Advancing Hepatocellular Carcinoma Therapy with Next-Generation Molecular and Immunotherapeutics

Hepatocellular carcinoma (HCC), the most prevalent form of primary liver cancer, remains a major global health concern due to its high incidence and mortality rates. Driven by factors such as chronic hepatitis B and C infections, alcohol-related liver disease, and metabolic-associated fatty liver disease (MAFLD), HCC is often diagnosed at advanced stages, limiting therapeutic options and prognosis. Recent advances in understanding the molecular mechanisms and tumor microenvironment of HCC, particularly disruptions in key pathways like Ras-Raf-MEK, PI3K-Akt/mTOR, and Wnt/β-catenin, have catalyzed the development of novel treatment strategies. This review synthesizes findings from over 80 recent peer-reviewed studies to explore the evolution of HCC therapy, including targeted therapies, immune checkpoint inhibitors, combination regimens, surgical techniques, and locoregional treatments. Special emphasis is placed on the role of tumor immunology, emerging biomarkers, and the impact of precision medicine in tailoring treatment strategies. These innovations collectively offer promising avenues for improving survival and quality of life in patients with HCC.