Neurotrophic Receptor Tyrosine Kinase Family (NTRK1, NTRK2, NTRK3) (NTRK Family (TRK Family))

The neurotrophic receptor tyrosine kinases TRKA, TRKB, and TRKC (encoded by NTRK1, NTRK2, and NTRK3) are single-pass transmembrane receptors in the TRK family responsible for mediating the effects of neurotrophins—specifically, nerve-growth factor (NGF, for TRKA), brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4, for TRKB), and neurotrophin-3 (NT-3, for TRKC). Ligand binding induces dimerization and autophosphorylation of these receptors, which triggers multiple downstream signaling cascades (RAS/MAPK, PI3K/AKT, PLCγ) essential for neuronal growth, differentiation, survival, and synaptic plasticity. Oncogenic NTRK gene fusions lead to constitutive kinase activation, bypassing the need for ligand stimulation and driving uncontrolled cellular proliferation; these fusions are seen in a variety of tumor types, often as early transformative events. Several highly selective TRK inhibitors have been developed for targeting NTRK fusion-positive solid tumors, making these genes and proteins key actionable therapeutic targets in precision oncology. Their expression and gene fusion status also serve as predictive biomarkers for response to TRK inhibitor treatment. Mutations, especially fusion of the 3′ region of NTRK genes with various partners, remain a major mechanism of tumorigenesis and therapeutic resistance. These receptors remain essential for normal neuronal health, so their inhibition can result in neurological side effects or developmental risks, particularly in pediatric populations.

Other names

TrkATRKAMTCGP145-TrkAp140-TrkAHSN2TrkBTRKBGP145-TrkBp145-TrkBTrkCTRKCGP145-TrkCp145-TrkCTRK receptorsNTRK receptorsTRK proteins

Selective inhibition of TRK tyrosine kinase activity, blocking downstream MAPK/ERK, PI3K/AKT, and PLCγ signaling pathways to suppress tumor cell proliferation and induce tumor regression