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    GENE:

    NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3)

    i
    Other names: NTRK3, TRKC, Neurotrophic tyrosine kinase, receptor, type 3
    2d
    Impact of combined exercise on blood DNA methylation and physical health in older women with obesity. (PubMed, PLoS One)
    Despite these significant molecular changes, there was no observable difference in DNAm age after the intervention. This study highlights how combined exercise can modify DNAm patterns in older women, particularly in lipogenesis-related genes, but suggests that further research is needed to understand the full implications for biological ageing.
    Journal • Epigenetic controller
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    NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • CCL11 (C-C Motif Chemokine Ligand 11)
    2d
    Comprehensive study of gene fusions in sarcomas. (PubMed, Invest New Drugs)
    Genomic profiling of sarcomas offers valuable insights into their molecular drivers and can support personalized therapeutic approaches. Further research is needed to validate these findings and optimize treatment strategies for sarcoma patients.
    Journal
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    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • CDK4 (Cyclin-dependent kinase 4) • EWSR1 (EWS RNA Binding Protein 1) • FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor) • HMGA2 (High mobility group AT-hook 2) • STAT6 (Signal transducer and activator of transcription 6) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex) • NAB2 (NGFI-A Binding Protein 2)
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    ALK fusion
    5d
    Unveiling Diagnostic Clues of NTRK-Rearranged Spindle Cell Neoplasms in Fine-Needle Aspiration Specimens. (PubMed, Cytopathology)
    NTRK-rearranged spindle cell tumours' definitive diagnosis enables targeted therapy. Fine-needle aspiration cytology, being minimally invasive, offers the potential for earlier and more definitive diagnoses, thereby improving patient treatment options.
    Journal
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    NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
    6d
    Transdifferentiation of Secretory Carcinoma to Metaplastic Carcinoma at Metastatic Site. (PubMed, Int J Surg Pathol)
    Herein we describe a patient with secretory carcinoma showing transdifferentiation into metaplastic carcinoma (spindle cell and squamous cell carcinoma) at the metastatic site following treatment. Identification of these morphologic shifts is crucial for accurate classification and identification of potential resistant mechanisms.
    Journal • Metastases
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    NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase)
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    NTRK3 fusion
    7d
    NTRK-rearranged spindle cell tumor with SPECC1L-NTRK3 fusion in the thoracic spine: a case report. (PubMed, J Cancer Res Clin Oncol)
    Following 1 month of entrectinib treatment, the patient experienced considerable tumor shrinkage and symptomatic improvement. For bone-derived NTRK-rearranged spindle cell sarcomas, entrectinib shows promising therapeutic efficacy and should be considered a preferred treatment option.
    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) • SPECC1L (Sperm Antigen With Calponin Homology And Coiled-Coil Domains 1 Like)
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    NTRK3 fusion
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    Rozlytrek (entrectinib)
    12d
    Soft tissue tumor with BRAF and NRAS mutations sharing features with NTRK-rearranged spindle cell neoplasm: A case report expanding the spectrum of spindle cell tumor with kinase gene alterations. (PubMed, Pathol Int)
    Since BRAF activation occurs in BRAF fusion gene tumors and BRAF mutations, they could share a similar mechanism in tumorigenesis. This case suggests the further expansion of kinase-related spindle cell tumors.
    Journal
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    BRAF (B-raf proto-oncogene) • 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) • CD34 (CD34 molecule) • NTRK (Neurotrophic receptor tyrosine kinase)
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    BRAF V600E • BRAF mutation • NRAS mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • NRAS Q61K • NRAS Q61 • BRAF fusion • NRAS mutation + BRAF mutation
    13d
    Clinicopathologic and Molecular Analysis of 15 Pediatric and Young Adult Patients with High-Grade Non-anaplastic Thyroid Carcinoma. (PubMed, Endocr Pathol)
    In this limited case series, two patients were dead at the last follow-up. Whether these findings are consistent within this patient population remains to be addressed as more patient series are published.
    Journal
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    BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • SQSTM1 (Sequestosome 1) • DICER1 (Dicer 1 Ribonuclease III) • NTRK (Neurotrophic receptor tyrosine kinase)
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    BRAF V600E • BRAF V600 • NTRK3 fusion
    16d
    Receptor tyrosine kinase fusion-mediated resistance to EGFR-TKI in EGFR-mutant NSCLC: a multi-center analysis and literature review. (PubMed, J Thorac Oncol)
    Emergence of RTK fusions is one of the mechanisms of bypass resistance of EGFR TKI. Dual inhibition of EGFR-RTK was safe and efficacious in patients with targetable RTK fusion post progression on EGFR TKIs.
    Review • Journal
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    BRAF (B-raf proto-oncogene) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK (Neurotrophic receptor tyrosine kinase)
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    EGFR mutation • RET fusion • ALK fusion • ROS1 fusion
    22d
    DB-1311-O-1001: A Study of DB-1311 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=450, Recruiting, DualityBio Inc. | N=280 --> 450 | Trial completion date: Apr 2025 --> Sep 2026 | Trial primary completion date: Apr 2025 --> Sep 2026
    Enrollment change • Trial completion date • Trial primary completion date • Metastases
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    EGFR (Epidermal growth factor receptor) • 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) • CD276 (CD276 Molecule)
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    BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • ALK rearrangement • MET exon 14 mutation • ROS1 rearrangement • MET mutation • RET rearrangement • KRAS G12 • NTRK1 mutation
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    BNT324
    23d
    Case report: STRN3-NTRK3 fusion in uterine sarcoma with spleen metastasis: a new variant in the spectrum of NTRK-rearranged tumors. (PubMed, Front Med (Lausanne))
    The fusion involved STRN3 (exon-3) and NTRK3 (exon-14) genes and was identified through next-generation sequencing analysis. Recognizing this specific molecular rearrangement is crucial, as it not only enables targeted therapy but also holds diagnostic significance in specific clinical scenarios.
    Journal
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    NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK (Neurotrophic receptor tyrosine kinase)
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    NTRK3 fusion
    29d
    ADVL1823: Larotrectinib in Treating Patients With Previously Untreated TRK Fusion Solid Tumors and TRK Fusion Relapsed Acute Leukemia (clinicaltrials.gov)
    P2, N=31, Active, not recruiting, Children's Oncology Group | N=70 --> 31
    Enrollment change
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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)
    1m
    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
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    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)
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    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
    1m
    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)
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    NTRK1 fusion • FGFR2 fusion • ALK fusion
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    FusionPlex® Dx • Illumina Focus Panel • Oncomine Focus Assay
    1m
    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)
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    KRAS G12C • KRAS G12
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    Oncomine Precision Assay
    1m
    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
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    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)
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    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
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    OncoExTra™ test
    1m
    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
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    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)
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    TMB-H • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • PTEN mutation • ALK fusion
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    TruSight Oncology 500 Assay
    1m
    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)
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    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • MET exon 14 mutation • ALK fusion • ROS1 fusion • NTRK fusion
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    Idylla™ GeneFusion Assay
    1m
    The oncogenic Flip in patients with leptomeningeal metastatic disease (LMD): Longitudinal detection in cerebrospinal fluid tumor cells (CSF-TCs) reveals implications for differential treatment of the LMD tumor (SNO 2024)
    CNSide can be used to detect oncogene amplification on CSF-TCs of patients with LMD, and mutational status of the LMD tumor may differ from the original tumor biopsy. CSF-TC analysis may provide therapeutic insights that vary from the original tumor and could open the door to additional treatment targets for patients struck with LMD.
    Clinical • PD(L)-1 Biomarker • IO biomarker • Tumor cell • Metastases
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • 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) • FGFR1 (Fibroblast growth factor receptor 1)
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    CNSide™ Cerebrospinal Fluid Assay
    1m
    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)
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    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™
    1m
    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)
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    BRAF mutation • PIK3CA mutation • ALK mutation • PTCH1 mutation
    1m
    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)
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    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • MET exon 14 mutation • ROS1 fusion
    2ms
    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
    2ms
    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)
    2ms
    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)
    2ms
    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
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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
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    Vitrakvi (larotrectinib)
    2ms
    Clinicopathologic characterization of secretory carcinoma of salivary gland. (PubMed, World J Surg Oncol)
    SCSG is a rare low-grade malignancy with a good prognosis. Pathological and immunohistochemical characteristics are the key to secretory carcinoma (SC) diagnosis, and surgical excision is the major treatment means for SCSG. Whether to perform simultaneous cervical lymph node dissection and other adjuvant therapies should be determined based on the pathological stage and the presence or absence of high-risk factors.
    Retrospective data • Journal
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    NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6)
    2ms
    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
    2ms
    Comprehensive Genomic Assessment of Advanced-Stage GI Stromal Tumors Using the Japanese National Center for Cancer Genomics and Advanced Therapeutics Database. (PubMed, JCO Precis Oncol)
    This study highlights the genomic landscape of advanced GISTs and the important role of CGP in identifying rational molecular-targeted therapeutic options.
    Retrospective data • Journal • Tumor mutational burden • PD(L)-1 Biomarker • Stroma • Metastases
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    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • STK11 (Serine/threonine kinase 11) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ETV6 (ETS Variant Transcription Factor 6) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • NTRK (Neurotrophic receptor tyrosine kinase) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
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    TMB-H • NTRK3 fusion • HRD • ETV6-NTRK3 fusion • PDGFRA mutation • PDGFR wild-type
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    Keytruda (pembrolizumab)
    2ms
    Do not Judge a book by its Cover: A Secretory Carcinoma Arising from a Salivary Gland Heterotopia in Laterocervical lymph-node. (PubMed, Head Neck Pathol)
    Tumours arising on HSGT, share histological similarities with those affecting orthotopic salivary glands. This unique case expands the understanding of SC occurrences on HSGT.
    Journal
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    NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6)
    |
    NTRK3 fusion • ETV6-NTRK3 fusion
    2ms
    Mammary analogue secretory carcinoma involving submandibular gland: Diagnostic pitfall with review of literature. (PubMed, J Cancer Res Ther)
    Prognosis of MASC is comparable to other low grade salivary gland malignancies; however, aggressive behavior has also been reported in few cases. This case is one of the very few reported cases describing MASC with detailed clinical, cytology, and microscopy findings along with special stains and immunohistochemistry.
    Review • Journal
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    NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6)
    |
    NTRK3 translocation
    2ms
    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)
    |
    NTRK1 fusion • NTRK2 fusion • LMNA-NTRK1 fusion
    2ms
    Descriptive Analysis of Common Fusion Mutations in Papillary Thyroid Carcinoma in Hungary. (PubMed, Int J Mol Sci)
    The frequent occurrence of fusion mutations and their associations with certain clinicopathological metrics highlight the importance of integrating molecular profiling into routine PTC management. Early detection of fusion mutations can inform surgical decisions and therapeutic strategies, potentially improving clinical outcomes.
    Retrospective data • Journal
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    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • CCDC6 (Coiled-Coil Domain Containing 6) • ETV6 (ETS Variant Transcription Factor 6) • NCOA4 (Nuclear Receptor Coactivator 4) • SQSTM1 (Sequestosome 1)
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    BRAF V600E • BRAF V600
    2ms
    Crizotinib (Xalkori) Expanded Access Protocol for the Treatment of Adult or Pediatric Patients (clinicaltrialsregister.eu)
    P4, N=14, Pfizer, Inc
    New P4 trial
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    ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6)
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    NTRK3 fusion • ALK mutation • ETV6-NTRK3 fusion • ALK translocation
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    Xalkori (crizotinib)
    2ms
    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
    2ms
    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
    2ms
    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
    2ms
    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)
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    MET exon 14 mutation
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    ASPYRE-Lung
    2ms
    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)
    3ms
    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)
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    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • NTRK fusion
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    Mekinist (trametinib) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
    3ms
    microRNA profiling augments mutation status in the risk stratification of thyroid nodules with a Suspicious for Malignancy (Bethesda V) cytology diagnosis (ATA 2024)
    miRNA pairwise expression profiling enhances the miRNA algorithmic classifier and mutation status in assessing malignancy risk and allowed for further stratification of both RAS-positive and mutation-negative Bethesda V thyroid nodules.
    Late-breaking abstract • Cytology
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    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3)
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    BRAF V600E • BRAF V600 • ALK fusion • RAS mutation
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    ThyGeNEXT® + ThyraMIR®
    3ms
    DNA and RNA Comprehensive Genomic Profiling are Complementary for Detection of Clinically Relevant Fusions in Papillary Thyroid Carcinoma (ATA 2024)
    As demonstrated in our PTC cohort, DNA CGP and RNA CGP may be complementary for fusion detection in certain tumor types. RNA CGP complements DNA CGP by detecting fusions that cannot be efficiently baited on DNA CGP, while DNA CGP may complement RNA CGP by detecting fusions in poor quality (e.g., old archival) samples when RNA sequencing may not be not technically feasible. Clinically relevant fusions detected in this retrospectively profiled PTC cohort included therapeutically targetable fusion events (e.g., RET, NTRK, ALK) and a PAX8::PPARG fusion, which is suggestive of a follicular variant PTC.
    Clinical • Late-breaking abstract
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    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • CCDC6 (Coiled-Coil Domain Containing 6) • ETV6 (ETS Variant Transcription Factor 6) • TPM3 (Tropomyosin 3) • NTRK (Neurotrophic receptor tyrosine kinase) • PPARG (Peroxisome Proliferator Activated Receptor Gamma) • RBPMS (RNA-binding protein with multiple splicing) • PAX8 (Paired box 8)
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    NTRK3 fusion • RET fusion • ALK fusion
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    FoundationOne® CDx • FoundationOne®RNA
    3ms
    Unmasking the rarity of mammary analogue secretory carcinoma of the minor salivary gland - A case report. (PubMed, Int J Surg Case Rep)
    MASC is an important molecularly defined entity of the salivary gland with low-grade malignant potential. Correct diagnosis is essential for appropriate treatment and will help to provide better information about this potentially low-grade malignant salivary gland neoplasm.
    Journal
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    NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6)
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    ETV6-NTRK3 fusion