Emerging uses of biomarkers in lung cancer management: molecular mechanisms of resistance

Management of patients with advanced non-small cell lung cancer (NSCLC) has recently been transformed by molecularly targeted and immunotherapeutic agents. In patients with EGFR/ALK/ROS mutated NSCLC, first line molecular therapy is the standard of care. Moreover, immune checkpoint inhibitors are revolutionary treatment options for advanced NSCLC and are now the standard of care in front-line or later line settings. Both classes of agents have led to improved patient outcomes, however, primary resistance and development of acquired resistance to both targeted and immunotherapeutic agents is commonly observed, limiting the use of these agents in clinical settings. In this review, we will discuss the most recent advances in understanding the mechanisms of primary and acquired resistance, progress in the spectrum of assays detecting causative molecular events and the development of new generations of inhibitors to overcome acquired resistance.