Multikinase inhibitors (MKIs) have been the only first-line treatment for advanced
hepatocellular carcinoma (HCC) for more than a decade, until the approval of
immune checkpoint inhibitors (ICIs). Moreover, the combination regimen of
atezolizumab (anti-
programmed cell death protein ligand 1 antibody) plus
bevacizumab (anti-
vascular endothelial growth factor monoclonal antibody) has recently been demonstrated to have superior efficacy when compared with
sorafenib monotherapy. The remarkable efficacy has made this combination
therapy the new standard treatment for advanced HCC. In addition to MKIs, many other molecularly targeted
therapies are under investigation, some of which have shown promising results. Therefore, in the era of immuno-oncology, there is a significant rationale for testing the combinations of molecularly targeted
therapies and ICIs. Indeed, numerous preclinical and clinical studies have shown the synergic antitumor efficacy of such combinations. In this review, we aim to summarize the current knowledge on the combination of molecularly targeted
therapies and immune checkpoint
therapies for HCC from both preclinical and clinical perspectives.