Neurotrophic receptor tyrosine kinase 2 (NTRK2) (NTRK2)

Neurotrophic receptor tyrosine kinase 2 (NTRK2), commonly referred to as Tropomyosin receptor kinase B (TrkB), is a high-affinity cell surface receptor for brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) [2, 5]. It plays a fundamental role in the central and peripheral nervous systems by mediating signaling pathways, such as MAPK/ERK and PI3K/Akt, which are essential for neuronal survival, axonal growth, and synaptic plasticity [3, 7, 11]. In addition to its neurodevelopmental functions, NTRK2 is a critical regulator of energy balance; genetic deficiencies in this receptor are associated with severe hyperphagia and early-onset obesity [5, 6]. In oncology, chromosomal rearrangements involving the NTRK2 gene create oncogenic fusions that drive constitutive kinase activity and tumor growth in a variety of pediatric and adult cancers [11]. Consequently, NTRK2 has become a significant therapeutic target for pan-Trk inhibitors like larotrectinib and entrectinib, which provide tissue-agnostic efficacy in patients harboring these fusions [2, 11]. Research also continues into NTRK2 agonists as potential treatments for neurodegenerative and psychiatric disorders, though challenges remain regarding central nervous system safety and metabolic side effects [4, 6].

Other names

Tropomyosin receptor kinase BTrkBNeurotrophic receptor tyrosine kinase 2BDNF receptorBDNF/NT-3 growth factors receptorNeurotrophic tyrosine kinase receptor type 2GP145-TrkB

Small molecule inhibition of the tyrosine kinase domain to block oncogenic signaling in NTRK-fusion-positive cancers [11]; pharmacological activation of the receptor via agonists to promote neuronal survival and neuroplasticity in neurodegenerative models [4, 6].