Related Experiment Video
Updated: Sep 21, 2025
Mass Cytometry Analysis of Systemic and Local Immune Responses in Hepatocellular Carcinoma
Published on: April 25, 2025
AXL and MET in Hepatocellular Carcinoma: A Systematic Literature Review
Chih-Hung Hsu1,2, Yi-Hsiang Huang3,4, Shi-Ming Lin5
1Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
Background:
Multikinase inhibitors (MKIs) have been shown to improve survival in patients with hepatocellular carcinoma (HCC) compared with placebo. Distinct from other MKIs, cabozantinib has inhibitory activity for both AXL and MET. This review considers the literature elucidating the role of AXL and MET in HCC progression, treatment resistance, and immunomodulation. A systematic search of the PubMed database was conducted on November 16, 2020, and identified a total of 174 search results. A further 36 potentially relevant articles were identified based on the authors' knowledge. After initial screening by title/abstract, 159 underwent full-text screening and we identified 69 original research articles reporting empirical data from in vitro or in vivo models of HCC evaluating the effects of manipulating AXL or MET signaling on tumorigenic behavior.
Summary:
AXL expression is highly correlated with HCC progression and outcomes and has been reported to be involved in transforming growth factor-β and the regulation of PI3K/AKT, ERK/MAPK, and CCN proteins. MET protein expression is increased in HCC with the highest histological grade and has been reported to be involved in the regulation of PI3K/AKT, PLCγ/DAG/PKC, and MAPK/ERK signaling. Both AXL and MET are key regulators of sorafenib resistance in HCC. In terms of immunomodulation, there are data to indicate that AXL and MET interact with the immune components of the tumor microenvironment and promote tumorigenesis and treatment resistance. In addition, AXL was found to play a potential role in the development of a protumorigenic neutrophil phenotype in HCC. Combined inhibition of MET and programmed cell death protein resulted in additive reduction of HCC cell growth.
Key Messages:
AXL and MET play key roles in HCC progression, treatment resistance, and immunomodulation. Continued development of drugs that target these receptor tyrosine kinases appears likely to represent a useful strategy to improve outcomes for patients with HCC.
Insights
Cabozantinib targets AXL and MET, crucial in hepatocellular carcinoma (HCC) progression and treatment resistance. Inhibiting these pathways may improve HCC patient survival and overcome resistance to therapies like sorafenib.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Hepatocellular carcinoma (HCC) is a significant global health concern.
- Multikinase inhibitors (MKIs) offer improved survival in HCC patients.
- Cabozantinib uniquely inhibits both AXL and MET receptor tyrosine kinases.
Purpose of the Study:
- To review the literature on the roles of AXL and MET in HCC.
- To understand their involvement in HCC progression, treatment resistance, and immunomodulation.
- To evaluate the therapeutic potential of targeting AXL and MET in HCC.
Main Methods:
- Systematic literature search of the PubMed database.
- Inclusion of relevant articles identified through expert knowledge.
- Full-text screening of 159 articles to identify 69 studies reporting empirical data.
Main Results:
- AXL and MET signaling pathways are implicated in HCC progression, poor outcomes, and resistance to therapies like sorafenib.
- Both AXL and MET influence the tumor microenvironment and immune response, promoting tumorigenesis and resistance.
- AXL may contribute to a protumorigenic neutrophil phenotype in HCC.
Conclusions:
- AXL and MET are critical drivers of HCC progression, treatment resistance, and immune evasion.
- Targeting these receptor tyrosine kinases represents a promising therapeutic strategy for improving HCC patient outcomes.
- Combined inhibition strategies, such as MET and PD-1 blockade, show potential for additive anti-tumor effects.
