Evidence has been accumulated with the real−world application of TRK inhibitors in fusion−positive cancers and anti−NGF biologics in bone pain, together with osteosarcoma specimens and functional models showing that NGF/BDNF signaling promotes invasion, angiogenesis, and immunosuppressive niches, while neuromodulatory agents may counter these programs. The gene discussed is BDNF; the disease is osteosarcoma.