Given their high specificity for their targets (EphB receptors and EphA4 for EFNB2-Fc-His or EphB4 for Fc-TNYL-RAW-GS), the two Fc fusion plasmids are promising agents to combat HNSCC metastasis and circumvent off-target effects of traditional receptor tyrosine kinase inhibitors (Duggineni et al., 2013; Fan et al., 2022; M. Koolpe et al., 2005; Noberini et al., 2011). This evidence concerns the gene EPHB4 and head and neck squamous cell carcinoma.