Potential Predictive Biomarkers of Systemic Drug Therapy for Hepatocellular Carcinoma: Anticipated Usefulness in Clinical Practice

Abstract

In the systemic drug treatment of hepatocellular carcinoma, only the tyrosine kinase inhibitor (TKI) sorafenib was available for a period. This was followed by the development of regorafenib as a second-line treatment after sorafenib, and then lenvatinib, a new TKI, proved non-inferiority to sorafenib and became available as a first-line treatment. Subsequently, cabozantinib, another TKI, was introduced as a second-line treatment, along with ramucirumab, the only drug proven to be predictive of therapeutic efficacy when AFP levels are >400 ng/mL. It is an anti-VEGF receptor antibody. More recently, immune checkpoint inhibitors have become the mainstay of systemic therapy and can now be used as a first-line standard treatment for HCC. However, the objective response rate for these drugs is currently only 30% to 40%, and there is a high incidence of side effects. Additionally, there are no practical biomarkers to predict their therapeutic effects. Therefore, this review provides an overview of extensive research conducted on potential HCC biomarkers from blood, tissue, or imaging information that can be used in practice to predict the therapeutic efficacy of systemic therapy before its initiation.