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. 2015 Oct 19;6(38):40850–40865. doi: 10.18632/oncotarget.5813

Figure 9. Mechanism of cetuximab reversing MDR.

Figure 9

When absence of cetuximab, EGF or TGFα can bind to the EGFR resulting in phosphorylation of EGFR and activation of EGFR signaling pathways. As a lipid flippase, ABCB1 has complex interplay with cell membrane and play major function by located in the lipid rafts A. However, at the presence of cetuximab, it can block the binding of endogenous EGFR ligands leading to the inhibition of receptor function and induce EGFR internalization. Cetuximab decrease cell membrane fluidity by regulating EGFR trafficking/turnover and facilitating a switch from lipid rafts to clathrin-mediated endocytosis. The change of the membrane fluidity inhibits the function of ABCB1. As a result, alteration of cell membrane fluidity inhibited the ABCB1 function of extrusion drug out of MDR cells B. Thus, cetuximab can enhance the efficacy of chemotherapeutic agent in ABCB1 mediated-MDR cells.