Overcoming therapy resistance in EGFR-mutant lung cancer

Tyrosine kinase inhibitors (TKIs) have dramatically changed the clinical prospects of patients with non-small cell lung cancer harboring epidermal growth factor receptor (EGFR)-activating mutations. Despite prolonged disease control and high tumor response rates, all patients eventually progress on EGFR TKI treatment. Here, we review the mechanisms of acquired EGFR TKI resistance, the methods for monitoring its appearance, as well as current and future efforts to define treatment strategies to overcome resistance. Passaro and colleagues discuss recent advances in treating EGFR-mutant lung cancer, including methods for detecting disease and tracking therapy response, developments in understanding of resistance mechanisms and ongoing clinical trials to circumvent therapeutic resistance to EGFR targeting.