Personalized treatment for hepatocellular carcinoma: Current status and future perspectives.

Systemic treatment for hepatocellular carcinoma (HCC) has been advancing rapidly over the last decade. More novel agents, including both targeted agents and immune checkpoint inhibitors, are available for physicians to use sequentially or concurrently for patients with advanced HCC. Despite more options, only a proportion of patients benefit from each regimen. Therefore, clinicians are facing challenges on how to choose the right regimen for the right patient with HCC, which raises the importance of personalized treatment approach. To advance personalized treatment for HCC, one approach relies on the acquisition of biomarker data from clinical trials to evaluate clinical parameters or genotypes in association with outcomes of selected drugs. This approach has led to finding of high baseline alpha-fetoprotein levels in association with benefits of ramucirumab. Cumulative findings from multiple clinical trials and translational studies also suggest that selected etiology and/or genotype of HCC could predict resistance to immune checkpoint inhibitors. The second approach is to decipher the tumor heterogeneity of HCC with an aim to identify clinically relevant patterns to guide clinical decisions. Tumor heterogeneity could exist within a single tumor (intra-tumoral heterogeneity), among different tumors in the same patient (inter-tumoral heterogeneity) or between primary and recurrent tumors (temporal tumor heterogeneity). The analyses of tumor heterogeneity have also been powered by coverage of tumor immune environment and incorporation of circulating tumor nucleic acid technology. Emerging publications have been reported above tumor heterogeneity exist in HCC, which is potentially clinically impactful.