title: Notch Antagonists: Potential Modulators of Cancer and Inflammatory Diseases.
abstract: Notch is a key player in various developmental processes during the embryonic stage as well as in regulating tissue homeostasis, cell differentiation, and stem cell maintenance in adult life. Activation of Notch signaling occurs following Notch receptor-ligand interaction and subsequent enzymatic proteolysis by the gamma-secretase complex, resulting in the cytoplasmic release of a Notch intracellular domain, which translocates to the nucleus to initiate the downstream transcriptional machinery. Notch activation and its aberrant signaling have been broadly linked to the pathogenesis of cancer and some chronic inflammatory diseases resulting in pathologic fibrotic processes. This review focuses on the molecular basis of Notch-induced signaling and its interaction with other pathways to identify therapeutic targets. We also highlight current efforts to pharmacologically intervene in Notch signaling and discuss promising ongoing experimental and clinical studies.
authors.affiliation: Transplantation Center and Transplantation Immunopathology Laboratory, Department of Medicine and ‡University Institute of Pathology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL) , CH-1011 Lausanne, Switzerland.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Transplantation Center and Transplantation Immunopathology Laboratory, Department of Medicine and ‡University Institute of Pathology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL) , CH-1011 Lausanne, Switzerland.
authors.forename: Lucienne
authors.initials: L
authors.lastname: Juillerat-Jeanneret
authors.affiliation: Transplantation Center and Transplantation Immunopathology Laboratory, Department of Medicine and ‡University Institute of Pathology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL) , CH-1011 Lausanne, Switzerland.
authors.forename: Dela
authors.initials: D
authors.lastname: Golshayan
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D002986:Clinical Trials as Topic; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016147:Genes, Tumor Suppressor; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D051880:Receptors, Notch / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D008024:Ligands; D051880:Receptors, Notch; D053829:Amyloid Precursor Protein Secretases