Targeting of c-MET and AXL by cabozantinib is a potential therapeutic strategy for patients with head and neck cell carcinoma.
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
AXL
HNSCC
VEGFR inhibitor
anti-angiogenic
c-MET
cabozantinib
cisplatin
head and neck squamous cell carcinoma
radiotherapy
resistance
therapy repositioning
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
20 09 2022
20 09 2022
Historique:
received:
30
06
2021
revised:
14
01
2022
accepted:
20
05
2022
entrez:
21
9
2022
pubmed:
22
9
2022
medline:
24
9
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36130479
pii: S2666-3791(22)00191-4
doi: 10.1016/j.xcrm.2022.100659
pmc: PMC9512663
pii:
doi:
Substances chimiques
Anilides
0
Proto-Oncogene Proteins
0
Pyridines
0
Vascular Endothelial Growth Factor A
0
cabozantinib
1C39JW444G
Proto-Oncogene Proteins c-met
EC 2.7.10.1
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100659Informations de copyright
Copyright © 2022 CNRS. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests Part of this work was financed by obtaining IPSEN funding. The authors have declared that no conflict of interest exists.
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