Beside the aforementioned TKIs, multi-kinase TKIs also entered in the therapeutic armamentarium, among these regorafenib (Stivarga®; Bayer Pharma AG, Berlin, Germany), a compound active against several protein kinases related to angiogenesis (e.g., VEGFR-1/2/3), oncogenic pathways such as KIT, BRAF and RET, the metastatic process and immunosuppressive activity of the tumor microenvironment [140]. This evidence concerns the gene BRAF and neoplasm.