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    GENE:

    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)

    i
    Other names: NTRK1, MTC, TRK, TRKA, Neurotrophic tyrosine kinase, receptor, type 1
    1d
    Advanced Intrahepatic Cholangiocarcinoma (iCCA): Investigating Co-Molecular Alterations (AIOM 2024)
    The FGFR and IDH-1 pathways are the primary targets for therapy, with FGFR-2 and IDH-1 inhibitors, such as Pemigatinib and Ivosidenib respectively, already available on the market. This prospective study validates the prevalence of mutations documented in the literature and underscores the significance of NGS in presenting supplementary therapeutic avenues. Moreover, we demonstrated the role of other potential targets co-expressed with FGFR2 or IDH1 which could represent a crucial opportunity for novel combinations or sequences therapies.
    BRCA Biomarker • Metastases
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • MTAP (Methylthioadenosine Phosphorylase) • BAP1 (BRCA1 Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NTRK (Neurotrophic receptor tyrosine kinase) • CA 19-9 (Cancer antigen 19-9)
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    TP53 mutation • KRAS mutation • IDH1 mutation • FGFR2 mutation • FGFR2 fusion • CDKN2A mutation • BAP1 mutation • FGFR2 expression • FGFR2b expression
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    FoundationOne® CDx
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    Pemazyre (pemigatinib) • Tibsovo (ivosidenib)
    1d
    Tissue-based Next Generation Sequencing (NGS) for Patients with Advanced Solid Tumors: the experience of Verona University Hospital (AIOM 2024)
    Our study provides an example of implementation of molecular profiling in an academic pre-screening program. Further analysis will investigate treatment matching rates, drug access schemes, and their impact on treatment efficacy and survival.
    Clinical • Next-generation sequencing • BRCA Biomarker • Metastases
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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) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
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    BRAF V600E • KRAS mutation • BRCA2 mutation • BRCA1 mutation • EGFR mutation • KRAS G12C • HER-2 amplification • PIK3CA mutation • BRAF V600 • NTRK1 fusion • PTEN mutation • KIT mutation • FGFR2 mutation • RET mutation • MET mutation • KRAS G12 • ESR1 mutation • NTRK1 mutation • BRAF amplification
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    FoundationOne® CDx • TruSight Oncology 500 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
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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
    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
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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
    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)
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    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)
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    KRAS G12C • KRAS G12
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    Oncomine Precision Assay
    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)
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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
    11d
    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
    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)
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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™
    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)
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    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)
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    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
    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
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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
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    Vitrakvi (larotrectinib)
    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
    Molecular and Clinical Features of Pancreatic Acinar Cell Carcinoma: A Single-Institution Case Series. (PubMed, Cancers (Basel))
    One patient was found to have RET fusion and responded favorably to selpercatinib for over 42 months...One of the additional two cases who underwent BostonGene testing was found to have NTRK1 fusion. RNA and TME analysis by Boston Gene of the two cases reported immune desert features and relatively lower RNA levels of CEACAM5, CD47, CD74, and MMP1 and higher RNA levels of CDH6 compared with PDAC.
    Journal • BRCA Biomarker
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    KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CD74 (CD74 Molecule) • PALB2 (Partner and localizer of BRCA2) • CEACAM5 (CEA Cell Adhesion Molecule 5) • CDH6 (Cadherin 6) • MMP1 (Matrix metallopeptidase 1)
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    BRCA2 mutation • BRCA1 mutation • NTRK1 fusion • RET fusion • ATM mutation • PALB2 mutation • KRAS wild-type
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    Retevmo (selpercatinib)
    1m
    Hepatoid thymic carcinoma in a polycythemia vera patient treated with ropeginterferon Alfa-2b: Clinical, histopathological and molecular correlates. (PubMed, Pathol Res Pract)
    Whole exome sequencing revealed loss of function mutations in TP53, STK11, PBRM1, SMAD3, FN1, NTRK1, and FANCD2, as well as gain of function mutations in MTOR, BCL11A and COL1A1, along with amplification of CCND3 and MDM2. This mutational landscape halfway between thymic carcinoma (TP53, PBRM1) and hepatoid variant carcinoma of other sites (STK11) suggests that, at some point during carcinogenesis, a switch occurred from an epithelial thymic phenotype to a hepatoid-like one.
    Journal
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    TP53 (Tumor protein P53) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • STK11 (Serine/threonine kinase 11) • mTOR (Mechanistic target of rapamycin kinase) • MDM2 (E3 ubiquitin protein ligase) • PBRM1 (Polybromo 1) • CCND3 (Cyclin D3) • COL1A1 (Collagen Type I Alpha 1 Chain) • FANCD2 (FA Complementation Group D2) • BCL11A (BAF Chromatin Remodeling Complex Subunit BCL11A) • SLC2A1 (Solute Carrier Family 2 Member 1) • SMAD3 (SMAD Family Member 3)
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    TP53 mutation • STK11 mutation • PBRM1 mutation • MTOR mutation • MDM2 mutation
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    Besremi (ropeginterferon alfa-2b-njft)
    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
    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)
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    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • NTRK fusion
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    Mekinist (trametinib) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
    2ms
    Multi-institutional registry study of the results of the Oncomine Dx Target Test for advanced thyroid cancer in Japan (ATA 2024)
    Objective: In 2022, the OncomineTM Dx Target Test (ODxTT) was approved in Japan as a companion diagnostic for selecting patients eligible for selpercatinib for advanced thyroid cancer, introducing a multigene test for thyroid cancer... A total of 571 patients were enrolled. There were 357 women (62.5%) and 214 men (37.5%) with a mean age of 65.9 ± 14.2 years. Four hundred and 18 (73.2%) were papillary carcinoma (PTC), 56 (9.8%) follicular carcinoma (FTC), 31 (5.4%) poorly differentiated carcinoma (PDTC), 38 (6.7%) anaplastic carcinoma (ATC), 21 (3.7%) medullary carcinoma (MTC), and 7 (1.2%) others.
    Clinical • Late-breaking abstract • Metastases
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • HRAS (Harvey rat sarcoma viral oncogene homolog)
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    KRAS mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • NTRK1 fusion • RET fusion • RET mutation • HRAS mutation
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    Oncomine™ Dx Target Test
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    Retevmo (selpercatinib)
    2ms
    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)
    |
    NTRK3 fusion • RET fusion • ALK fusion
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    FoundationOne® CDx • FoundationOne®RNA
    2ms
    Genomic signature for oligometastatic disease in non-small cell lung cancer patients with brain metastases. (PubMed, Front Endocrinol (Lausanne))
    Patients with this signature exhibited higher rates of early oligoprogression. External validation could lead to a biomarker that has the potential to direct local therapies in oligometastatic patients.
    Journal • Metastases
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    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • ARID1A (AT-rich interaction domain 1A) • JAK2 (Janus kinase 2) • CCNE1 (Cyclin E1) • MAP2K2 (Mitogen-activated protein kinase kinase 2)
    2ms
    Case Report: Misdiagnosis of a lipofibromatosis-like neural tumor of the dorsal skin as dermatofibrosarcoma protuberans. (PubMed, Front Surg)
    Histological and immunohistochemical detections aid in the differential diagnosis of LPF-NTs. Complete surgical resection is the preferred treatment for LPF-NTs.
    Journal
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    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CD34 (CD34 molecule)
    2ms
    Real-Life Experience with Entrectinib in Neurotrophic Tyrosine Receptor Kinase Fusion-Positive Solid Tumors: A Multicenter Retrospective Trial. (PubMed, Target Oncol)
    In this retrospective study, we aimed to obtain real-world data concerning the use of entrectinib in patients with solid tumors harboring NTRK fusion genes. Although our findings are partially similar to the results of clinical studies, prospective studies in larger patient groups with more diverse tumor types and different demographic characteristics are needed to confirm the findings.
    Retrospective data • Journal
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    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK (Neurotrophic receptor tyrosine kinase)
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    NTRK positive • NTRK fusion
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    Rozlytrek (entrectinib)
    2ms
    Recurrent CLTC::SYK fusions and CSF1R mutations in juvenile xanthogranuloma of soft tissue. (PubMed, Blood)
    Finally, a TPM3::NTRK1 fusion or MAP2K1 deletion were detected in 2 children with systemic JXG who experienced spontaneous disease regression. This study advances the molecular understanding of histiocytic neoplasms and may guide diagnostics and clinical management.
    Journal
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    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • CCND1 (Cyclin D1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CD163 (CD163 Molecule) • TPM3 (Tropomyosin 3) • MAPK1 (Mitogen-activated protein kinase 1) • SYK (Spleen tyrosine kinase) • CLTC (Clathrin Heavy Chain) • CSF1R (Colony stimulating factor 1 receptor) • MRC1 (Mannose Receptor C-Type 1)
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    BRAF V600E • BRAF V600 • NTRK1 fusion • TPM3-NTRK1 fusion • CCND1 expression • CSF1R fusion • PDGFRB fusion • PDGFRB mutation
    2ms
    Clinical Utility of Circulating Tumor DNA for Detecting Lung Cancer Mutations by Targeted Next-Generation Sequencing With Insufficient Tumor Samples. (PubMed, J Clin Lab Anal)
    Identifying ctDNA mutations by targeted sequencing in plasma is feasible, showing the clinical value of ctDNA-targeted sequencing in NSCLC patients when tumor tissue sampling is insufficient or even impossible.
    Journal • Next-generation sequencing • Circulating tumor DNA
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TYK2 (Tyrosine Kinase 2)
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    TP53 mutation • EGFR mutation • BRAF mutation • ROS1 mutation
    2ms
    AB055. Infantile high-grade glioma (IHG)-a case series of Hong Kong experience. (PubMed, Chin Clin Oncol)
    Infantile high-grade glioma should be regarded as a unique tumor entity and a multidisciplinary approach is paramount in improving survival for this group of patients.
    Retrospective data • Journal
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    ALK (Anaplastic lymphoma kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase) • HMBOX1 (Homeobox Containing 1)
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    NTRK1 fusion • NTRK3 fusion • ALK fusion • ETV6-NTRK3 fusion • ROS1 fusion • ALK-ROS1 fusion • TPR-NTRK1 fusion • NTRK fusion
    2ms
    NTRK-rearranged spindle cell neoplasms – report of two cases with divergent morphology (ECP 2024)
    Identifying patients with NTRK gene fusions is crucial, as they could benefit from targeted therapy using TRK inhibitors. This requires a detailed description of emerging entities like NTRK-RSCNs because testing for NTRK rearrangement is not routinely performed. In two cases, we report a spectrum of histological grades, including a high-grade phenotype.
    Clinical
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    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CD34 (CD34 molecule) • LMNA (Lamin A/C) • SOX10 (SRY-Box 10) • PRAME (Preferentially Expressed Antigen In Melanoma) • NTRK (Neurotrophic receptor tyrosine kinase) • STAT6 (Signal transducer and activator of transcription 6) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
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    NTRK1 fusion • LMNA-NTRK1 fusion • NTRK fusion
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    Archer® FusionPlex® Sarcoma kit
    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
    |
    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
    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
    Targeting NTRK1 Enhances Immune Checkpoint Inhibitor Efficacy in NTRK1 Wild-type Non-Small Cell Lung Cancer. (PubMed, Cancer Res)
    Notably, suppression of the NTRK1 pathway by knockdown or Entrectinib treatment significantly enhanced ICI efficacy in mouse NSCLC models...RNA sequencing revealed that suppression of NTRK1 signaling in tumor cells increased complement C3 expression, which enhanced the recruitment of T cells and myeloid cells and stimulated M1-like macrophage polarization in the tumor. Together, this study demonstrates a role for NTRK1 signaling in regulating crosstalk between tumor cells and immune cells in the tumor microenvironment and provides a potential therapeutic approach to overcomes immunotherapy resistance in NTRK1 wild-type NSCLC patients.
    Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • NTRK (Neurotrophic receptor tyrosine kinase)
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    Rozlytrek (entrectinib)
    2ms
    DNA hypermethylation of tumor suppressor genes TWIST1, GATA4, MUS81 and NTRK1 in endometrial hyperplasia. (PubMed, Ceska Gynekol)
    Differences in DNA methylation among the groups were found in TWIST1, GATA4, MUS81, and NTRK1 genes (TWIST1: atypical hyperplasia 67.5%, benign hyperplasia 2.5%, normal endometrium 22.5%; P < 0.00001; GATA4: atypical hyperplasia 95%, benign hyperplasia 65%, normal endometrium 22.5%; P < 0.00001; MUS81: atypical hyperplasia 57.5%, benign hyperplasia 22.5%, normal endometrium 5%; P < 0.00001; NTRK1: atypical hyperplasia 65%, benign hyperplasia 27.5%, normal endometrium 10%; P < 0.00001). Higher methylation rates were observed for the tumor suppressor genes of TWIST1, GATA4, MUS81, and NTRK1 in samples with atypical endometrial hyperplasia compared to samples with normal endometrial tissue, and higher methylation rates were found in samples with atypical endometrial hyperplasia compared to samples of benign endometrial hyperplasia. DNA methylation of TWIST1, GATA4, MUS81, and NTRK1 is involved in the pathogenesis of atypical endometrial hyperplasia.
    Journal • Epigenetic controller
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    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • TWIST1 (Twist Family BHLH Transcription Factor 1) • MUS81 (MUS81 Structure-Specific Endonuclease Subunit)
    3ms
    Molecular Profiling of KIT/PDGFRA-Mutant and Wild-Type Gastrointestinal Stromal Tumors (GISTs) with Clinicopathological Correlation: An 18-Year Experience at a Tertiary Center in Kuwait. (PubMed, Cancers (Basel))
    KIT mutations were an adverse indicator of disease progression (p = 0.049), while wild-type status did not significantly impact progression (p = 0.934). The genetic landscape in this cohort mirrors that of global studies, but regional collaborations are needed to correlate outcomes with genetic variants.
    Journal • Stroma
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    KIT (KIT proto-oncogene, receptor tyrosine kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 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
    Molecular profiling of low-risk papillary thyroid carcinoma (mPTC) on active surveillance. (PubMed, J Clin Endocrinol Metab)
    The molecular profile of mPTC is like that of bigger PTC with the exception that none of them showed a TERT promoter mutation. The identification of the most common driver mutations, such as BRAF, RAS, or gene fusions, is not helpful for the early identification of mPTC that will show disease progression during follow-up in the AS program.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • TERT (Telomerase Reverse Transcriptase) • RAS (Rat Sarcoma Virus)
    3ms
    Afatinib as first-line treatment for advanced lung squamous cell carcinoma harboring uncommon EGFR G719C and S768I co-mutation: A case report and literature review. (PubMed, Heliyon)
    This case highlights the importance of genetic profiling in patients with LSCC. Although these patients have a low positive rate of EGFR mutations, searching for EGFR mutations in these patients might broaden their treatment options.
    Review • Journal • Metastases
    |
    EGFR (Epidermal growth factor receptor) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
    |
    Gilotrif (afatinib)
    3ms
    A Study to Evaluate the Efficacy and Safety of TL118 in Solid Tumors Patients (clinicaltrials.gov)
    P2, N=60, Recruiting, Teligene US | Not yet recruiting --> Recruiting | Trial completion date: Dec 2025 --> Apr 2026 | Initiation date: May 2024 --> Mar 2023 | Trial primary completion date: Dec 2025 --> Aug 2025
    Enrollment open • Trial completion date • Trial initiation date • 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)
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    TL118
    3ms
    Pyrazolo[1,5-a]pyrimidine as a Prominent Framework for Tropomyosin Receptor Kinase (Trk) Inhibitors-Synthetic Strategies and SAR Insights. (PubMed, Molecules)
    First-generation TRK inhibitors, i.e., Larotrectinib sulfate and Entrectinib, received clinical approval in 2018 and 2019, respectively...Fortunately, the second-generation Trk inhibitor Repotrectinib (TPX-0005) was approved by the FDA in November 2023, while Selitrectinib (Loxo-195) has provided an effective solution to this issue...This article focuses on a comprehensive review of chronological synthetic developments and the structure-activity relationships (SAR) of pyrazolo&lsqb;1,5-a]pyrimidine derivatives as Trk inhibitors. This article will also provide comprehensive knowledge and future directions to the researchers working in the field of medicinal chemistry by facilitating the structural modification of pyrazolo &lsqb;1,5-a]pyrimidine derivatives to synthesize more effective novel chemotherapeutics as TRK inhibitors.
    Review • Journal
    |
    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)
    |
    Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib) • selitrectinib (BAY 2731954)