Trk

TRK refers to the tropomyosin receptor kinase family of receptor tyrosine kinases. In humans, three members exist: NTRK1 (TrkA), NTRK2 (TrkB), and NTRK3 (TrkC). They function as high-affinity receptors for neurotrophins and play essential roles in the development and maintenance of the nervous system. NGF binds TrkA; BDNF and NT-4 bind TrkB; NT-3 primarily binds TrkC, leading to receptor activation and downstream signaling that supports neuronal survival, differentiation, and synaptic plasticity.

Structurally, TRK receptors have an extracellular ligand-binding domain containing immunoglobulin-like motifs, a single transmembrane region, and an intracellular tyrosine kinase domain. Ligand engagement induces dimerization and autophosphorylation, triggering signaling cascades such as MAPK/ERK, PI3K-AKT, and PLCγ.

Clinical significance: NTRK gene fusions produce constitutively active TRK fusion proteins that drive tumor growth across multiple cancer types. They are detected by methods including fluorescence in situ hybridization (FISH), RT-PCR, and next-generation sequencing (NGS). TRK inhibitors larotrectinib and entrectinib have demonstrated tumor-agnostic efficacy and are approved for NTRK fusion–positive cancers. Notable fusions include ETV6-NTRK3 in infantile fibrosarcoma and secretory breast carcinoma.

In research and clinical practice, TRK status informs diagnostic and therapeutic decisions, and ongoing work addresses resistance mechanisms and safety monitoring associated with TRK inhibitors.