RET and neoplasm: Regorafenib is a TKI affecting the vasculature and tumor microenvironment by targeting the specific kinase proteins (VEGFR1,2,3, PDGFR, FGFR, KIT, BRAF, and RET), which is a category 1 option recommended by the NCCN guidelines for the treatment of patients with recurrent/refractory or metastatic osteosarcoma.