RNA-based therapies in hepatocellular carcinoma: state of the art and clinical perspectives

Liver cancer is a heterogeneous disease and is one of the leading causes of cancer deaths worldwide. Hepatocellular carcinoma, comprising approximately 90% of cases, presents a formidable challenge with a less than 20% 5-year survival rate despite recent treatment advancements. The impediments of drug resistance and off-target effects underscore the critical need for innovative and efficacious therapies. Harnessing the growing understanding of RNA function offers a promising avenue to address previously "undruggable" proteins, transcripts, and genes. Various RNAs demonstrate the potential to selectively act on these targets, expanding the scope of therapeutic interventions. With diverse regulatory roles in cancer pathways, RNAs emerge as valuable targets and tools for anticancer therapy development. This article provides an in-depth exploration of current RNA-based therapies, elucidates their mechanisms of action, and discusses their combinations with chemo-/immunotherapies in clinical trials for hepatocellular carcinoma.