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    GENE:

    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)

    i
    Other names: NTRK2, TRKB, Neurotrophic tyrosine kinase, receptor, type 2
    2d
    A Phase 1/2 Study of D3S-002 as Monotherapy or Combination Therapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations (clinicaltrials.gov)
    P1/2, N=67, Recruiting, D3 Bio (Wuxi) Co., Ltd | Active, not recruiting --> Recruiting | Trial completion date: Apr 2028 --> Aug 2028 | Trial primary completion date: Apr 2028 --> Aug 2028
    Enrollment open • Trial completion date • Trial primary completion date • First-in-human
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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)
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    BRAF V600E • EGFR mutation • KRAS G12C • BRAF V600 • EGFR L858R • EGFR T790M • KRAS G12D • ALK rearrangement • MET exon 14 mutation • EGFR L861Q • ROS1 fusion • EGFR G719X • MET mutation • EGFR S768I • RET rearrangement • KRAS G12 • KRAS G12S • KRAS Q61
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    D3S-002 • elisrasib (D3S-001)
    6d
    Discovery of a sulfotyrosine-motif in the human TrkB extracellular domain required for agonist activation. (PubMed, bioRxiv)
    Our findings reveal unique features of TrkB, not present in the related neurotrophin receptors TrkA and TrkC, and suggest new directions to explore the role of sulfotyrosine in TrkB signalling and identify new TrkB-specific protein ligands. Investigation of the mechanism of action of TrkB agonist ZEB85 extends molecular understanding of TrkB activation.
    Journal
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    NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
    8d
    Unveiling the role of single versus repeated low-dose ketamine in attenuating doxorubicin-induced chemobrain and depression in rats: differential modulation of neuroinflammation, phosphorylated GLT-1, SERT, DAT and BDNF/TrkB signaling. (PubMed, Neuropharmacology)
    Collectively, these data suggest that KET, particularly when administered repeatedly at low doses, could be a promising adjunctive therapy to enhance quality of life for cancer patients undergoing DOX chemotherapy. However, because key intermediate nodes were not directly measured and KET-only control groups were not included, the proposed mechanistic cascade should be regarded as a hypothetical integrative model that warrants further validation.
    Preclinical • Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • TNFA (Tumor Necrosis Factor-Alpha)
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    doxorubicin hydrochloride
    9d
    Detecting Rare ALK Gene Fusions in Unclassified Spindle Cell Lung Tumors Using Anchored Multiplex PCR/Targeted RNA Next-Generation Sequencing. (PubMed, Genes Chromosomes Cancer)
    Our results support the incorporation of ALK immunohistochemistry as a screening tool and demonstrate the utility of anchored multiplex PCR-based RNA sequencing for the detection of therapeutically relevant fusions, particularly those with uncommon partners. This integrated approach may refine the diagnosis and support consideration of ALK-directed therapy in these rare tumors.
    Journal • Next-generation sequencing
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    ALK (Anaplastic lymphoma kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NRG1 (Neuregulin 1) • PPFIBP1 (PPFIA Binding Protein 1)
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    ALK positive • ALK rearrangement • ALK fusion • NRG1 fusion
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    Archer® FusionPlex® Sarcoma kit
    9d
    Discovery of YTB53, a Marine-Derived MNK-Active Anti-Acute Myeloid Leukemia Lead with Multi-Kinase Activity. (PubMed, J Med Chem)
    It also exhibited antiangiogenic effects and suppressed tumor growth in a xenograft model without overt toxicity. These findings support 31 as a promising multimechanistic lead for AML therapy, warranting further medicinal chemistry optimization to improve its pharmacokinetic properties and advance its development potential.
    Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    12d
    Rapid On-Site Next-Generation Sequencing: An Alternative to Single-Gene and Send-Out Testing in Non-Small Cell Lung Cancer and Colorectal Cancer in a Community Pathology Laboratory Setting. (PubMed, J Mol Diagn)
    In CRC, TAT was 4.1, 5.3, and 10.2; QNS 0%, 0%, 7.5%; detection 63.9%, 62.5%, and 57.1%. OPA provides faster TAT and lower QNS rates with comparable detection of actionable alterations, supporting its use for community-based molecular testing in NSCLC and CRC.
    Journal • 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) • MET (MET proto-oncogene, receptor tyrosine 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 mutation • KRAS G12C • BRAF mutation • HER-2 amplification • HER-2 mutation • RET fusion • MET exon 14 mutation • ALK fusion • ALK mutation • ROS1 fusion • KRAS G12
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    Oncomine Precision Assay
    14d
    STARTRK-2: Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions) (clinicaltrials.gov)
    P2, N=534, Active, not recruiting, Hoffmann-La Roche | Trial completion date: May 2026 --> Jun 2027 | Trial primary completion date: May 2026 --> Jun 2027
    Trial completion date • Trial primary completion date • Pan tumor
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    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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    ALK rearrangement • ROS1 rearrangement
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    Xalkori (crizotinib) • Rozlytrek (entrectinib)
    14d
    Differences Among Genomic Profiling Tests for Bone and Soft-Tissue Sarcomas in a Universal Health Insurance System. (PubMed, J Bone Joint Surg Am)
    In this cohort, the DNA+RNA-based panel showed a higher detection rate for TK fusions, although the panels were applied to different patient groups and the sensitivity and specificity could not be determined. Future studies evaluating different test types on the same tumor specimens are warranted to clarify whether the dual-sequencing approaches can improve the identification of actionable genetic events.
    Reimbursement • US reimbursement • 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) • EML4 (EMAP Like 4) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase) • RBPMS (RNA-binding protein with multiple splicing)
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    ALK fusion • NTRK fusion
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    FoundationOne® CDx • OncoGuide™ NCC Oncopanel System
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    Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
    20d
    Glioneuronal Tumour With Neurocytic Differentiation (GNTN): a Molecularly Defined Tumour Type Formerly Referred to as Extraventricular Neurocytoma. (PubMed, Neuropathol Appl Neurobiol)
    Collectively, these findings support the view that tumours previously labelled as EVN do not represent a direct counterpart of central neurocytoma but instead constitute a molecularly and epigenetically distinct glioneuronal tumour type. We propose the designation glioneuronal tumour with neurocytic differentiation (GNTN) to reflect its biological identity and to align the terminology with contemporary molecular neuropathology, and recommend DNA methylation profiling as an essential diagnostic criterion.
    Journal
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    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NF1 (Neurofibromin 1) • TACC1 (Transforming Acidic Coiled-Coil Containing Protein 1) • OLIG2 (Oligodendrocyte Transcription Factor 2)
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    PIK3CA mutation
    21d
    Detection of NTRK gene fusions in sarcomas: a comparative study of Pan-TRK immunohistochemistry, FISH, and RNA-Based NGS. (PubMed, Pathologica)
    FISH may represent a useful intermediate diagnostic tool when NGS is unavailable but requires cautious interpretation particularly in cases with atypical or isolated signals. NGS-based molecular confirmation remains essential for the definitive identification of NTRK fusions.
    Clinical • Retrospective data • Journal • Next-generation sequencing
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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) • BCOR (BCL6 Corepressor) • EWSR1 (EWS RNA Binding Protein 1) • NTRK (Neurotrophic receptor tyrosine kinase) • NACC2 (NACC Family Member 2)
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    NTRK positive • NTRK fusion
    21d
    Repotrectinib Post-Marketing Surveillance in Korean Patients With ROS1-Positive Non-Small Cell Lung Cancer (NSCLC) or Solid Tumors Harboring a Neurotrophic Tyrosine Receptor Kinase (NTRK) Gene Fusion (clinicaltrials.gov)
    P=N/A, N=10, Not yet recruiting, Bristol-Myers Squibb
    New trial
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    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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    ROS1 fusion • ROS1 positive
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    Augtyro (repotrectinib)
    24d
    Capmatinib targeted therapy in MET-fusion driven radiation induced glioma. (PubMed, Front Oncol)
    We review the characteristics of MET-altered pediatric high-grade glioma using the Open Pediatric Brain Tumor Atlas (Open PBTA) and published series, which suggests that MET fusions may be enriched in RIGs. Our two cases highlight the promising CNS penetration and on-target activity of capmatinib in MET-altered glioma; however, the development of rapid resistance emphasizes the pressing need to develop combination and/or new therapies for RIG.
    Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
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    Tabrecta (capmatinib)