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REVIEW

Current and Future Landscape of Hepatocellular Carcinoma Treatment

Shadi Zerehpoosh1, Yasuhito Tanaka2, Said A. Al-Busafi3,4, Gulnara Aghayeva5, Samir Rouabhia6, Qiuwei Pan7, Mohammed Eslam1,*
1 Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
2 Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-Ku, Kumamoto, Japan
3 Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
4 Medical Research Center, Sultan Qaboos University, Muscat, Oman
5 Liver Diseases Department, Baku Health Center, Baku, Azerbaijan
6 Department of Internal Medicine, University Hospital Center Touhami Benflis, Batna, Algeria
7 Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
* Corresponding Author: Mohammed Eslam. Email: email
(This article belongs to the Special Issue: Advancements in Hepatocellular Carcinoma Treatment)

Oncology Research https://doi.org/10.32604/or.2026.076937

Received 29 November 2025; Accepted 17 March 2026; Published online 30 March 2026

Abstract

Hepatocellular carcinoma (HCC) represents a critical global health challenge, standing as a leading cause of cancer mortality with a significant and projected increasing incidence worldwide. A primary hurdle in HCC management is late diagnosis, often attributable to the absence of early symptoms. Despite considerable advancements in therapeutic strategies over the past decade, including immune checkpoint inhibitors and targeted therapies, mortality rates remain high, underscoring the urgent need for more effective novel approaches. The inherent molecular complexity and heterogeneity of HCC, where only a minority of tumors possess readily targetable drivers, contribute to treatment resistance and recurrence, even after curative interventions. Addressing these challenges, combination therapies, integrating immunotherapy with targeted agents, are emerging as a promising strategy to enhance efficacy and overcome resistance. This review comprehensively explores the current landscape of HCC treatment and the advancements in systemic therapies, including molecularly targeted agents and immunotherapies, and highlights ongoing challenges and future directions in this rapidly evolving field.

Keywords

Hepatocellular carcinoma (HCC); immunotherapy; targeted therapy; combination therapy; systemic therapy

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