From bench to bedside: RNA therapies for Liver Cancers

RNA therapeutics represent a transformative approach for the treatment of liver cancers, addressing the limitations of conventional treatments like surgery, chemotherapy, and targeted therapies, which often face resistance, toxicity, and inefficacy in advanced stages. By directly modulating gene expression, RNA-based strategies (including small interfering RNA, microRNA, messenger RNA, and small activating RNA) can target molecular pathways critical to tumor progression. Innovations in technologies for the delivery of therapies to tumors include using biological or synthetic nanocarriers that enhance RNA stability, enable tumor-specific delivery, and allow controlled release in response to the tumor microenvironment. These innovative delivery systems could minimize systemic toxicity and improve therapeutic precision. Promising results of preclinical studies with several different RNA therapies have shown tumor growth inhibition or regression and they highlight the progress being made for their translation for clinical use. However, while RNA therapies offer the potential for targeted action and reduced off-target effects, challenges remain in optimizing delivery, ensuring long-term safety, and managing costs. Advances in design of delivery nanocarriers and use of these therapies in combination regimens with immunotherapy or kinase inhibitors will be necessary to overcome tumor heterogeneity and resistance. In summary, RNA therapeutics, bolstered by nanotechnology and targeted delivery platforms, provide a versatile and promising frontier for personalized treatment of liver cancers, with several promising candidates poised to enter clinical practice.