH mutation + NTRK fusion
    2ms
    A peptide encoded by upstream open reading frame of MYC binds to tropomyosin receptor kinase B and promotes glioblastoma growth in mice. (PubMed, Sci Transl Med)
    The overexpression of MPEP in surgical glioblastoma specimens predicted a poor prognosis, supporting its clinical relevance. In summary, our results demonstrate that tumor-specific translation of a MYC-associated uORF promotes glioblastoma growth, suggesting a new therapeutic strategy for glioblastoma.
    Preclinical • Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
    2ms
    The synergistic effects of anoikis-related genes and EMT-related genes in the prognostic prediction of Wilms tumor. (PubMed, Front Mol Biosci)
    Paclitaxel and mesna were selected as potential chemotherapeutic drugs and adjuvant chemotherapeutic drugs for the WT high-risk group by using the Genomics of Drug Sensitivity in Cancer (GDSC) and cMAP compound libraries, respectively. Next, we selected NTRK2 as the hub gene, and in vitro experiments confirmed that its inhibition can significantly inhibit the proliferation and migration of tumor cells and promote late apoptosis. In summary, we screened out the potential biomarkers and chemotherapeutic drugs that can improve the prognosis of patients with WT.
    Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
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    paclitaxel • mesna
    2ms
    High NTRK2 protein expression levels may be associated with poorer prognosis of breast cancer patients. (PubMed, J Int Med Res)
    Our study demonstrated that higher NTRK2 protein expression is related to a less favorable prognosis in BRCA patients, as well as to enhanced sensitivity to specific chemotherapy and immunotherapy drugs.
    Retrospective data • Journal • BRCA Biomarker • IO biomarker
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • BRCA (Breast cancer early onset) • TYK2 (Tyrosine Kinase 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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    NTRK expression
    2ms
    A pilocytic astrocytoma with novel ATG16L1::NTRK2 fusion responsive to larotrectinib: a case report with genomic and functional analysis. (PubMed, Oncologist)
    Presently, after 22 months of treatment, the patient's complete remission is sustained. Our findings highlight the importance of screening for other oncogenic drivers in BRAF-negative LGGs since rare fusion genes may serve as targets for precision oncology therapy.
    Journal
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    BRAF (B-raf proto-oncogene) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • TYK2 (Tyrosine Kinase 2) • NTRK (Neurotrophic receptor tyrosine kinase) • ATG16L1 (Autophagy Related 16 Like 1)
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    NTRK2 fusion • NTRK fusion
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    Vitrakvi (larotrectinib)
    2ms
    Identification of miR-20a as a Diagnostic and Prognostic Biomarker in Colorectal Cancer: MicroRNA Sequencing and Machine Learning Analysis. (PubMed, Microrna)
    To better define the role of these miRNAs, the ceRNA network, including lncRNAs, was also prepared. In conclusion, the combination of R data analysis and machine learning provides a robust approach to resolving complicated interactions between miRNAs and their targets.
    Journal • Machine learning
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    EGFR (Epidermal growth factor receptor) • ER (Estrogen receptor) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • SMAD4 (SMAD family member 4) • IGF1 (Insulin-like growth factor 1) • MIR21 (MicroRNA 21) • TLR4 (Toll Like Receptor 4) • CDC42 (Cell Division Cycle 42) • MIR19B1 (MicroRNA 19b-1) • PRKCA (Protein Kinase C Alpha) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1) • MIR20A (MicroRNA 20a) • SMAD2 (SMAD Family Member 2) • MIR542 (MicroRNA 542)
    2ms
    Stimulating myelin restoration with BDNF: a promising therapeutic approach for Alzheimer's disease. (PubMed, Front Cell Neurosci)
    BDNF binds with high-affinity on the TrkB neurotrophin receptor and enhances myelination by increasing the density of oligodendrocyte progenitor cells (OPCs) and playing an important role in CNS myelination. Conclusively, in the present review, we discuss the myelin pathophysiology in Alzheimer's Diseases, as well as the role of neurotrophins, and specifically BDNF, in myelin maintenance and restoration, revealing its valuable therapeutic potential against AD.
    Review • Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • BDNF (Brain Derived Neurotrophic Factor)
    2ms
    IDH 2 - a new gene for personalized therapy in pulmonary adenocarcinomas – reports of two cases (ECP 2024)
    Known under low incidence – mutations require research for 0.4% to 1.1 in pulmonary adenocarcinomas, IDH1/2 inhibitors prescription due to high prevalence of lung carcinoma worldwide. Mutations in IDH1/2 gene may be branching drivers leading to lower subclonality evolution with predictable benefit of IDH1/2 inhibitors.The accumulation of more known cases with IDH1/2 mutations is necessary to elucidate clinicopathological characteristics/clinical evolution after target therapy, in order to reforce the new interpretation of malignant tumours postponed survival through conversion of cell cycle.
    Clinical
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ARG1 (Arginase 1)
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    TP53 mutation • KRAS G12C • HER-2 mutation • IDH1 mutation • IDH2 mutation • MET exon 14 mutation • KIT mutation • RET mutation • MET mutation • KRAS G12 • NTRK1 mutation • NTRK1 translocation
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    Oncomine Precision Assay
    2ms
    BPI-28592 as a novel second generation inhibitor for NTRK fusion tumors. (PubMed, NPJ Precis Oncol)
    Clinically, BPI-28592 achieved a complete response in a patient with malignant melanoma carrying an AP3S2-NTRK3 fusion (Clinicaltrials. gov identifier: NCT05302843).
    Journal
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    NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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    NTRK3 fusion • NTRK fusion
    2ms
    Clinical relevance and druggability of sole reciprocal kinase fusions: A large-scale study. (PubMed, Cancer Med)
    This inaugural multicenter study introduces a novel algorithm for detecting and treating sole reciprocal fusions in advanced cancers, expanding the patient population potentially amenable to KIs.
    Clinical • Journal
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    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
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    NTRK1 fusion • NTRK2 fusion • ALK fusion • ROS1 positive • NRG1 fusion
    2ms
    Developing a novel neutralizing monoclonal antibody against TrkB. (PubMed, 3 Biotech)
    Additionally, it is considered a promising candidate for humanization, which would facilitate its application in cancer treatment. The online version contains supplementary material available at 10.1007/s13205-024-04063-x.
    Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CASP3 (Caspase 3) • CASP9 (Caspase 9)
    2ms
    Long-Term Tumor Stability After First-Line Treatment With Larotrectinib in an Infant With NTRK2 Fusion-Positive High-Grade Glioma. (PubMed, J Natl Compr Canc Netw)
    Both larotrectinib and entrectinib are tropomyosin receptor kinase inhibitors with tissue-agnostic approvals for the treatment of patients with solid tumors harboring an NTRK fusion. To our knowledge, this is the first report of a patient with an infantile HGG receiving targeted therapy as first-line treatment with prolonged stable disease. A prospective study of larotrectinib in patients with newly diagnosed infant HGG is ongoing, and will hopefully help answer questions about durability of response, the need for additional therapies, and long-term toxicities seen with TRK inhibitors.
    Journal
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    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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    NTRK2 fusion • ALK fusion • ROS1 fusion • MET fusion • NTRK positive • NTRK fusion
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    Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
    2ms
    The study on circRNA profiling uncovers the regulatory function of the hsa_circ_0059665/miR-602 pathway in breast cancer. (PubMed, Sci Rep)
    Further molecular mechanism studies showed that hsa_circ_0059665 exerts its anticancer gene role by acting as a molecular sponge for miR-602. In our study, we constructed and analyzed a circRNA-related ceRNA regulatory network and found that hsa_circ_0059665 can act as a sponge for miR-602 and inhibit the proliferation, invasion and migration of breast cancer cells.
    Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CAV1 (Caveolin 1) • FGF2 (Fibroblast Growth Factor 2)
    2ms
    Effects of Intermittent Hypoxia in Upper and Lower Limb Functions in Persons With Incomplete Spinal Cord Injury (clinicaltrials.gov)
    P=N/A, N=68, Recruiting, Riphah International University | Not yet recruiting --> Recruiting | Trial completion date: Sep 2023 --> Nov 2024 | Trial primary completion date: Aug 2023 --> Oct 2024
    Enrollment open • Trial completion date • Trial primary completion date
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • BDNF (Brain Derived Neurotrophic Factor)
    3ms
    The Bioactive Gamma-Oryzanol from Oryza sativa L. Promotes Neuronal Differentiation in Different In Vitro and In Vivo Models. (PubMed, Antioxidants (Basel))
    Furthermore, computational analysis suggested ORY's single components have different affinities for the Keap1-Kelch domain. In conclusion, although more in-depth studies are needed, our findings position ORY as a potential source of bioactive molecules with neuro-differentiating potential involving the Nrf2 pathway.
    Preclinical • Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • KEAP1 (Kelch Like ECH Associated Protein 1) • NEUROG1 (Neurogenin 1)
    3ms
    RNASARC - Molecular Screening Program of Soft Tissue Sarcomas With Complex Genomic Profile to Detect NTRK1/2/3, ROS1 or ALK Gene Fusions. (clinicaltrials.gov)
    P=N/A, N=376, Active, not recruiting, Centre Leon Berard | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Feb 2024 --> Dec 2024
    Trial completion date • Trial primary completion date
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    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
    3ms
    Unveiling the protective potential of mirabegron against thioacetamide-induced hepatic encephalopathy in rats: Insights into cAMP/PPAR-γ/p-ERK1/2/p S536 NF-κB p 65 and p-CREB/BDNF/TrkB in parallel with oxidative and apoptotic trajectories. (PubMed, Biochem Pharmacol)
    Mira showed anti-apoptotic activity through inhibition of Bax immunoreactivity and elevation of Bcl2. To summarize, Mira exhibited a hepato-and neuroprotective effect against TAA-induced HE in rats via shielding antioxidant defense and mitigation of the pathological inflammatory and apoptotic axis besides upregulation of neuroprotective signaling pathways.
    Preclinical • Journal
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    BCL2 (B-cell CLL/lymphoma 2) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • TNFA (Tumor Necrosis Factor-Alpha) • PPARG (Peroxisome Proliferator Activated Receptor Gamma) • BDNF (Brain Derived Neurotrophic Factor) • GFAP (Glial Fibrillary Acidic Protein)
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    mirabegron
    3ms
    A behind-the-scenes role of BDNF in the survival and differentiation of spermatogonia. (PubMed, Asian J Androl)
    Inhibition of phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK), and Src pathways all interfere with the growth of BDNF-deficient GSCs. Thus, our findings suggest a role for BDNF in maintaining the undifferentiated state of spermatogonia, particularly in situations where there is a shortage of growth factors.
    Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • PML (Promyelocytic Leukemia) • EGF (Epidermal growth factor) • BDNF (Brain Derived Neurotrophic Factor)