In lung cancer, the deregulation of the Notch pathway is mainly correlated with activating missense mutations mostly affecting the ligand-binding domain (EGF repeats 11 and 12) or the ankyrin domains which lead to a ligand-independent activation [50]. NOTCH1 activating mutations have been defined as a common event in human NSCLC [51] and have been correlated to poor prognosis and response to therapy in lung patients without p53 mutations [52]. This evidence concerns the gene NOTCH1 and lung cancer.