Molecular perspectives for the treatment of hepatocellular carcinoma

Major advances have been performed in the understanding of genomic dysregulation of hepatocellular carcinoma. A median of 40 to 60 somatic mutations in coding sequence per tumor was identified including 2 to 6 mutations per tumor in genes driving liver carcinogenesis. The main genetic alterations target the key signaling pathways of liver carcinogenesis : telomere maintenance, cell cycle gene, Wnt/beta-catenin pathway, epigenetic modifier gene, oxidative stress pathway, AKT/mTOR and Ras/Raf MAP kinase pathways. A genotype/phenotype classification between these genetic drivers the tumor and patient’s features have been also described and was correlated with transcriptomic profiling. These data will be helpful to identify subgroups of HCC that will respond or resist to systemic treatments already used in clinical practice such as tyrosine kinase inhibitors, anti-VEGFR antibody or checkpoint inhibitors and will be useful to identify new therapeutic targets tested in future clinical trials.

Keywords: molecular classification, hepatocellular carcinoma, targeted therapy, immunotherapy, predicitive biomarker, tyrosine kinase inhibitor.