Clinically validated TRK inhibitors demonstrate durable, tumor−agnostic efficacy with acceptable safety in NTRK−fusion cancers, offering agents with which to pharmacologically interrogate neurotrophin−dependent circuits in osteosarcoma when accompanied by appropriate biomarker enrichment; pathology best−practice guidance underscores the need to complement pan−TRK immunohistochemistry with orthogonal molecular assays and, for pathway activity, phospho−specific readouts (91–93). The gene discussed is NTRK1; the disease is osteosarcoma.