Personalized therapy for lung cancer: striking a moving target

Molecular targeted therapy heralded a new era for the treatment of patients with oncogene-driven advanced-stage non–small-cell lung cancer (NSCLC). Molecular testing at the time of diagnosis guides therapy selection, and targeted therapies in patients with activating mutations in EGFR, BRAF, and rearrangements in anaplastic lymphoma kinase (ALK) and ROS1 have become part of routine care. These therapies have extended the median survival from a mere few months to greater than 3 years for patients with stage 4 disease. However, despite the initial success, these treatments are eventually met with molecular resistance. Selective pressure leads to cellular adaption to maintain cancer growth, making resistance complex and the treatment challenging. This review focuses on recent advances in targeted therapy, mechanisms of resistance, and therapeutic strategies to overcome resistance in patients with lung cancer.