Fig. 6

Model of cetuximab induced EGFR and IGF-1R interaction. Binding of anti-EGFR antibody cetuximab displaces the EGF ligand which results in disruption of EGFR homodimers. Cetuximab bound monomer of EGFR engages IGF-1R to form a heterodimer. The ligand independent activation of EGFR Y845 is not reduced in the presence of Src inhibitor PP1 (dotted line) but is reduced by IGF-1R inhibitor PPP. The model suggests that intrinsic kinase activity of IGF-1R has the potential to phosphorylate EGFR Y845 due to the heterodimerization of these receptors. This heterodimerization and hence sensitivity to IGF1R mediated phosphorylation is more pronounced in resistant than sensitive cells