Molecular signatures in hepatocellular carcinoma: A step toward rationally designed cancer therapy

摘要

Molecular characterization of hepatocellular carcinoma (HCC) has greatly improved our understanding of disease pathogenesis. Mutational analysis, RNA and microRNA expression profiling, and epigenetic characterization have revealed common aberrations in oncogenes and tumor suppressors that correlate with disease biology and serve as a guide for the rational design of targeted therapies. These approaches have also led to the discovery of novel targets, including mutations in isocitrate dehydrogenase and chromatin remodeling enzymes. With the advent of immunotherapy, RNA expression profiling of the tumor microenvironment has identified a subset of HCC with high lymphocyte infiltration that may benefit from checkpoint inhibitor therapy. Molecular signatures thus capture the biology of a tumor, providing a supplement to current staging schema, which are based on tumor size and number, for more accurate prognostication of recurrence risk and survival. Molecular signatures may also be used to guide interventional therapy by defining those most suitable for transplantation or locoregional therapy rather than surgical resection. Finally, a multiomics approach involves the aggregation and analysis of multiple signatures for a more comprehensive characterization of pathogenic mechanisms. This broader approach attempts to address issues with signaling pathway cross‐talk and redundancy, which have greatly limited the potential value of targeted therapies to date. Cancer 2018. ? 2018 American Cancer Society .