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Hepatocellular carcinoma (HCC) is a very aggressive disease and represents the most frequent form of liver cancer. Although treatment of HCC has greatly improved over the last decade, most patients with HCC diagnosed at advanced stages are ineligible for curative ablative therapies such as liver resection or liver transplantation.1 Several multikinase inhibitors, including sorafenib, regorafenib, lenvatinib and cabozantinib, are approved by the Food and Drug Administration for the treatment of patients with advanced HCC, providing limited survival benefits.1 In the last 2 years, the programmed cell death receptor 1 (PD-1) immune checkpoint inhibitors (ICIs) nivolumab and pembrolizumab have also been approved for the treatment of patients with advanced HCC. While immunotherapies have aroused tremendous enthusiasm among clinicians and scientists,2 only a small percentage of patients respond with clinical benefit. One strategy to improve clinical outcomes would be to select those patients who are most likely to respond to ICIs by defining accurate and validated biomarkers of response. A second approach, which is somehow bolder, is to combine two drugs that synergise at killing the tumour cells. In fact, combination immunotherapies have proven effective in melanoma,3 where the first immunotherapy sensitises the tumour cells to the second one.
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