Notch Transduction in Non-Small Cell Lung Cancer

The evolutionarily-conserved Notch signaling pathway plays critical roles in cell communication, function and homeostasis equilibrium. The pathway serves as a cell-to-cell juxtaposed molecular transducer and is crucial in a number of cell processes including cell fate specification, asymmetric cell division and lateral inhibition. Notch also plays critical roles in organismal development, homeostasis, and regeneration, including somitogenesis, left-right asymmetry, neurogenesis, tissue repair, self-renewal and stemness, and its dysregulation has causative roles in a number of congenital and acquired pathologies, including cancer. In the lung, Notch activity is necessary for cell fate specification and expansion, and its aberrant activity is markedly linked to various defects in club cell formation, alveologenesis, and non-small cell lung cancer (NSCLC) development. In this review, we focus on the role this intercellular signaling device plays during lung development and on its functional relevance in proximo-distal cell fate specification, branching morphogenesis, and alveolar cell determination and maturation, then revise its involvement in NSCLC formation, progression and treatment refractoriness, particularly in the context of various mutational statuses associated with NSCLC, and, lastly, conclude by providing a succinct outlook of the therapeutic perspectives of Notch targeting in NSCLC therapy, including an overview on prospective synthetic lethality approaches.