Lung cancer is the leading cause of cancer related death in the world. Current therapies are only partially successful and relapse is frequent in a large number of patients. Hence, new therapeutic strategies are needed to improve the quality of life and survival of NSCLC patients.

The Notch pathway is a key pathway involved in cell fate determination during development in many tissues and also in tissue homeostasis during adulthood [1]. Deregulation of the Notch pathway has been implicated in many human diseases including cancer. Interestingly, the Notch pathway can be oncogenic or tumor suppressive depending on the cellular type. For example, gain-offunction mutations that hyperactivate the pathway are a common cause of acute T-cell lymphoblastic leukemia (T-ALL), while head and neck squamous cancers present loss-of-function mutations of the Notch pathway [1]. In the case of NSCLC, gain-of-function mutations have been found in a small percentage of patients [2, 3] and high Notch pathway activity correlates with poor prognosis [3, 4].