Antitumor effect of vandetanib through EGFR inhibition in head and neck squamous cell carcinoma

作者：Klein Jonah D; Christopoulos Apostolos; Ahn Sun M; Gooding William E; Grandis Jennifer R; Kim Seungwon^*

来源：Head and Neck-Journal for the Sciences and Specialties of the Head and Neck, 2012, 34(9): 1269-1276.

DOI：10.1002/hed.21917

• vandetanib
• HNSCC
• EGFR
• angiogenesis
• molecular targeted therapy

Background The epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) have been implicated as therapeutic targets for head and neck squamous cell carcinoma (HNSCC). Vandetanib is a small-molecule tyrosine kinase inhibitor (TKI) with dual specificity for EGFR and VEGFR. Here we characterize the phenotypic and biochemical effects of vandetanib on various HNSCC cell lines. Methods In vitro models were used for studying tumor cell viability, invasion, and signaling as well as in vivo xenograft models. Results Treatment with vandetanib reduced viability, invasion, and tumor growth of HNSCC cell lines. Phosphorylation levels of mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) were reduced in vandetanib-treated HNSCC cells. Additionally, vandetanib abrogates EGF-induced STAT3 activity and STAT3 target gene expression. Conclusions We demonstrated that vandetanib inhibits the growth of head and neck cancer cell lines. The antitumor effects of vandetanib appear to be exerted via the EGFR inhibitory effect of the compound.

• 出版日期2012-9