Class−selective TRK inhibition is directly testable: in orthotopic osteosarcoma models, larotrectinib suppressed NGF−driven MEK/ERK–MMP−2 signaling and reduced lung metastasis, providing a tumor−intrinsic and microenvironment−relevant mechanism that can be paired with immune readouts (72, 73). This evidence concerns the gene MMP2 and osteosarcoma.