Liver cancer

mostly hepatocellular carcinoma (HCC)

is the second leading cause of cancer mortality globally. Most patients were diagnosed at an advanced stage

and systemic therapy is the standard of care. All the approved systemic therapies for HCC are molecular targeted therapies with anti-angiogenic effects targeting the vascular endothelial growth factor signaling pathway. Sorafenib and lenvatinib are the first-line treatment

and regorafenib

ramucirumab

and cabozantinib are second-line treatment options. Although anti-PD-1 antibodies

including nivolumab and pembrolizumab

demonstrated promising anti-tumor effects as monotherapy for advanced HCC in phase II clinical trials

both failed in phase III studies. Anti-angiogenic treatment remains the backbone of systemic therapy for HCC. In this review

we summarized the approved anti-angiogenic medicines and discussed the potential strategies to improve the efficacy of anti-angiogenic therapy

including combination therapy with other treatments

and discussed the approaches to overcome the drawbacks of anti-angiogenic therapies.