The losses of tumor suppressor functions such as p53 or Lkb1 are relatively common genetic alteration events in NSCLC. However, it is unclear how of the losses of these functions impact on the responses of these NSCLC to various therapeutics. In this presentation, we will show preclinical data with genetically engineered mouse models of lung cancer harboring various tumor suppressor losses to demonstrate that they dramatically alter the responses to different classes of targeted therapies.