Dll4/Notch1 signaling from tip/stalk endothelial cell specification to stroma-dependent lung tumor inhibition: a flavor of Dll4/Notch1 pleiotropy in tumor cell biology.

Non-small cell lung cancer (NSCLC) still represents the leading cause of cancer death. Treating this disease with systemic chemotherapy has reached a plateau in effectiveness and is rather toxic to the patients, while molecularly targeted therapies against Epidermal Growth Factor Receptor can lead to resistance. On the other hand, therapies based on tumor angiogenesis inhibition have been recently proposed. Here we will discuss on the pleiotropy of the Dll4/Notch1 cell-to-cell signaling in NSCLC, as alternative target for future therapeutic approaches.