Figure 6

Possible EGFR signaling pathways affected by cetuximab. ➀EGF activates EGFR/MAPK signaling. ➁ Phosphorylation of downstream signaling is induced more quickly by TGF-α and IGF than EGF. ➂Potential negative-feedback from downstream signals. ➃Cetuximab reduces the phosphorylation level induced by the three growth factors. ➄Cetuximab binding to the receptor induces the receptor dimerization resulting in protein phosphorylation of downstream proteins. However, inhibition of the receptor internalization leads to the suppression of protein phosphorylation in downstream proteins (as a consequence, in the presence of cetuximab, the level of protein phosphorylation does exist but at a very low level).