Overcoming Resistance to Targeted Therapy for Lung Cancer

The discovery that certain activating mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain may determine responses to EGFR tyrosine kinase inhibitors in patients with advanced non–small-cell lung cancer (NSCLC) allowed more precise selection of patients who were likely to have a response.1,2 These mutations are seen in approximately 10 to 15% of metastatic NSCLC tumors, mostly in patients with adenocarcinoma who have never smoked. As compared with cytotoxic chemotherapy, EGFR tyrosine kinase inhibitors significantly improve the overall response rate and progression-free survival in previously untreated patients with EGFR-mutated NSCLC.35 However, despite their . . .