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. 2022 Sep 7;82(22):4126–4138. doi: 10.1158/0008-5472.CAN-22-0948

Figure 6.

Figure 6. Treatment-induced changes in phosphorylation of EGFR, AKT, ERK, and p38 at 6 and 24 hours in lung PDX models treated with erlotinib, afatinib, cetuximab, and afatinib+cetuximab. Studies were conducted in triplicate for each time point, independently in different animals. AKT, ERK1, and p38 phosphorylation state were examined to evaluate changes in downstream signal transduction, with the understanding that the timing of effects will be subject to variation across models. A, In model TM00199, a single treatment of erlotinib and afatinib induced downregulation of EGFR phosphorylation within six hours, rebounding to control levels after 24 hours. Treatment with cetuximab demonstrated moderate downregulation by six hours in two of three models and substantial downregulation at 24 hours in three of three models, accompanied by diminished total protein expression. The combination of afatinib plus cetuximab resulted in ablated phosphorylation at 6 hours in two of three models, maintained at the 24 timepoints, associated with reduced protein expression. B, In model TM00219,none of the EGFR-targeted agents could entirely suppress EGFR phosphorylation at 6 or 24 hours.

Treatment-induced changes in phosphorylation of EGFR, AKT, ERK, and p38 at 6 and 24 hours in lung PDX models treated with erlotinib, afatinib, cetuximab, and afatinib+cetuximab. Studies were conducted in triplicate for each time point, independently in different animals. AKT, ERK1, and p38 phosphorylation state were examined to evaluate changes in downstream signal transduction, with the understanding that the timing of effects will be subject to variation across models. A, In model TM00199, a single treatment of erlotinib and afatinib induced downregulation of EGFR phosphorylation within six hours, rebounding to control levels after 24 hours. Treatment with cetuximab demonstrated moderate downregulation by six hours in two of three models and substantial downregulation at 24 hours in three of three models, accompanied by diminished total protein expression. The combination of afatinib plus cetuximab resulted in ablated phosphorylation at 6 hours in two of three models, maintained at the 24 time points, associated with reduced protein expression. B, In model TM00219, none of the EGFR-targeted agents could entirely suppress EGFR phosphorylation at 6 or 24 hours.