Skip to main content
. Author manuscript; available in PMC: 2010 Jul 13.
Published in final edited form as: Oncogene. 2008 Feb 25;27(28):3944–3956. doi: 10.1038/onc.2008.19

Figure 8. Model of acquired-resistance to cetuximab and therapeutic strategies to overcome resistance.

Figure 8

Chronic exposure to cetuximab leads to dysregulation of c-Cbl mediated internalization and degradation of the EGFR. This increased steady-state expression of EGFR serves to bind and activate HER2 or HER3 and thereby maintain signaling to MAPK and Akt pathways in the presence of cetuximab. TKIs targeting EGFR and HER2 lead to blockade of HER3 transactivation and subsequent pro-survival signals to Akt. In addition, combinatorial monoclonal antibody therapy using cetuximab and 2C4 leads to inactivation of HER3 and down regulation of its signaling pathways.