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    GENE:

    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)

    i
    Other names: NTRK2, TRKB, Neurotrophic tyrosine kinase, receptor, type 2
    3d
    Detection and Significance of Molecular Markers in Immunotherapy and Targeted Therapy of Colorectal Cancer in Tibet (PubMed, Zhongguo Yi Xue Ke Xue Yuan Xue Bao)
    Results The 64 patients with colorectal cancer were at a male-to-female ratio of 1.21∶1,with the mean age of (56.59±13.27) years.The tumors were located in the colon in 46(71.88%) patients and in the rectum in 18(28.12%) patients.Sixty(93.75%) patients presented adenocarcinoma,and 4(6.25%) patients presented other types of tumors.The patients in T1/T2 and T3/T4 phases accounted for 17.19%(n=11) and 82.81%(n=53),respectively.Lymph node metastasis occurred in 24(37.50%) patients.The immunohistochemical staining results showed partially down-regulated or absent expression of SMARCA4 in 1(1.56%) patient,positive BRAF expression in 4(6.25%) patients,and mutant expression of P53 in 35(54.69%) patients.The PD-1-expressing tumor associated immune cell was proportion score<10% in 45(70.31%) patients and≥10% in 19(29.69%) patients.The PD-L1 combined positive score was<10 in 52(81.25%) patients and≥10 in 12(18.75%) patients.The gene fusion of NTRK1,NTRK2,and NTRK3 was negative in all the patients,and BRAF V600E gene mutation was positive in 4(6.25%) patients.The SMARCA4 gene alteration was not detected in the patient with partial expression missing of SMARCA4.The PD-L1 combine positive score was correlated with the deficient mismatch repair(dMMR)/microsatellite instability-high (MSI-H) and the PD-1 expression (χ2=10.223,P=0.001;χ2=11.979,P=0.001). Conclusions The down-regulated or absent SMARCA4 expression and NTRK gene fusion are rare in the patients with colorectal cancer in Tibet.A few patients present BRAF V600E gene mutations,and Pan-TRK and BRAF expression can be used for the primary screening of NTRK gene fusion and BRAF gene mutation.The patients with dMMR/MSI-H are prone to high expression of PD-L1 and expected to benefit from immunotherapy.No significant correlation exists between P53 mutation and PD-L1 expression.The high expression of PD-1 is positively correlated with the high expression of PD-L1.
    Journal • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • PD-1 (Programmed cell death 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • NTRK (Neurotrophic receptor tyrosine kinase) • SMARCD3 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily D, Member 3)
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    TP53 mutation • BRAF V600E • MSI-H/dMMR • PD-L1 overexpression • BRAF V600 • NTRK1 fusion • NTRK2 fusion • PD-1 expression • TP53 expression • BRAF positive • TP53 mutation + PD-L1 expression • NTRK expression • NTRK fusion
    5d
    Identification of potential targetable genes in papillary, follicular, and anaplastic thyroid carcinoma using bioinformatics analysis. (PubMed, Endocrine)
    The findings unravel potential biomarkers and therapeutic targets of thyroid carcinomas.
    Journal • IO biomarker
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    BCL2 (B-cell CLL/lymphoma 2) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • LYVE1 (Lymphatic vessel endothelial hyaluronan receptor 1) • PCLO (Piccolo Presynaptic Cytomatrix Protein)
    10d
    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
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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) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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    NTRK1 fusion • LMNA-NTRK1 fusion • NTRK1 mutation • NTRK fusion
    10d
    LncRNA RPL22P1-201 affects prostate cancer cell proliferation, cell cycle, and sensitivity to docetaxel by regulating miR-216b-5p expression (PubMed, Zhonghua Nan Ke Xue)
    RPL22P1-201 is highly expressed in prostate cancer, and silencing RPL22P1-201 inhibits prostate cancer PC3 cell proliferation and cell cycle by increasing miR-216b-5p expression, and enhances PC3 cell sensitivity to docetaxel.
    Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3)
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    CDK6 expression
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    docetaxel
    15d
    LightWAY: Intensive Weight Loss Intervention Versus Usual Care for Adults With Severe and Complex Obesity (clinicaltrials.gov)
    P=N/A, N=600, Recruiting, Carsten Dirksen | Not yet recruiting --> Recruiting
    Enrollment open
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • BDNF (Brain Derived Neurotrophic Factor) • CRP (C-reactive protein) • PCSK1 (Proprotein Convertase Subtilisin/Kexin Type 1)
    16d
    Agnostic Administration of Targeted Anticancer Drugs: Looking for a Balance between Hype and Caution. (PubMed, Int J Mol Sci)
    Several agnostic drug-target matches have already been approved for clinical use, e.g., immune therapy for tumors with microsatellite instability (MSI) and/or high tumor mutation burden (TMB), NTRK1-3 and RET inhibitors for cancers carrying rearrangements in these kinases, and dabrafenib plus trametinib for BRAF V600E mutated malignancies. The existing format of data dissemination may not be optimal for agnostic cancer medicine, as conventional scientific journals are understandably biased towards the publication of positive findings and usually discourage the submission of case reports. Despite all the limitations and concerns, histology-independent drug-target matching is certainly feasible and, therefore, will be increasingly utilized in the future.
    Review • Journal • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • 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) • HRD (Homologous Recombination Deficiency)
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    PD-L1 expression • BRAF V600E • TMB-H • HER-2 overexpression • HER-2 amplification • BRAF V600 • HRD • RET mutation • ALK translocation • NTRK1 mutation • HER-2 amplification + PD-L1 expression
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    Mekinist (trametinib) • Tafinlar (dabrafenib)
    20d
    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
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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) • 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)
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    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
    20d
    Acquired NF2 mutation confers resistance to TRK inhibition in an ex vivo LMNA::NTRK1-rearranged soft-tissue sarcoma cell model. (PubMed, J Pathol)
    Drug synergy was seen using trametinib and rapamycin in combination with entrectinib.
    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) • NF2 (Neurofibromin 2) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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    NF2 mutation • NTRK fusion
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    Mekinist (trametinib) • Rozlytrek (entrectinib) • sirolimus
    21d
    Intensive Weight Loss Intervention Versus Bariatric Surgery for Adults With Severe and Complex Obesity: the LightBAR Randomised Trial (clinicaltrials.gov)
    P=N/A, N=500, Recruiting, Carsten Dirksen | Not yet recruiting --> Recruiting
    Enrollment open • Surgery • Bariatric surgery
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • BDNF (Brain Derived Neurotrophic Factor) • CRP (C-reactive protein) • PCSK1 (Proprotein Convertase Subtilisin/Kexin Type 1)
    23d
    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
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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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    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion
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    TL118
    24d
    TNF receptor 2 knockout mouse had reduced lung cancer growth and schizophrenia-like behavior through a decrease in TrkB-dependent BDNF level. (PubMed, Arch Pharm Res)
    However, the addition of BDNF (100 ng/ml) into TNFR2 siRNA transfected A549 lung cancer cells recovered cell growth and the expression of TrkB. These results suggest that TNFR2 could be an important factor in mediating the comorbidity between lung tumor growth and SCZ development through increased TrkB-dependent BDNF levels.
    Preclinical • Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • TNFA (Tumor Necrosis Factor-Alpha) • BDNF (Brain Derived Neurotrophic Factor)
    26d
    ETV6-NTRK2 Fusion in a Patient With Metastatic Pulmonary Atypical Carcinoid Successfully Treated With Entrectinib: A Case Report and Review of the Literature. (PubMed, Clin Lung Cancer)
    After pursuing other alternative treatments, including chemotherapy (ie, carboplatin, etoposide, capecitabine, temozolomide, and paclitaxel), everolimus, and atezolizumab, she returned with significant progression, including innumerable subcutaneous nodules, left pleura metastasis, multiple bone metastases, and brain metastases. To date, she has maintained sustained benefit for at least 1 year from initiation of entrectinib. Here, we present the first case of a female patient with metastatic AC harboring the ETV6-NTRK2 fusion, and successfully treated with entrectinib, providing evidence for the application of entrectinib in patients with NTRK-positive AC, and underscoring the critical role of molecular profiling for such cases.
    Review • Journal • PD(L)-1 Biomarker • Metastases
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6) • SSTR (Somatostatin Receptor) • NTRK (Neurotrophic receptor tyrosine kinase)
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    NTRK2 fusion • ETV6-NTRK2 fusion • NTRK positive • SSTR Expression
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    Tecentriq (atezolizumab) • carboplatin • Rozlytrek (entrectinib) • paclitaxel • everolimus • temozolomide • capecitabine • etoposide IV
    1m
    Glioblastoma, IDH-Wildtype With Epithelioid Morphology and a BCR::NTRK2 Fusion. (PubMed, Int J Surg Pathol)
    Recent approval of the TRK inhibitor larotrectinib by the Food and Drug Administration (FDA) has brought interest in the study and recognition of NTRK fusions in multiple types of tumors. Trials that assess the response to this drug in cancers carrying NTRK fusions have yielded favorable results. We discuss a rare presentation of an adult-type GBM with epithelioid morphology and a BCR::NTRK2 gene fusion.
    Journal
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    BRAF (B-raf proto-oncogene) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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    BRAF V600E • BRAF V600 • NTRK2 fusion • IDH wild-type • NTRK fusion
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    Vitrakvi (larotrectinib)
    1m
    A recurrent NTRK1 tyrosine kinase domain mutation pair is characteristic in a subset of dedifferentiated liposarcomas. (PubMed, Eur J Cancer)
    We detected (de novo/somatic) missense mutation variants in cis position of the NTRK1 gene in a subset of DDLPS indicating modifying mutations that may contribute to tumorigenesis in a subset of DDLPS. These variants beget resistance to TRK inhibitors indicating an interesting biomarker for other studies with TRK inhibitors.
    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 mutation • NTRK fusion
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    Vitrakvi (larotrectinib) • selitrectinib (BAY 2731954)
    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
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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) • STRN (Striatin) • TPM3 (Tropomyosin 3) • CD34 (CD34 molecule) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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    NTRK1 fusion • NTRK2 fusion • NTRK expression
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    Vitrakvi (larotrectinib)
    1m
    Resveratrol prevents cognitive deficits induced by sleep deprivation via modulating sirtuin 1 associated pathways in the hippocampus. (PubMed, J Biochem Mol Toxicol)
    We found that resveratrol significantly reversed sleep deprivation-induced learning and memory impairment, elevated interleukin-1β, interleukin-6, and tumor necrosis factor-α levels, and decreased brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin levels by activating the Sirt1/miR-134 pathway. In conclusion, resveratrol is a promising agent for preventing sleep deprivation-induced cognitive dysfunction by reducing pro-inflammatory cytokines and improving synaptic function via the Sirt1/miR-134 pathway.
    Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL1B (Interleukin 1, beta) • SYP (Synaptophysin) • BDNF (Brain Derived Neurotrophic Factor) • MIR134 (MicroRNA 134)
    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
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    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6)
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    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion
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    Vitrakvi (larotrectinib)
    1m
    Development and Application of Comprehensive Intervention Techniques for Adolescent Depression (clinicaltrials.gov)
    P=N/A, N=100, Recruiting, First Affiliated Hospital of Zhejiang University | N=400 --> 100
    Enrollment change
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • BDNF (Brain Derived Neurotrophic Factor)
    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
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    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)
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    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
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    Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Rozlytrek (entrectinib) • Alecensa (alectinib) • Cotellic (cobimetinib) • Gavreto (pralsetinib) • divarasib (RG6330)
    1m
    Intensive Weight Loss Intervention Versus Usual Care for Adults With Obesity (clinicaltrials.gov)
    P=N/A, N=400, Not yet recruiting, Carsten Dirksen
    New trial
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • BDNF (Brain Derived Neurotrophic Factor) • CRP (C-reactive protein) • PCSK1 (Proprotein Convertase Subtilisin/Kexin Type 1)
    1m
    LightWAY: Intensive Weight Loss Intervention Versus Usual Care for Adults With Severe and Complex Obesity (clinicaltrials.gov)
    P=N/A, N=600, Not yet recruiting, Carsten Dirksen
    New trial
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • BDNF (Brain Derived Neurotrophic Factor) • CRP (C-reactive protein) • PCSK1 (Proprotein Convertase Subtilisin/Kexin Type 1)
    1m
    The Impact of Prior Single-Gene Testing on Comprehensive Genomic Profiling Results for Patients with Non-Small Cell Lung Cancer. (PubMed, Oncol Ther)
    For patients with NSCLC, initial use of SGT increases subsequent CGP test cancellations, turnaround time, and the likelihood of incomplete molecular profiling for guideline-recommended biomarkers due to tissue insufficiency.
    Journal • PD(L)-1 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) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
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    KRAS G12C • MET exon 14 mutation • KRAS G12
    2ms
    Novel CAR-T cells targeting TRKB for the treatment of solid cancer. (PubMed, Apoptosis)
    We also performed in vivo studies to show that NTF4-CAR T cells have a better potential to inhibit the tumor growth of hepatocellular carcinoma xenografts in mice, compared with BDNF-CAR T cells. Taken together, our findings suggest that CAR-T targeting TRKB may be a promising approach for developing novel therapies to treat solid cancers.
    Journal • CAR T-Cell Therapy
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • BDNF (Brain Derived Neurotrophic Factor)
    2ms
    TROP-2, NECTIN-4 and predictive biomarkers in sarcomatoid and rhabdoid bladder urothelial carcinoma. (PubMed, Pathologica)
    Different combinations of other positive biomarkers may help the choice of medical therapies. Overall, these findings have important clinical implications for targeted therapy for BUC.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • FGFR2 (Fibroblast 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) • NECTIN4 (Nectin Cell Adhesion Molecule 4) • NTRK (Neurotrophic receptor tyrosine kinase) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)
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    HER-2 amplification • HER-2 expression • NECTIN4 expression
    2ms
    Targeting the NTSR2/TrkB oncogenic pathway in chronic lymphocytic leukemia. (PubMed, Sci Rep)
    It demonstrated a cytotoxic effect both in vitro on the MEC-1 cell line and ex vivo on a cohort of 30 CLL patients. Altogether, these results underline the therapeutic potential of the NTSR2/TRKB protein complex as a target in CLL and open new perspectives for the development of targeted therapies.
    Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
    2ms
    Nicotine downregulates miR-375-3p via neurotrophic tyrosine receptor kinase 2 to enhance the malignant behaviors of laryngopharyngeal squamous epithelial cells. (PubMed, Ecotoxicol Environ Saf)
    Thus, this study uncovers a novel nicotine-induced mechanism involving miR-375-3p-mediated NTRK2 targeting, which promotes HNSCC metastasis. These findings have implications for improving the prognosis of patients with HNSCC, especially in smokers.
    Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • MIR375 (MicroRNA 375)
    2ms
    Identification of FLRT2 as a key prognostic gene through a comprehensive analysis of TMB and IRGPs in BLCA patients. (PubMed, Front Oncol)
    This study not only presents a novel prognostic marker but also carves out potential avenues for immunotherapy and targeted therapeutic strategies in BLCA. By demystifying the profound impact of immune-related genes and the tumor immune environment, this study augments the comprehension and prognostic management of bladder cancer.
    Journal • Tumor mutational burden • IO biomarker
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    TMB (Tumor Mutational Burden) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • PRSS3 (Serine Protease 3) • PRSS1 (Serine Protease 1) • CYTL1 (Cytokine Like 1)
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    TMB-L
    2ms
    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
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    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)
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    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
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    Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Rozlytrek (entrectinib) • Alecensa (alectinib) • Cotellic (cobimetinib) • Gavreto (pralsetinib) • divarasib (RG6330)
    2ms
    SYNERGY-AI: Artificial Intelligence Based Precision Oncology Clinical Trial Matching and Registry (clinicaltrials.gov)
    P=N/A, N=50000, Recruiting, Massive Bio, Inc. | Trial completion date: Jun 2025 --> Jun 2027 | Trial primary completion date: Dec 2024 --> Dec 2026
    Trial completion date • Trial primary completion date
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • HRAS (Harvey rat sarcoma viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • CLDN18 (Claudin 18) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • JAK2 (Janus kinase 2) • NRG1 (Neuregulin 1) • POLE (DNA Polymerase Epsilon) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PD-1 (Programmed cell death 1) • CCND1 (Cyclin D1) • MCL1 (Myeloid cell leukemia 1) • KDR (Kinase insert domain receptor) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • VEGFA (Vascular endothelial growth factor A) • BCL6 (B-cell CLL/lymphoma 6) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • PTCH1 (Patched 1) • FGFR4 (Fibroblast growth factor receptor 4) • MSH6 (MutS homolog 6) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • WT1 (WT1 Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • TSC2 (TSC complex subunit 2) • CHEK2 (Checkpoint kinase 2) • PD-L2 (Programmed Cell Death 1 Ligand 2) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • JAK1 (Janus Kinase 1) • FANCA (FA Complementation Group A) • TSC1 (TSC complex subunit 1) • MDM4 (The mouse double minute 4) • POLD1 (DNA Polymerase Delta 1) • CDK6 (Cyclin-dependent kinase 6) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • AURKA (Aurora kinase A) • JAK3 (Janus Kinase 3) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • CHEK1 (Checkpoint kinase 1) • GATA6 (GATA Binding Protein 6) • MSH3 (MutS Homolog 3) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • GNAS (GNAS Complex Locus) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3) • CSF1R (Colony stimulating factor 1 receptor) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • HDAC1 (Histone Deacetylase 1) • PRDM1 (PR/SET Domain 1) • ZNF217 (Zinc Finger Protein 217) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • GATA3 (GATA binding protein 3) • PARP2 (Poly(ADP-Ribose) Polymerase 2) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A) • ACVR1B (Activin A Receptor Type 1B) • ZNF703 (Zinc Finger Protein 703)
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    HER-2 mutation • BAP1 mutation • AKT1 mutation • FGFR3 fusion • JAK3 mutation
    2ms
    Differential expression of TRKB tyrosine kinase in the two histological types of parotid salivary duct carcinoma with cancer aggressiveness. (PubMed, Oral Oncol)
    Here, immunohistochemical and clinicopathological analyses showed that TRKB was highly expressed in SDC cells, particularly de novo SDC cells, and was significantly associated with poor survival and highly malignant phenotypes, including intra-NI and vascular invasion. Collectively, these data show that TRKB expression is significantly elevated in PGC, particularly in de novo SDC, and can be one of the biomarkers of their aggressiveness.
    Journal
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
    2ms
    Intensive Weight Loss Intervention Versus Bariatric Surgery for Adults With Severe and Complex Obesity: the LightBAR Randomised Trial (clinicaltrials.gov)
    P=N/A, N=500, Not yet recruiting, Carsten Dirksen
    New trial • Surgery • Bariatric surgery
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • BDNF (Brain Derived Neurotrophic Factor) • CRP (C-reactive protein) • PCSK1 (Proprotein Convertase Subtilisin/Kexin Type 1)
    2ms
    Building Resilience at Schools: Emotional and Biological Assessment and Treatment of Traumatic Stress (clinicaltrials.gov)
    P=N/A, N=80800, Recruiting, Stanford University | Not yet recruiting --> Recruiting
    Enrollment open
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    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • CD14 (CD14 Molecule) • IGFBP2 (Insulin-like growth factor binding protein 2) • CDK14 (Cyclin Dependent Kinase 14) • HNRNPH1 (Heterogeneous Nuclear Ribonucleoprotein H1) • WTAP (WT1 Associated Protein) • SLC1A3 (Solute Carrier Family 1 Member 3)
    2ms
    Gene expression profiling on CML patients with Philadelphia translocation. (PubMed, Eur Rev Med Pharmacol Sci)
    The results demonstrate a correlation between signaling pathways and the development of treatment resistance in patients with CML. These pathways exhibited enhanced efficacy in transmitting signals downstream of the TKI target, BCR-ABL. Several target genes require additional validation in a more extensive cohort study to verify their correlation with TKI resistance. The present research highlights that many BCR-ABL-independent pathways may be correlated with resistance, thus enhancing the prospective therapy options for patients with CML.
    Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
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    NTRK expression
    2ms
    ASPYRE-Lung: Validation of a simple, fast, robust and novel method for multi-variant genomic analysis of actionable NSCLC variants in tissue (AACR 2024)
    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 analysis algorithm. ASPYRE-Lung has the potential to be transformative in facilitating access to rapid, actionable molecular profiling of tissue for patients with NSCLC.
    Genomic analysis • Omic analysis
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
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    MET exon 14 mutation
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    ASPYRE-Lung
    2ms
    Deciphering the genomic landscape of Chilean cancer: Unveiling driver pathway divergence, and novel germline and actionable somatic variants (AACR 2024)
    Overall, tumors have mutations mainly in TP53 (42.4%), PIK3CA (12.5%), KRAS (9.6%), PTEN (4.7%), BRCA1/2 (9%). Driver mutations were present in TP53 (42%), PIK3CA (16%), KRAS (10%), ERBB2 (7%), PTEN (7%), BRCA1/2 (8%), ATM (7%), among others. Accionable mutations were found primarily in PIK3CA (17%), KRAS (10%), ERBB2 (9%), and NTRK1/2/3 (4.8%).
    BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • NOTCH1 (Notch 1) • MSH2 (MutS Homolog 2) • CDH1 (Cadherin 1) • TSC2 (TSC complex subunit 2)
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    TP53 mutation • KRAS mutation • PIK3CA mutation • PTEN mutation • TSC2 mutation
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    MSK-IMPACT
    2ms
    ASPYRE-Lung addresses critical gaps in NGS-based biomarker testing: Robust variant calling from NGS QC fails (AACR 2024)
    Samples were tested by ASPYRE-Lung using an input of 20 ng DNA and 6 ng RNA, except for 5 patient samples that were run at lower inputs, ranging from 4.25 to 14 ng DNA.Key findings:•Of the 94 patient samples that failed NGS QC, 98% of samples (92/94) passed ASPYRE-Lung QC and could inform patient care.•In the 92 patient samples that passed ASPYRE-Lung QC, 47% (43/92) had a detectable variant identified by ASPYRE-Lung.•All 26 control samples that passed NGS QC also passed ASPYRE-Lung QC.•Of the 5 samples with 4.25 to 14 ng DNA inputs to ASPYRE-Lung, data were generated on 4/5 samples and 2/4 had a detectable variant.•ASPYRE-Lung has the potential to provide actionable clinical information on patient samples deemed to be of insufficient quantity for NGS testing.ASPYRE-Lung has a high success rate, is easily adoptable and cost effective making it suitable as a first-line testing option, or for samples that are either QNS or fail NGS QC, and can provide a large fraction of NSCLC patients with actionable biomarker information, with potentially smaller tissue requirements. ASPYRE-Lung genomic testing is transformative for cancer care management, and allows more patients with NSCLC to benefit from effective and better tolerated therapies.
    Late-breaking abstract • Biomarker testing • 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) • 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)
    |
    ASPYRE-Lung
    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
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    Rozlytrek (entrectinib)
    2ms
    2021 WHO Classification of Lung Cancer: Molecular Biology Research and Radiologic-Pathologic Correlation. (PubMed, Radiographics)
    Radiologists play a key role not only in evaluation of tumor and metastatic disease but also in identification of optimal biopsy targets.
    Journal • PD(L)-1 Biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • 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)
    |
    KRAS mutation • EGFR mutation • BRAF mutation • ALK fusion
    3ms
    Infiltrative Tumor Border is Associated with Poor Prognostic Factors in Basal-Like Breast Cancer (USCAP 2024)
    Breast cancers classified as basal-like by PAM50 comprise a histologically heterogeneous group of tumors. Tumors with infiltrating borders are much more likely to be associated with LVI and lymph node metastasis compared with pushing border tumors. Genes more highly expressed in tumors with infiltrative borders include a number of potential therapeutic targets, suggesting unique therapeutic strategies.
    BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • BRCA1 (Breast cancer 1, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • TOP2A (DNA topoisomerase 2-alpha)
    |
    BRCA1 expression • NTRK expression
    |
    Prosigna™ Breast Cancer Prognostic Gene Signature Assay • nCounter® Breast Cancer 360™ Panel
    3ms
    Neuroprotective mechanism of ribisin A on H2O2-induced PC12 cell injury model. (PubMed, Tissue Cell)
    Moreover, ribisin A significantly increased mitochondrial membrane potential (MMP) and inhibited apoptosis of PC12 cells. Meanwhile, ribisin A activated the phosphorylation of ERK1/2 and its downstream molecule CREB by upregulating the expression of Trk A and Trk B, the upstream molecules of the ERK signaling pathway.
    Journal
    |
    NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha)
    |
    IL6 expression
    3ms
    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)