Background: Hepatocellular carcinoma (HCC) is among the world’s most common cancers. For
over ten years, the only medical treatment for it has been the multikinase inhibitor Sorafenib. Currently, however,
other first or second-line therapeutic options have also shown efficacy against HCC, such as multikinase inhibitors
(Regorafenib, Lenvatinib, and Cabozantinib), a monoclonal antibody against the vascular endothelial
growth factor receptor 2 (Ramucirumab), and immune-checkpoint inhibitors (Nivolumab, Pembrolizumab, Ipilimumab).
Aim: The aim of this paper is to review the metabolic pathways of drugs that have been tested for the treatment
of HCC and the potential influence of liver failure over those pathways.
Methods: The Food and Drug Administration (FDA)’s and European Medicines Agency (EMA)’s datasheets,
results from clinical trials and observational studies have been reviewed.
Results: This review summarizes the current knowledge regarding targets, metabolic pathways, drug interactions,
and adverse events of medical treatments for HCC in cirrhotic patients.
Conclusion: The new scenario of systemic HCC therapy includes more active drugs with different metabolic
pathways and different liver adverse events. Clinical and pharmacological studies providing more data on the
safety of these molecules are urgently needed.