title: Targeting Notch as a Therapeutic Approach for Human Malignancies.
abstract: Notch is a multifaceted protein that plays a fundamental role in fetal development and tissue homeostasis by directing many cellular functions, including cell growth and differentiation, cell fate determination and regulation of stem cells maintenance. The Notch family consists of four receptors (Notch 1-4) and five ligands (Jagged1-2 and Delta-like 1-3-4) widely expressed in human tissues. Given the crucial contribution of Notch signaling in many physiological processes, it is not surprising that a variety of human malignancies is characterized by a dysregulation of one or more components of this pathway.
  
  
  
  In this review, we are going to provide a broad overview on the role of Notch pathway in solid and hematological malignancies and a survey on possible Notch-directed therapeutic strategies.
  
  
  
  We present the most recent findings indicating that Notch signaling dysregulation in human cancers may be due to genetic and epigenetic alterations or to the interactions with other oncogenic pathways. Furthermore, Notch activity may have an oncogenic or a tumor suppressor effect. Finally, we describe the latest preclinical and clinical studies concerning the different pharmacological approaches targeting Notch.
  
  
  
  The provided evidence confirms the importance of Notch pathway in human malignancies indicating that a strong rationale exists for the development of a Notch-tailored therapy.
authors.affiliation: Department of Oncology and Hemato-Oncology, Universita degli Studi di Milano,via Festa del Perdono 7, I-20122, Milano,Italy.
authors.forename: Natalia
authors.initials: N
authors.lastname: Platonova
authors.affiliation: Department of Health Sciences, Universita degli Studi di Milano, via A. Di Rudini 8, I-20142, Milano, Italy.|Oncology Research group, Department of Health Sciences, Universita degli Studi di Milano, via A. Di Rudini 8, I-20142, Milano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Lesma
authors.affiliation: Department of Health Sciences, Universita degli Studi di Milano, via A. Di Rudini 8, I-20142, Milano, Italy.|Oncology Research group, Department of Health Sciences, Universita degli Studi di Milano, via A. Di Rudini 8, I-20142, Milano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Basile
authors.affiliation: Department of Health Sciences, Universita degli Studi di Milano, via A. Di Rudini 8, I-20142, Milano, Italy.|Oncology Research group, Department of Health Sciences, Universita degli Studi di Milano, via A. Di Rudini 8, I-20142, Milano, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Bignotto
authors.affiliation: Department of Health Sciences, Universita degli Studi di Milano, via A. Di Rudini 8, I-20142, Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Garavelli
authors.affiliation: Department of Health Sciences, Universita degli Studi di Milano, via A. Di Rudini 8, I-20142, Milano, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Palano
authors.affiliation: Department of Health Sciences, Universita degli Studi di Milano, via A. Di Rudini 8, I-20142, Milano, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Moschini
authors.affiliation: Department of Oncology and Hemato-Oncology, Universita degli Studi di Milano,via Festa del Perdono 7, I-20122, Milano,Italy.|Hematology, Fondazione Ca Granda IRCCS Policlinico, via F. Sforza, 35, 20122, Milano, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
authors.affiliation: Department of Health Sciences, Universita degli Studi di Milano, via A. Di Rudini 8, I-20142, Milano, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Colombo
authors.affiliation: Department of Health Sciences, Universita degli Studi di Milano, via A. Di Rudini 8, I-20142, Milano, Italy.|Oncology Research group, Department of Health Sciences, Universita degli Studi di Milano, via A. Di Rudini 8, I-20142, Milano, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Chiaramonte
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D051880:Receptors, Notch / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D051880:Receptors, Notch
keywords: Dll; Jagged; Notch; apoptosis; clinical trial; proliferation; therapeutic target