Current perspectives and future strategies for the systemic treatment of hepatocellular carcinoma: a narrative review
- Author:
Hong Jae CHON
1
Author Information
- Publication Type:Focused Issue of This Month
- From:Journal of the Korean Medical Association 2025;68(12):809-817
- CountryRepublic of Korea
- Language:Korean
- Abstract: Hepatocellular carcinoma (HCC) is a highly aggressive malignancy that ranks among the top three causes of cancer-related mortality worldwide. Although the development of systemic therapies for HCC historically lagged behind that of other solid tumors, the recent emergence of immune checkpoint inhibitors (ICIs) and targeted agents has substantially reshaped the therapeutic landscape.Current Concepts: ICI-based combination therapies, such as atezolizumab plus bevacizumab (IMbrave150), durvalumab plus tremelimumab (HIMALAYA), and nivolumab plus ipilimumab (CheckMate-9DW), have become new standards of care for first-line treatment of advanced HCC. These regimens have demonstrated superior overall survival compared with tyrosine kinase inhibitors (TKIs); however, objective response rates remain limited to approximately 20% to 30%. As treatment advances beyond the first line, TKIs including sorafenib, lenvatinib, regorafenib, and cabozantinib continue to serve as key second- or third-line options. In parallel, emerging strategies—such as salvage immunotherapy, locoregional treatment for oligoprogression, and multidisciplinary care—are receiving increasing attention.Discussion and Conclusion: Despite recent therapeutic advances, the management of advanced HCC remains challenging because of underlying liver dysfunction, marked tumor heterogeneity, and the absence of robust predictive biomarkers. Personalized treatment strategies that incorporate liver function, performance status, and comorbidities are therefore essential. Future efforts should prioritize the identification of predictive biomarkers and the development of more effective combination approaches. In addition, integrating systemic therapy with locoregional modalities and expanding access to clinical trials will be critical for improving long-term survival outcomes in this patient population.
