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    BIOMARKER:

    NTRK1 fusion

    i
    Other names: NTRK1, MTC, TRK, TRKA, Neurotrophic tyrosine kinase, receptor, type 1
    Entrez ID:
    4914
    Related biomarkers:
    Expression
    Mutation
    Fusion
    Others
    Related tests:
    1d
    Prevalence and detection methodology for preliminary exploration of NTRK fusion in gastric cancer from a single-center retrospective cohort. (PubMed, Hum Pathol)
    FISH could complement NGS detection, particularly when NTRK fusion is detected by DNA sequencing. NTRK fusion in GC may not be limited to specific subtypes.
    Retrospective data • Journal
    |
    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) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • LMNA-NTRK1 fusion • NTRK1 mutation • NTRK fusion
    4d
    Predictors of radioiodine (RAI)-avidity restoration for NTRK fusion-positive RAI resistant metastatic thyroid cancers. (PubMed, Eur Thyroid J)
    Case Presentation and We report two cases with RAI-resistant lung metastases treated with larotrectinib: 83-year-old male presenting with an ETV6::NTRK3 fusion-positive tumor with the TERT promoter mutation c.-124C>T, and a 31-year-old female presenting with a TPR::NTRK1 fusion-positive tumor (and negative for TERT promoter mutation)...In contrast, the TERT-negative tumor exhibited successful I-131 reuptake with a TDS of -0.060. As observed for RAI-resistance associated with concurrent TERT and BRAF mutations, the co-occurrence of TERT mutations and NTRK fusions may also contribute to re-sensitization failure.
    Journal • Metastases
    |
    BRAF (B-raf proto-oncogene) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • TERT (Telomerase Reverse Transcriptase) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRAF mutation • NTRK1 fusion • NTRK3 fusion • RET fusion • TERT mutation • TERT promoter mutation • NTRK1 positive • NTRK3 positive • BRAF mutation + TERT −124C>T • NTRK positive • RET positive • TERT 124C>T • NTRK fusion
    |
    Vitrakvi (larotrectinib)
    7d
    An odd dancing couple. Non-small cell lung carcinoma with coexisting EGFR mutation and NTRK-1 translocation: A case report. (PubMed, Diagn Cytopathol)
    Moreover, so was the case with the concomitant expression of NTRK fusions and EGFR mutations. We present a case report of a patient with concomitant EGFR mutation and NTRK1 fusion.
    Journal
    |
    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) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    EGFR mutation • NTRK1 fusion • NTRK1 mutation • NTRK expression • NTRK fusion
    10d
    Estimating the Prognostic Value of the NTRK Fusion Biomarker for Comparative Effectiveness Research in The Netherlands. (PubMed, Mol Diagn Ther)
    NTRK+ patients may have an increased risk of death compared with NTRK- patients. When using historic control data to assess the comparative effectiveness of TRK inhibitors, the prognostic value of the NTRK fusion biomarker should therefore be accounted for.
    Journal • HEOR
    |
    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • NTRK fusion
    11d
    The Molecular Landscape of Gastric Cancers for Novel Targeted Therapies from Real-World Genomic Profiling. (PubMed, Target Oncol)
    Real-world datasets from clinical panel testing revealed the genomic landscape in gastric cancer by subgroup. These findings provide insights for the current therapeutic strategies and future development of treatments in gastric cancer.
    Journal • Real-world evidence • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • Real-world
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • CDH1 (Cadherin 1)
    |
    BRAF V600E • TMB-H • MSI-H/dMMR • KRAS G12C • HER-2 amplification • PIK3CA mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • MET amplification • MET mutation • KRAS G12
    15d
    A Study to Evaluate the Efficacy and Safety of TL118 in Solid Tumors Patients (clinicaltrials.gov)
    P2, N=60, Not yet recruiting, Teligene US | Initiation date: Jan 2024 --> May 2024
    Trial initiation date
    |
    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
    |
    TL118
    23d
    Post-therapy emergence of an NBN reversion mutation in a patient with pancreatic acinar cell carcinoma. (PubMed, NPJ Precis Oncol)
    Upon disease progression following 13 months of treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), genomic analysis of a metastatic liver biopsy revealed the emergence of a novel reversion mutation restoring the reading frame of NBN. The patient was treated with, but did not respond to, targeted treatment with a selective NTRK inhibitor. This case highlights the complex but highly actionable genomic landscape of PACC and underlines the value of genomic profiling of rare tumor types such as PACC.
    Journal
    |
    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • NBN mutation
    |
    5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium
    1m
    Primary NTRK-rearranged Spindle Cell Neoplasm of the Gastrointestinal Tract: A Clinicopathological and Molecular Analysis of 8 Cases. (PubMed, Am J Surg Pathol)
    One patient was succumbed to the disease at 12 months despite adjunctive treatment with TRK inhibitor larotrectinib after surgery...The final diagnosis relies on molecular assays. Patients with advanced disease may benefit from TRK inhibitor treatment.
    Journal
    |
    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • STRN (Striatin) • TPM3 (Tropomyosin 3) • CD34 (CD34 molecule) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • NTRK2 fusion • NTRK expression
    |
    Vitrakvi (larotrectinib)
    1m
    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: Mar 2024 --> Sep 2024 | Trial primary completion date: Mar 2024 --> Sep 2024
    Trial completion date • 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) • ETV6 (ETS Variant Transcription Factor 6)
    |
    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion
    |
    Vitrakvi (larotrectinib)
    1m
    NAUTIKA1: A Study of Multiple Therapies in Biomarker-Selected Patients With Resectable Stages IB-III Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=146, Recruiting, Genentech, Inc. | N=85 --> 146
    Enrollment change
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma 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)
    |
    PD-L1 expression • KRAS mutation • KRAS G12C • BRAF mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ALK fusion • RET mutation • ROS1 fusion • KRAS G12 • ALK-ROS1 fusion
    |
    Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Rozlytrek (entrectinib) • Alecensa (alectinib) • Cotellic (cobimetinib) • Gavreto (pralsetinib) • divarasib (RG6330)
    1m
    NAUTIKA1: A Study of Multiple Therapies in Biomarker-Selected Patients With Resectable Stages IB-III Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=85, Recruiting, Genentech, Inc. | Trial primary completion date: Mar 2024 --> Dec 2025
    Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma 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)
    |
    PD-L1 expression • KRAS mutation • KRAS G12C • BRAF mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ALK fusion • RET mutation • ROS1 fusion • KRAS G12 • ALK-ROS1 fusion
    |
    Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Rozlytrek (entrectinib) • Alecensa (alectinib) • Cotellic (cobimetinib) • Gavreto (pralsetinib) • divarasib (RG6330)
    1m
    Epithelioid cell histiocytoma associated with IRF2BP2::NTRK1 fusion. (PubMed, Pathology)
    No abstract available
    Journal
    |
    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
    |
    NTRK1 fusion
    2ms
    Real-World Clinical Performance of a DNA-Based Comprehensive Genomic Profiling Assay for Detecting Targetable Fusions in Nonsquamous NSCLC. (PubMed, Oncologist)
    A well-designed DNA CGP assay is capable of robust fusion detection and these fusion calls are reliable for informing clinical decision-making. While DNA CGP detects most driver fusions, the clinical impact of fusion detection is substantial for individual patients and exhaustive efforts, inclusive of additional RNA-based testing, should be considered when an oncogenic driver is not clearly identified.
    Real-world evidence • Journal • Real-world
    |
    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) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • FGFR2 fusion • ALK fusion • ROS1 fusion • FGFR3 fusion • ALK-ROS1 fusion
    |
    FoundationOne® CDx
    2ms
    STARTRK-NG: Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options (clinicaltrials.gov)
    P1/2, N=69, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Mar 2023 --> Jun 2025
    Trial primary completion date • Metastases
    |
    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 • ROS1 fusion
    |
    Rozlytrek (entrectinib)
    2ms
    A novel EML4-NTRK3 fusion in lung adenocarcinoma with dramatic response to entrectinib. (PubMed, J Cancer Res Ther)
    Despite the rare occurrence, these alterations have gained importance owing to approval of drugs like entrectinib and larotrectinib targeting the kinase domain of the gene. Detection of these rests on the use of conventional modalities like Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH); however, accurate characterization requires direct sequencing methods. We report an interesting case of an NTRK fusion-positive NSCLC, exhibiting good response to entrectinib.
    Journal
    |
    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • ETV6 (ETS Variant Transcription Factor 6) • SQSTM1 (Sequestosome 1) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • NTRK3 fusion • SQSTM1-NTRK1 fusion • EML4-NTRK3 fusion • NTRK positive • NTRK fusion
    |
    Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
    2ms
    Larotrectinib to Enhance RAI Avidity in Differentiated Thyroid Cancer (clinicaltrials.gov)
    P2, N=13, Recruiting, Children's Hospital of Philadelphia | Not yet recruiting --> Recruiting
    Enrollment open
    |
    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
    |
    Vitrakvi (larotrectinib)
    2ms
    Baseline ctDNA gene alterations as a biomarker of survival after panitumumab and chemotherapy in metastatic colorectal cancer. (PubMed, Nat Med)
    The phase 3 PARADIGM trial (n = 802) demonstrated longer overall survival with first-line anti-EGFR (panitumumab) versus antivascular endothelial growth factor (bevacizumab) plus modified FOLFOX6 in patients with RAS wild-type mCRC with left-sided primary tumors. Negative hyperselection using ctDNA may guide optimal treatment selection in patients with mCRC. ClinicalTrials.gov registrations: NCT02394834 and NCT02394795 .
    Journal • Circulating tumor DNA • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
    |
    HER-2 amplification • NTRK1 fusion • MET amplification • PTEN mutation • RAS wild-type • MET mutation • HER-2 amplification + MET amplification
    |
    Avastin (bevacizumab) • Vectibix (panitumumab) • oxaliplatin
    3ms
    Translation into Clinical Practice of the G1-G7 Molecular Subgroup Classification of Glioblastoma: Comprehensive Demographic and Molecular Pathway Profiling. (PubMed, Cancers (Basel))
    The correlations between the MAPK pathway G1-G7 subgroups and the PI3-kinase/PTEN, TERT, cell cycle G1 phase and p53 pathways defined characteristic subgroup pathway profiles amenable to personalized targeted therapy. This analysis validated the first all-inclusive molecular classification of glioblastoma, showed significant demographic and molecular differences between subgroups, and provided the first ethnic molecular comparison of glioblastoma.
    Journal • Tumor mutational burden
    |
    EGFR (Epidermal growth factor receptor) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NF1 (Neurofibromin 1) • LMNA (Lamin A/C) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)
    |
    EGFR mutation • NTRK1 fusion • NF1 mutation • ROS1 fusion • GOPC-ROS1 fusion • LMNA-NTRK1 fusion • NTRK1 overexpression
    3ms
    NAVIGATE: A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors (clinicaltrials.gov)
    P2, N=215, Active, not recruiting, Bayer | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    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
    |
    Vitrakvi (larotrectinib)
    3ms
    Cancer Molecular Screening and Therapeutics (MoST) Program Substudy Addendum 6 substudy 14-15: Larotrectinib (ACTRN12619001147178)
    P2, N=32, Active, not recruiting, The University of Sydney | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    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 • NTRK1 overexpression • NTRK expression
    |
    Vitrakvi (larotrectinib)
    3ms
    Selective TrkA Inhibitor VMD-928 to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma (clinicaltrials.gov)
    P1, N=74, Recruiting, VM Oncology, LLC | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025
    Trial completion date • Trial primary completion date
    |
    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
    |
    NTRK1 fusion • NTRK1 mutation • NTRK expression
    |
    VMD-928
    4ms
    ETV6::NTRK3 gene fusion in a patient with metastatic lung atypical carcinoid successfully treated with repotrectinib: A case report. (PubMed, Lung Cancer)
    To the best of our knowledge, we reported the first case demonstrating anti-tumor activity of repotrectinib in a patient with AC carring an ETV6-NTRK3 gene fusion, indicating that repotrectinib may be an efficient therapeutic option for tumors with NTRK gene rearrangements.
    Clinical • Observational data • Retrospective data • Review • Clinical Trial,Phase I • Clinical Trial,Phase II • Journal • Metastases
    |
    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) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • ETV6-NTRK3 fusion
    |
    everolimus • Augtyro (repotrectinib) • VC004
    4ms
    A Study of Repotrectinib in Combination With Chemotherapy in Children and Young Adults With Solid Tumor Cancer (clinicaltrials.gov)
    P1/2, N=50, Recruiting, Memorial Sloan Kettering Cancer Center
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    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 • ROS1 fusion
    |
    temozolomide • irinotecan • Augtyro (repotrectinib)
    4ms
    NTRK-rearranged spindle cell sarcoma of the uterine cervix with a novel NUMA1::NTRK1 fusion. (PubMed, Virchows Arch)
    The resulting fusion protein comprises the oligomerization domain of NUMA1, which is predicted to cause constant activation of the tyrosine kinase domain of NTRK1. The recognition and accurate diagnosis of these tumours are important due to the availability of potential targeted therapeutic options.
    Journal
    |
    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • NTRK fusion
    |
    FusionPlex® Pan Solid Tumor v2 panel
    4ms
    Spitz Tumors and Melanoma in the Genomic Age: A Retrospective Look at Ackerman's Conundrum. (PubMed, Cancers (Basel))
    A ternary classification Spitz nevus-Spitz melanocytoma-Spitz melanoma is more adherent to the real neoplastic pathway, but some cases with intermediate ambiguous features remain difficult to diagnose. A prognostic stratification of Spitz tumors, based on the morphologic and genomic characteristics, as a complement to the diagnosis, may contribute to better treatment plans for patients.
    Retrospective data • Review • Journal
    |
    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) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8)
    |
    BRAF mutation • NTRK1 fusion • NTRK2 fusion • ALK fusion • CDKN2A deletion • HRAS mutation • TERT mutation
    4ms
    Undifferentiated pleomorphic sarcoma of the pancreas with novel SARM1-NTRK1 gene fusion and associated pancreatitis, panniculitis, and polyarthritis syndrome. (PubMed, Pediatr Blood Cancer)
    No abstract available
    Journal
    |
    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
    |
    NTRK1 fusion
    4ms
    Fibroblastic orbital tumour with NTRK1 fusion transcript: when TRK inhibitors rescue surgery. (PubMed, Can J Ophthalmol)
    No abstract available
    Review • Journal • Surgery
    |
    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
    |
    NTRK1 fusion
    5ms
    Larotrectinib to Enhance RAI Avidity in Differentiated Thyroid Cancer (clinicaltrials.gov)
    P2, N=13, Not yet recruiting, Children's Hospital of Philadelphia | Initiation date: Nov 2023 --> Feb 2024
    Trial initiation 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
    |
    Vitrakvi (larotrectinib)
    5ms
    Sequential treatments with TRK inhibitors in a patient with NTRK fusion-positive sarcoma: A case report. (PubMed, Medicine (Baltimore))
    In the treatment of NTRK fusion-positive tumors, there are cases in which 2 approved first-generation TRK inhibitors can be used sequentially.
    Journal
    |
    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • NTRK positive • NTRK fusion
    |
    Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
    5ms
    BRAF variants and oncogenic fusions to define sporadic MMR-deficient colorectal cancer subtypes. (ASCO-GI 2024)
    In sporadic MMRd CRC, gene fusion-positive tumors exhibit an improved prognosis with similar molecular and treatment outcomes to BRAF-V600E-mut tumors. BRAF-V600E-wt/fusion-negative tumors are a unique sporadic MMRd subtype driven by alternative WNT-activation and potentially lower immunotherapy responses in small numbers of patients.
    IO biomarker
    |
    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • FGFR2 (Fibroblast growth factor receptor 2) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRAF V600E • MSI-H/dMMR • NTRK1 fusion • BRAF wild-type • FGFR2 fusion • ALK fusion
    |
    MSK-IMPACT
    5ms
    Detection of NTRK fusions by RNA-based nCounter is a feasible diagnostic methodology in a real-world scenario for non-small cell lung cancer assessment. (PubMed, Sci Rep)
    The concordance rate between IHC and RNA-based NGS was 33.4%, and between immunohistochemistry and nCounter was 40%. Our findings indicate that NTRK fusions in Brazilian NSCLC patients are relatively rare (1.3%), and RNA-based nCounter methodology is a suitable approach for NRTK fusion identification in small biopsies.
    Journal • Real-world evidence • Real-world
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • NTRK3 fusion • NTRK positive • NTRK fusion
    5ms
    A Misleading Case of NTRK-Rearranged Papillary Thyroid Carcinoma. (PubMed, Oncologist)
    Between August 2019 and August 2020, the patient received 2 ineffective lines of systemic therapy, including a first line of chemotherapy with cisplatin and pemetrexed, and a second line of immunotherapy with atezolizumab. After palliative partial thyroidectomy that confirmed the diagnosis of papillary thyroid carcinoma, in February 2021, the patient was enrolled in the STARTRK-2 GO40782 basket trial and received entrectinib, an oral pan-TRK inhibitor specifically targeting NTRK-rearranged tumors. After initially experiencing drug-related grade 2 anorexia, dysgeusia, and neurotoxicity and grade 3 asthenia, the dose was reduced, and an excellent and durable objective response was observed.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • TERT (Telomerase Reverse Transcriptase) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • TERT mutation • NTRK1 mutation
    |
    cisplatin • Tecentriq (atezolizumab) • Rozlytrek (entrectinib) • pemetrexed
    5ms
    Spitz tumor with RAF1 fusion: A report of 3 cases. (PubMed, Ann Diagn Pathol)
    Two cases were classified as Spitz nevus, while the remaining neoplasm was classified as Spitz melanoma at the time of the diagnosis, given 9p21 homozygous deletion and positive sentinel lymph node biopsy. We suggest that RAF1 fused melanocytic neoplasms can represent a novel subgroup of Spitz tumors, with a RAF1 fusion representing an oncogenic driver.
    Journal
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    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) • HRAS (Harvey rat sarcoma viral oncogene homolog) • BAP1 (BRCA1 Associated Protein 1) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8)
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    BRAF mutation • NTRK1 fusion • NTRK2 fusion • ALK fusion • HRAS mutation
    5ms
    Detection of Novel Tyrosine Kinase Fusion Genes as Potential Therapeutic Targets in Bone and Soft Tissue Sarcomas Using DNA/RNA-based Clinical Sequencing. (PubMed, Clin Orthop Relat Res)
    DNA- and RNA-based screening systems may be useful for detecting tyrosine kinase fusion genes in specific fusion-negative sarcomas and identifying key therapeutic targets, leading to possible breakthroughs in the treatment of bone and soft tissue sarcomas. Given that current DNA sequencing misses fusion genes, RNA-based screening systems should be widely considered as a worldwide test for sarcoma. If standard treatments such as chemotherapy are not effective, or even if the sarcoma is of bone, RNA sequencing should be considered to identify as many therapeutic targets as possible.
    Journal
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    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • KDR (Kinase insert domain receptor) • CDK4 (Cyclin-dependent kinase 4) • LMNA (Lamin A/C) • CLTC (Clathrin Heavy Chain) • NTRK (Neurotrophic receptor tyrosine kinase) • CEP290 (Centrosomal Protein 290) • FOXP2 (Forkhead Box P2)
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    NTRK1 fusion • NTRK3 fusion • ALK fusion • LMNA-NTRK1 fusion • NTRK3 positive • NTRK positive • NTRK fusion
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    TruSight Tumor 170 Assay
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    Vitrakvi (larotrectinib)
    5ms
    Larotrectinib for the Treatment of a Radiation-Induced Glioma with NTRK1 Gene Fusion in a Pediatric Patient (ASHP 2023)
    No abstract available
    Clinical
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    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
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    NTRK1 fusion
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    Vitrakvi (larotrectinib)
    5ms
    The Utility of Clinical Sequencing in the Diagnosis and Treatment of Soft Tissue Sarcomas; Real-World Database on Nationwide Database (AAOS 2024)
    Gounder showed thar CGP could lead to refinement or reassignment of 10.5% of diagnoses and 32% of the patients harbored potentially actionable alterations. In this study, 2.8% of patients were reclassified and the actionable gene mutations were found in 25% of the patients with sarcoma by the CGP. Although few patients could receive genotype-matched therapy, they could achieve relatively good control.
    Real-world evidence • Clinical • Tumor mutational burden • MSi-H Biomarker • MSi-H Companion diagnostic • Real-world
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    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • BCOR (BCL6 Corepressor) • EWSR1 (EWS RNA Binding Protein 1) • FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor) • NTRK (Neurotrophic receptor tyrosine kinase) • DUX4 (Double Homeobox 4)
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    TMB-H • MSI-H/dMMR • NTRK1 fusion • NTRK3 fusion • ALK fusion • ROS1 fusion • NTRK fusion
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    FoundationOne® CDx • FoundationOne® Liquid CDx • OncoGuide™ NCC Oncopanel System
    5ms
    Analysis of CD74 Occurrence in Oncogenic Fusion Proteins. (PubMed, Int J Mol Sci)
    Fusion proteins known to be oncogenic drivers, including those of CD74, are typically detected and targeted after standard chemotherapeutic plans fail and the disease relapses. The analysis reported herein provides insights into the early intervention of CD74 fusions and highlights the need for improved routine assessment methods so that targeted therapies can be applied while they are most effective.
    Review • Journal
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    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NRG1 (Neuregulin 1) • CD74 (CD74 Molecule) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • NRG2 (Neuregulin 2)
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    NTRK1 fusion • NRG1 fusion
    5ms
    Analytical Performance and Concordance with Next-Generation Sequencing of a Rapid, Multiplexed dPCR Panel for the Detection of DNA and RNA Biomarkers in Non-Small-Cell Lung Cancer. (PubMed, Diagnostics (Basel))
    The population prevalence-based coverage ranged from 89.2% to 100.0% across targets and exceeded 99.0% in aggregate. The assay demonstrated >97% concordance with respect to the comparator method.
    Journal • Next-generation sequencing • Discordant
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    ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • 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 • MET exon 14 mutation
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    FusionPlex® Dx • Oncomine Precision Assay
    6ms
    Using genetically-engineered mouse models of treatment-naïve and -experienced NTRK fusion-driven gliomas for pre-clinical trials of tyrosine kinase inhibitors (SNO 2023)
    These modifications altered the response to TKI treatment both in vitro and in vivo. Overall, these models serve as valuable tools for studying the biology of NTRK fusion tumors, their treatment response in a treatment-naïve or -experienced state, and the mechanisms underlying treatment resistance.
    Preclinical
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf 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) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NTRK (Neurotrophic receptor tyrosine kinase)
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    BRAF V600E • KRAS mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • KRAS G12D • KRAS G12 • BRAF V600E + KRAS G12D • NTRK fusion
    6ms
    Molecular profiling and actionable mutations in adult patients with IDH wild type gliomas and glioneuronal and neuronal tumors (SNO 2023)
    Three patients recurred after first-line therapy: 1 with BRAF mutated GBM, 1 with GBM harboring FGFR3-TACC3 fusion, and 1 with NTRK1 fusion positive glioneuronal tumor received specific BRAF/MEK inhibitor (dabrafenib/trametinib), FGFR inhibitor (pemigatinib), and NTRK inhibitor (larotrectinib), respectively. The incidence of actionable molecular alterations in IDH wt gliomas and glioneuronal/neuronal tumors was low. However, the use of targeted therapies may lead to significant impact on the outcome.
    Clinical
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • FGFR3 (Fibroblast growth factor receptor 3) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TACC3 (Transforming acidic coiled-coil containing protein 3) • NTRK (Neurotrophic receptor tyrosine kinase)
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    BRAF V600E • KRAS mutation • PIK3CA mutation • BRAF V600 • NTRK1 fusion • KIT mutation • FGFR3-TACC3 fusion • MET mutation • FGFR3 fusion • IDH wild-type • NTRK1 positive
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    Mekinist (trametinib) • Tafinlar (dabrafenib) • Vitrakvi (larotrectinib) • Pemazyre (pemigatinib)
    6ms
    TRIDENT-1: A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (clinicaltrials.gov)
    P1/2, N=500, Recruiting, Turning Point Therapeutics, Inc. | Trial completion date: Dec 2024 --> Feb 2028 | Trial primary completion date: Jun 2024 --> Feb 2028
    Trial completion date • Trial primary completion date • Metastases
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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)
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    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • ROS1 fusion
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    Augtyro (repotrectinib) • midazolam hydrochloride
    6ms
    Genomic Landscape of Malignant Phyllodes Tumors Identifies Subsets for Targeted Therapy (SABCS 2023)
    Additionally, one MPT sample harbored a pathogenic NTRK1 fusion (TPM4:NTRK1), and treatment with larotrectinib for over 16 months suggests a clinical response to therapy... Our study demonstrates the importance of employing next generation sequencing (NGS) in MPTs to detect actionable genomic alterations. To effectively analyze fusions, an NGS panel that include RNA sequencing is recommended, considering the occurrence of NTRK1 fusion reported herein. Although HER2 transcriptional expression was low, further investigations examining HER2 IHC in PTs are still necessary.
    Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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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) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • KMT2D (Lysine Methyltransferase 2D) • TPM4 (Tropomyosin 4)
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    PD-L1 expression • EGFR mutation • MSI-H/dMMR • BRAF mutation • HER-2 negative • PIK3CA mutation • NTRK1 fusion • HER-2 expression • NF1 mutation • KMT2D mutation
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    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
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    Vitrakvi (larotrectinib)