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Editorial

  • Marilyn M. Li
    Correspondence
    Corresponding author.
    Affiliations
    Division of Oncology and Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Department of Pathology and Laboratory Medicine, Department of Pediatrics and Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
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  • Alexander Drilon
    Affiliations
    Early Drug Development Service, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA
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  • Theodore W. Laetsch
    Affiliations
    Division of Oncology and Center for Childhood Cancer Research, Children’s Hospital of Philadelphia and Department of Pediatrics and Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
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      The neurotrophic tyrosine receptor kinases (TRK) are membrane-bound receptors that regulate the growth, differentiation, and programmed cell death of neurons in the peripheral and central nervous systems. The TRK family includes TRKA (encoded by NTRK1), TRKB (encoded by NTRK2), and TRKC (encoded by NTRK3) proteins. Each TRK protein contains an extracellular ligand-binding domain, a transmembrane domain, and an intracellular tyrosine kinase domain [
      • Cunningham ME
      • Greene LA.
      A function-structure model for NGF-activated TRK.
      ]. Chimeric NTRK fusions are generally caused by chromosomal rearrangements resulting in the fusion of a 5’-partner gene with a 3’ NTRK gene that retains the entire tyrosine kinase domain. These NTRK fusions encode oncogenic proteins that constitutively activate signaling pathways, such as the Ras-mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and the phosphoinositide-3-kinase (PI3K)/AKT pathway, leading to the augmentation of cell migration and proliferation, as well as reduced programmed cell death.
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