Figure 5.

Model for the oncogenic activation of the EGFR signaling pathway and response to therapeutic EGFR-blockade in basal HNSCC. Our results suggest that basal HNSCC cell proliferation and survival are activated by an oncogenic positive feedback loop that is fueled by the expression of EGFR ligands, including epiregulin, and the activation of the EGFR signaling pathway. Pharmacologic blockade of EGFR with monoclonal antibodies or TKIs results in down-regulation of ligand gene expression and diminution of the activity of the EGFR signaling pathway, leading to a decrease in cell viability.