Abstract
Background: 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.
Methods: 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. Results: 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. Conclusion: 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.Keywords: Notch, Dll, Jagged, therapeutic target, clinical trial, apoptosis, proliferation.
Current Pharmaceutical Design
Title:Targeting Notch as a Therapeutic Approach for Human Malignancies
Volume: 23 Issue: 1
Author(s): Natalia Platonova, Elena Lesma, Andrea Basile, Monica Bignotto, Silvia Garavelli, Maria Teresa Palano, Adriana Moschini, Antonino Neri, Michela Colombo and Raffaella Chiaramonte
Affiliation:
Keywords: Notch, Dll, Jagged, therapeutic target, clinical trial, apoptosis, proliferation.
Abstract: Background: 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.
Methods: 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. Results: 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. Conclusion: 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.Export Options
About this article
Cite this article as:
Platonova Natalia, Lesma Elena, Basile Andrea, Bignotto Monica, Garavelli Silvia, Palano Teresa Maria, Moschini Adriana, Neri Antonino, Colombo Michela and Chiaramonte Raffaella, Targeting Notch as a Therapeutic Approach for Human Malignancies, Current Pharmaceutical Design 2017; 23 (1) . https://dx.doi.org/10.2174/1381612822666161006160524
DOI https://dx.doi.org/10.2174/1381612822666161006160524 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The JAK-STAT Pathway: A Therapeutic Target in Hematological Malignancies
Current Cancer Drug Targets Targeting the RAS Signaling Pathway in Malignant Hematologic Diseases
Current Drug Targets CypA: A Potential Target of Tumor Radiotherapy and/or Chemotherapy
Current Medicinal Chemistry Evolving Strategies for the Treatment of T-Cell Lymphoma: A Systematic Review and Recent Patents
Recent Patents on Anti-Cancer Drug Discovery Molecular Advances Toward the Understanding of the Patho-Biology of Idiopathic Myelofibrosis
Current Immunology Reviews (Discontinued) Recent Advances in the Imaging of Programmed Cell Death
Current Pharmaceutical Design Adverse Effects and Drug Interactions of Biologic Agents
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Editorial [ Hot Topic: Highlights on Important Signaling Pathways as Drug Targets in Hematological Malignancies (Guest Editors: H. Serve and H.C. Hasselbalch) ]
Current Drug Targets Bortezomib in the Treatment of Cancer
Recent Patents on Anti-Cancer Drug Discovery Vascular Targeting: A New Antitumor Activity
Drug Design Reviews - Online (Discontinued) The p38α Kinase Plays a Central Role In Inflammation
Current Topics in Medicinal Chemistry Monoclonal Antibodies in the Treatment of Hematologic Malignancies: Radiation Dosimetry Aspects
Current Pharmaceutical Biotechnology Receptor Tyrosine Kinases as Target for Anti-Cancer Therapy
Current Pharmaceutical Design Busulfan Use in Hematopoietic Stem Cell Transplantation: Pharmacology, Dose Adjustment, Safety and Efficacy in Adults and Children
Current Drug Safety Prostate Cancer Horizons in the Development of Novel Anti-Cancer Strategies
Current Medicinal Chemistry - Anti-Cancer Agents Parallel Gene Expression Profiling of Mantle Cell Lymphoma – How Do We Transform ´Omics Data into Clinical Practice
Current Genomics Telomerase Modulation in Therapeutic Approach
Current Pharmaceutical Design Specific Hemosiderin Deposition in Spleen Induced by a Low Dose of Cisplatin: Altered Iron Metabolism and Its Implication as an Acute Hemosiderin Formation Model
Current Drug Metabolism Novel Molecular-Targeted Therapeutics for the Treatment of Cancer
Anti-Cancer Agents in Medicinal Chemistry The Leukocyte Common Antigen-Related Protein LAR: Candidate PTP for Inhibitory Targeting
Current Topics in Medicinal Chemistry