Project Summary Abstract Lung cancer remains the leading cause of cancer related mortality in the US and globally— responsible for ~1.8 million deaths annually. As collaborative investigators of the Cancer Intervention and Surveillance Modeling Network (CISNET) Lung Working Group (LWG), we have contributed to the development of US national strategies for reducing the lung cancer burden by quantifying the impact of tobacco control on smoking, lung cancer, and overall mortality, and by evaluating the population benefits and harms of lung cancer screening in the US. Due to ongoing reductions in smoking in the US, lung cancer mortality is projected to continue declining. However, lung cancer is still expected to result in over 4 million deaths over the next 50 years. Thus, in addition to tobacco control efforts, a focus on early detection and treatment interventions will be critical to further reduce the lung cancer burden in the US. Moreover, as new tobacco products, such as e-cigarettes (e-cigs), become more popular, there are concerns that the gains achieved in the fight against smoking could reverse. We propose to continue our work and extend our models to assess the impact of 1) future tobacco control interventions in the ever-changing tobacco market landscape, 2) improvements in lung cancer screening and other emerging early detection strategies, 3) innovations in lung cancer treatment, and importantly, 4) their synergistic interactions on lung cancer rates and overall mortality in the US and globally.