Clinical implications of the dual blockade of the PD-1/PD-L1 and vascular endothelial growth factor axes in the treatment of hepatocellular carcinoma

Currently, liver cancer is the fourth most common cause of cancer mortality worldwide. The overwhelming majority of liver cancers are hepatocellular carcinomas (HCC), developing on the background of chronic liver diseases, including chronic hepatitis B, chronic hepatitis C, and non-alcoholic steatohepatitis (1). Despite the recent progress in the treatment of HCC, it remains largely refractory, with a high recurrence rate even after therapeutic intervention (2). Numerous agents, including tyrosine-kinase inhibitors (TKIs), antibodies blocking the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) axis, and immune checkpoint inhibitors, are now available for the treatment of advanced stage HCC (3). However, their antitumor responses are still unsatisfactory.