Key Points

• Lung cancer is the leading cause of cancer-related death, with a worldwide reported incidence of 1.83 million and mortality of 1.59 million.
• The epidemiologic evidence of the association between tobacco smoke and lung cancer has become irrefutable, and investigations into the underlying biology have provided further support.
• Lung cancer has one of the highest numbers of somatic mutations, resulting in genomic instability, which enables cancer development and progression.
• The biology of lung cancer results in dysregulation of all of the hallmarks of cancer, including sustaining proliferative signaling, evading growth suppressors, resisting cell death, inducing angiogenesis, enabling replicative immortality, and activating invasion and metastasis.
• The identification of oncogenic drivers through genomic analysis during the past decade has resulted in a paradigm shift in the treatment of non-small cell lung cancer (NSCLC), with targeted therapies and immunotherapy now in the forefront.
• Despite advances in the understanding of the biology and in the treatment of lung cancer, overall survival (OS) remains low, which in part reflects the resistance that emerges during treatment.