PUBLICATION
Targeting of c-MET and AXL by cabozantinib is a potential therapeutic strategy for patients with head and neck cell carcinoma
- Authors
- Hagege, A., Saada-Bouzid, E., Ambrosetti, D., Rastoin, O., Boyer, J., He, X., Rousset, J., Montemagno, C., Doyen, J., Pedeutour, F., Parola, J., Bourget, I., Luciano, F., Bozec, A., Cao, Y., Pagès, G., Dufies, M.
- ID
- ZDB-PUB-220922-16
- Date
- 2022
- Source
- Cell reports. Medicine 3: 100659 (Journal)
- Registered Authors
- Boyer, Julien
- Keywords
- AXL, HNSCC, VEGFR inhibitor, anti-angiogenic, c-MET, cabozantinib, cisplatin, head and neck squamous cell carcinoma, radiotherapy, resistance, therapy repositioning
- MeSH Terms
-
- Anilides
- Animals
- Carcinoma*
- Cell Line, Tumor
- Cisplatin/pharmacology
- Head and Neck Neoplasms*/drug therapy
- Humans
- Mice
- Neoplasm Recurrence, Local
- Proto-Oncogene Proteins/metabolism
- Proto-Oncogene Proteins c-met/metabolism
- Pyridines
- Receptor Protein-Tyrosine Kinases/metabolism
- Squamous Cell Carcinoma of Head and Neck/drug therapy
- Vascular Endothelial Growth Factor A
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 36130479 Full text @ Cell Rep Med
Citation
Hagege, A., Saada-Bouzid, E., Ambrosetti, D., Rastoin, O., Boyer, J., He, X., Rousset, J., Montemagno, C., Doyen, J., Pedeutour, F., Parola, J., Bourget, I., Luciano, F., Bozec, A., Cao, Y., Pagès, G., Dufies, M. (2022) Targeting of c-MET and AXL by cabozantinib is a potential therapeutic strategy for patients with head and neck cell carcinoma. Cell reports. Medicine. 3:100659.
Abstract
Local or metastatic relapse following surgery, radiotherapy, and cisplatin is the leading cause of death in patients with head and neck squamous cell carcinoma (HNSCC). Our study shows overexpression of c-MET and AXL in HNSCC cells and patients resistant to radiotherapy and cisplatin. We demonstrate that cabozantinib, an inhibitor of vascular endothelial growth factor receptor (VEGFR), c-MET, and AXL, decreases migration, invasion, and proliferation and induces mitotic catastrophe and apoptotic cell death of naive and radiotherapy- and cisplatin-resistant HNSCC cells. Cabozantinib inhibits the growth and metastatic spread of experimental HNSCC in zebrafish and the growth of experimental HNSCC in mice by blocking tumor cell proliferation and angiogenesis. The efficacy of cabozantinib is also confirmed on viable sections of surgically removed specimens of human HNSCC and on a patient who relapses after five lines of treatment. These results suggest that cabozantinib is relevant for the treatment of patients with HNSCC after relapse under radiotherapy and cisplatin.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping