Molecular Pathways: Translational and Therapeutic Implications of the Notch Signaling Pathway in Cancer

摘要: Over 100 years have passed since the first observation of notched wing phenotype in Drosophila melanogaster, and significant progress has been made to characterize role Notch receptor, its ligands, downstream targets, cross-talk with other signaling pathways. The canonical pathway four receptors (Notch1-4) five ligands (DLL1, 3-4, Jagged 1-2) is an evolutionarily conserved cell that plays critical roles cell-fate determination, differentiation, development, tissue patterning, proliferation, death. In cancer, these a impact on tumor behavior response therapy. Because remains context dependent, alterations within this may lead suppressive or oncogenic phenotypes. Although no FDA-approved therapies currently exist for pathway, multiple therapeutics (e.g., demcizumab, tarextumab, GSI MK-0752, R04929097, PF63084014) developed target different aspects both hematologic solid malignancies. Understanding context-specific effects will be important individualized targeting pathway.