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Updated: May 13, 2025
A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
The evolving landscape of biomarkers for systemic therapy in advanced hepatocellular carcinoma
Xinyu Guo1,2, Zhongwei Zhao1,2, Lingyi Zhu3
1Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, School of Medicine, Lishui Hospital, Zhejiaing University, Lishui, 323000, China.
Abstract:
Hepatocellular carcinoma (HCC) remains one of the most prevalent and deadliest cancers. With the approval of multiple first- and second-line agents, especially the combination therapies based on immune checkpoint inhibitor (ICI) regimens, the landscape of systemic therapy for advanced HCC (aHCC) is more diverse than ever before. The efficacy of current systemic therapies shows great heterogeneity in patients with aHCC, thereby identifying biomarkers for response prediction and patient stratification has become an urgent need. The main biomarkers for systemic therapy in hepatocellular carcinoma are derived from peripheral blood, tissues, and imaging. Currently, the understanding of the clinical response to systemic therapy indicates unequivocally that a single biomarker cannot be used to identify patients who are likely to benefit from these treatments. In this review, we provide an integrated landscape of the recent development in molecular targeted therapies and ICIs-based therapies, especially focusing on the role of clinically applicable predictive biomarkers. Additionally, we further highlight the latest advancements in biomarker-driven therapies, including targeted treatments, adoptive cell therapies, and bispecific antibodies.
Insights
Identifying biomarkers is crucial for predicting treatment response in advanced hepatocellular carcinoma (HCC). This review explores molecular targeted therapies and immune checkpoint inhibitor (ICI) regimens, highlighting the need for multi-biomarker approaches.
Area of Science:
- Hepatology
- Oncology
- Cancer Biomarkers
Background:
- Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally.
- Systemic therapies for advanced HCC (aHCC), including immune checkpoint inhibitors (ICIs), offer diverse treatment options.
- Significant heterogeneity exists in patient response to current aHCC therapies.
Purpose of the Study:
- To review recent advancements in molecular targeted therapies and ICI-based treatments for aHCC.
- To focus on the role of clinically applicable predictive biomarkers in guiding therapy selection.
- To highlight emerging biomarker-driven therapeutic strategies.
Main Methods:
- Literature review of recent developments in targeted therapies and ICIs for HCC.
- Analysis of current and emerging predictive biomarkers from blood, tissue, and imaging.
- Exploration of novel therapeutic modalities like adoptive cell therapies and bispecific antibodies.
Main Results:
- The efficacy of systemic therapies for aHCC varies greatly among patients.
- No single biomarker is sufficient for predicting response to current treatments.
- Multi-biomarker strategies are essential for patient stratification and personalized therapy.
Conclusions:
- Predictive biomarkers are urgently needed to optimize systemic therapy for advanced HCC.
- Integrated biomarker approaches are key to improving treatment outcomes.
- Future directions include biomarker-driven targeted treatments, adoptive cell therapies, and bispecific antibodies.
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