Epidermal growth factor receptor tyrosine kinase inhibitors for non-small cell lung cancer

Figure 2 Major mechanisms of epidermal growth factor receptor resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in lung cancer cell. Secondary epidermal growth factor receptor (EGFR) T790M mutation prevents binding of first-generation EGFR-tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib to EGFR, resulting in cancer cell survival (A). Afatinib inhibits the ATP-binding site of the tyrosine kinase associated with EGFR T790M, leading to apoptosis of cancer cell. MET amplification has been shown to confer resistance to EGFR-TKIs by activating phosphorylation of ErbB3 with activating of the PI3K/AKT pathway, resulting in cancer cell survival (B).