Lung cancer is the leading cause of cancer mortality worldwide. Comprehensive genomic profiling of lung cancers revealed their genetic heterogeneity and complexity and identified numerous targetable oncogenic driver alterations. These molecular profiling efforts have made it possible to exploit the potential of molecularly targeted therapies. Selection of patients for targeted therapies is becoming biomarker-driven, where the oncogenic drivers in patient tumors are first identified, and subsequently patients bearing drug-sensitizing genetic aberrations are matched to the appropriate targeted therapy. Success of this design of clinical trials and practice was first demonstrated in EGFR inhibitor trials in lung cancer and has since been incorporated into subsequent targeted therapy trials including ALK-, ROS1-, and BRAF V600E-targeted therapies. In this review we discuss the current landscape of clinically approved and other promising molecularly targeted approaches for the treatment of lung cancers, the challenges with these approaches, and the strategies that could be deployed to overcome these challenges.
© 2017 American Society for Clinical Pharmacology and Therapeutics.