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. 2021 Feb 5;12:1–10. doi: 10.2147/LCTT.S293902

Figure 1.

Figure 1

Schematic illustration of Ras/Raf/MEK/ERK signaling downstream of cell membranes tyrosine kinase receptors including EGFR that negatively regulate apoptosis through modulating degradation of Bim and Mcl-1 (A), mechanism by which osimertinib induces apoptosis in the sensitive EGFR-mutant NSCLC cells though targeting this pathway (A), and rationale for co-targeting mutant EGFR (mEGFR) and MEK/ERK to enhance apoptosis in the resistant EGFR-mutant NSCLC cells (B). The red arrows indicate the changes caused by osimertinib (A) or the combination of osimertinib with a MEK (eg, trametinib) or ERK (eg, GDC0994) inhibitor (B). amp, amplification; mut, mutation.