Sorafenib, the first FDA-approved targeted therapy (SHARP Trial, Asia-Pacific Trial)283, paved the way for other TKIs such as lenvatinib for first-line treatment (REFLECT trial)284, regorafenib (RESORCE trial)285, cabozantinib (CELESTIAL trial)286 and the anti-VEGF antibody ramucirumab (REACH-2 trial).287 However, immune checkpoint inhibitors have opened a completely new chapter in HCC systemic therapy with significantly improved overall survival rates emerging as a promising approach. This evidence concerns the gene VEGFA and hepatocellular carcinoma.