Over a short period of time, translational research has described a new clinically relevant molecular subset of non-small-cell lung cancer (NSCLC) that is defined by EGFR mutations or EML4-ALK fusions. Today, patients with metastatic disease can achieve survival rates at least double that of patients with wild-type tumors. Through the rational dissection of the mechanisms of drug sensitivity and resistance, promising strategies have been defined to further improve the outcomes of patients with NCSLC. This review adds to a growing body of knowledge into mechanisms of resistance that can be interrogated in NSCLC patients with EGFR mutations or EML4-ALK fusions, as well as strategies to overcome resistance to TKIs.
Keywords: EGFR; EML4–ALK; TKI resistance; lung cancer; tyrosine kinase inhibitors.