TrkA, TrkB, and TrkC are receptor tyrosine kinases encoded by the *NTRK1*, *NTRK2*, and *NTRK3* genes, respectively. They belong to the tropomyosin receptor kinase (Trk) family and play critical roles in neuronal development, survival, and plasticity by binding neurotrophins: TrkA primarily interacts with nerve growth factor (NGF), TrkB with brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4), while TrkC binds neurotrophin-3 (NT-3). These receptors activate downstream signaling pathways, including MAPK, PI3K/AKT, and PLCγ, influencing cell differentiation, synaptic strength, and apoptosis regulation.
Antibodies targeting TrkA, TrkB, and TrkC are essential tools in neuroscience and oncology research. In cancer, *NTRK* gene fusions—resulting in constitutively active Trk fusion proteins—are oncogenic drivers in diverse tumors (e.g., sarcomas, gliomas, secretory carcinomas). Pan-Trk antibodies, which detect all three Trk isoforms, are widely used in immunohistochemistry (IHC) to screen for NTRK fusions, aiding in patient stratification for targeted therapies like larotrectinib or entrectinib. However, isoform-specific antibodies help distinguish individual Trk expression patterns, as normal neural tissues express Trk receptors at varying levels, complicating interpretation.
Trk antibodies also support mechanistic studies in neurodegenerative diseases, pain signaling, and neurodevelopmental disorders. Challenges include cross-reactivity with non-fusion Trk proteins and variability in antibody performance across tissue types. Validation using positive/negative controls and molecular confirmation (e.g., RNA sequencing) is critical for diagnostic accuracy. Overall, TrkA+B+C antibodies bridge translational research and precision oncology, enabling both biomarker discovery and therapeutic monitoring.