Dear Colleagues,

Hepatocellular carcinoma (HCC) is the most common primary liver cancer; it frequently occurs in patients with chronic viral hepatitis, alcoholic liver disease, or non-alcoholic steatohepatitis (NASH). It is the sixth most common cancer and the fourth most common cause of cancer-related deaths in the world. Despite the high morbidity rates, only small fraction of HCC patients are eligible for curative treatment such as surgical resection, RFA, and liver transplantation in early stages, while most patients receive palliative treatment such as TACE or systemic target therapy due to late/advanced-stage in diagnosis. Tyrosine kinase inhibitors (TKIs) such as Sorafenib, Levatinib, or Regorafenib have an effect by targeting tumoral angiogenesis and inducing the apoptosis of cancer cells, and are approved in the treatment of advanced HCC by regulatory agencies. Nevertheless, these TKIs yield unsatisfactory clinical benefits, as they are clinically indicative of lower response rates and rapid disease progression. In addition to TKIs for use in systemic HCC treatment, recent progress in immune-modulating therapy and immune-check inhibitors (ICI, anti-PD1/PDL-1), such as Nivolumab and Panbrolizumab, also shed light on the successful treatment of unresectable or metastatic HCC, prolonging patient survival. In particular, amazing results can be seen through the use of the combination of ICI with anti-VEGF therapy, such as Atezolizumab and Bevacizumab, which highlights the possibility of target therapy for advanced HCC, for instance, ICI and target therapy in combination or dual ICIs. These novel therapeutic means have been found to stall hepatocarcinogenesis, modulate the tumor microenvironment, or perturb host innate and adaptive immunity against HCC progression.

This Special Issue in the International Journal of Molecular Sciences entitled “Advancements in hepatocellular carcinoma” will pay particular attention to unexplored molecular mechanisms and signaling events in hepatocarcinogenesis, liver patholphyisiology, the tumor microenvironment, and immune modulation during HCC progression and recurrence, and more importantly, novel strategies to treat or mitigate drug resistance for advanced HCC. We look forward to physicians and researchers interested in the unmet medical needs of advanced hepatocellular carcinoma sharing their exciting translational studies with broad readers and improving our knowledge towards future medical success.

Dr. Ting-Jung Wu
Guest Editor

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• treatment for hepatocellular carcinoma
• hepatocarcinogenesis
• liver pathophysiology
• tumor microenvironment
• immune modulation