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Updated: Dec 31, 2025
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Hepatocyte Growth Factor Receptor overexpression predicts reduced survival but its targeting is not effective in
Martin Khan1, Sami S Khaznadar2, Johannes Routila3,4
1Charité, Berlin, Augustenburger Platz 1, Berlin, Germany.
Background:
MET has emerged as target in head and neck squamous cell carcinoma (HNSCC). However, clinical data on MET inhibition in HNSCC are limited.
Methods:
HNSCC biopsies and cell lines were tested for MET activity. The response of cell lines to BAY-853474 was tested in proliferation assays. The prognostic value of MET expression was also analyzed.
Results:
HNSCC cell lines do not respond to MET inhibition. MET-dependent gastric cancer cell lines have much higher levels of MET expression and phosphorylation than HNSCC cell lines. Clinical samples of HNSCC contain much less MET than responsive models.
Conclusions:
No clinical response to MET inhibitors in monotherapy may be expected in unselected cases of HNSCC. Only selected patients with MET amplifications should be treated with MET inhibitors. Patients with increased MET immunoreactivity have shorter overall survival. MET might be useful as marker for the detection of patients with more aggressive types of HNSCC.
Insights
Head and neck squamous cell carcinoma (HNSCC) cell lines show limited response to MET inhibition. MET expression levels in HNSCC are lower than in responsive cancers, suggesting targeted therapy should be selective.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The MET pathway is a potential therapeutic target in head and neck squamous cell carcinoma (HNSCC).
- Clinical evidence regarding the efficacy of MET inhibition in HNSCC is currently scarce.
Purpose of the Study:
- To investigate MET activity in HNSCC.
- To evaluate the response of HNSCC cell lines to MET inhibition.
- To determine the prognostic significance of MET expression in HNSCC.
Main Methods:
- Analysis of MET activity in HNSCC biopsies and cell lines.
- Assessment of HNSCC cell line proliferation in response to the MET inhibitor BAY-853474.
- Evaluation of the correlation between MET expression and patient survival.
Main Results:
- HNSCC cell lines demonstrated a lack of response to MET inhibition.
- MET-dependent gastric cancer cell lines exhibited significantly higher MET expression and phosphorylation compared to HNSCC cell lines.
- Clinical HNSCC samples showed substantially lower MET levels than responsive cancer models.
Conclusions:
- Monotherapy with MET inhibitors is unlikely to be effective in unselected HNSCC patients.
- MET inhibitors should be considered only for HNSCC patients with confirmed MET amplifications.
- Elevated MET immunoreactivity in HNSCC patients correlates with shorter overall survival, indicating MET's potential as a biomarker for aggressive disease.
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