مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Recent Advances in Systemic Therapy for Hepatocellular Carcinoma
Recent Advances in Systemic Therapy for Hepatocellular Carcinoma
Faezeh Arghidash,1,*
1. Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Introduction: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with an increasing incidence, especially in Asia and Africa (1, 2). Due to delayed diagnosis and limited early screening, most patients are diagnosed at advanced stages when surgical options are no longer feasible (3, 4). Traditional treatments such as surgery or ablation are often insufficient, prompting the development of systemic therapies, including targeted drugs and immune checkpoint inhibitors (ICIs), which have shown promising results in prolonging survival and improving quality of life (5, 6). Recent studies demonstrate that combination strategies, integrating molecular targeted therapies with ICIs, can enhance treatment efficacy through synergistic mechanisms, with some regimens achieving median overall survival (OS) exceeding 20 months (7, 8). The need for more research and individualized treatment strategies is highlighted by the difficulties that still exist, such as drug resistance, tumor heterogeneity, and managing toxicities.
Methods: The present study was conducted based on the review of published studies in PubMed, Scopus, and Web of Science, and all studies were reviewed until 2025.
Results: Recent clinical studies and reviews indicate notable advancements in the systemic treatment of HCC. Targeted therapies such as Sorafenib and Lenvatinib have demonstrated the ability to prolong median survival, with Lenvatinib achieving a median OS of 13.6 months, slightly surpassing Sorafenib’s 12.3 months. However, issues like drug resistance and adverse effects continue to pose challenges. In addition, combination treatments that include anti-angiogenic agents and ICIs have shown promising outcomes. The IMbrave150 study, for instance, found that the combination of Atezolizumab and Bevacizumab significantly increased median OS to 19.2 months, compared to 13.4 months with Sorafenib, and has become a new standard as a first-line therapy for advanced HCC. Furthermore, the LEAP-002 trial reported that pairing Lenvatinib with Pembrolizumab extended median survival to 21.2 months, indicating a meaningful survival advantage over single-agent treatments. Moreover, dual immunotherapy using Nivolumab combined with Ipilimumab achieved a median OS of 22.2 months and an objective response rate of 34%, demonstrating the potential of combined immune checkpoint blockade to improve patient outcomes. These findings emphasize that multi-component treatment strategies can significantly enhance prognosis, though ongoing issues like resistance and patient variability highlight the necessity for further personalized therapeutic approaches.
Conclusion: In summary, substantial progress has been achieved in the systemic management of hepatocellular carcinoma, primarily through the development of targeted therapies and combination treatment strategies. While agents like Sorafenib and Lenvatinib offer some survival extension, recent innovations-such as combining ICIs with anti-angiogenic drugs-have markedly enhanced treatment outcomes and prolonged patient survival. This evolution reflects a transition from monotherapies to more comprehensive, multimodal approaches tailored to individual patient profiles. Nonetheless, issues such as drug resistance and adverse reactions continue to pose significant challenges, highlighting the need for continued research to refine therapeutic efficacy, improve safety profiles, and facilitate personalized treatment plans.