Figure 2. EGFR G465R mutation induces cross-resistance to panitumumab and cetuximab in an EGF-dependent Ba/F3 cellular model.

A: EGFR signaling in EGF-dependent Ba/F3 model. Wt and S492R or G465R mutant EGFR-expressing Ba/F3 cells were cultured in the presence or absence of EGF and with addition of cetuximab, panitumumab, rituximab or erlotinib. After 2 hours, cells were harvested and EGFR/pEGFR expression analyzed by western blot analysis. B: Sensitivity of EGFR wt or EGFR G465R mutant-transfected Ba/F3 cells to treatment with EGFR-targeted antibodies. Ba/F3 cells were transformed to IL-3 independence with EGFR wt or mutant constructs and subsequently cultured in the presence or absence of EGF or with EGF in combination with panitumumab, cetuximab or control antibody rituximab. The number of viable cells was determined by trypan blue exclusion every 12 hours beginning 24 hours after seeding and plotted. Data are means from triplicate experiments +/−SEM.