Abstract
NOTCH-ligand interaction is a highly conserved mechanism that regulates specific cell fate decision during development. In addition to its functions in developmental and cell maturation processes, studies indicate that NOTCH activation plays a role in the onset and progression of many human malignancies. The prevailing new strategy for rationally targeted cancer treatment is aimed at the development of targetselective “ smart ” drugs on the basis of characterized mechanisms of action. The connection between NOTCH signaling and tumorigenesis suggests that NOTCH may be such a target candidate. Gamma-secretase is a large membrane-integral multisubunit protease complex, which is essential for NOTCH receptor activation. Inhibitors of this enzyme are being developed for Alzheimer ’ s disease, due to its role in cleaving beta-amyloid precursor in the brain. Recently, Gamma-secretase inhibitors (GSIs), as well as various biopharmaceutical or genetic NOTCH signaling inhibitors have been suggested as potential novel cancer therapeutic strategies. This review summarizes the evidence linking NOTCH signaling to several types of cancer, as well as the possible therapeutic indications of NOTCH inhibitors and the challenges facing their clinical development.
Keywords: NOTCH, cancer experimental therapy, Gamma-Secretase
Current Cancer Drug Targets
Title: NOTCH Signaling as a Novel Cancer Therapeutic Target
Volume: 6 Issue: 4
Author(s): L. Miele, H. Miao and B. J. Nickoloff
Affiliation:
Keywords: NOTCH, cancer experimental therapy, Gamma-Secretase
Abstract: NOTCH-ligand interaction is a highly conserved mechanism that regulates specific cell fate decision during development. In addition to its functions in developmental and cell maturation processes, studies indicate that NOTCH activation plays a role in the onset and progression of many human malignancies. The prevailing new strategy for rationally targeted cancer treatment is aimed at the development of targetselective “ smart ” drugs on the basis of characterized mechanisms of action. The connection between NOTCH signaling and tumorigenesis suggests that NOTCH may be such a target candidate. Gamma-secretase is a large membrane-integral multisubunit protease complex, which is essential for NOTCH receptor activation. Inhibitors of this enzyme are being developed for Alzheimer ’ s disease, due to its role in cleaving beta-amyloid precursor in the brain. Recently, Gamma-secretase inhibitors (GSIs), as well as various biopharmaceutical or genetic NOTCH signaling inhibitors have been suggested as potential novel cancer therapeutic strategies. This review summarizes the evidence linking NOTCH signaling to several types of cancer, as well as the possible therapeutic indications of NOTCH inhibitors and the challenges facing their clinical development.
Export Options
About this article
Cite this article as:
Miele L., Miao H. and Nickoloff J. B., NOTCH Signaling as a Novel Cancer Therapeutic Target, Current Cancer Drug Targets 2006; 6 (4) . https://dx.doi.org/10.2174/156800906777441771
DOI https://dx.doi.org/10.2174/156800906777441771 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
Related Articles
-
One Hundred Faces of Cyclopamine
Current Pharmaceutical Design Protein Kinase C and Prostate Carcinogenesis: Targeting the Cell Cycle and Apoptotic Mechanisms
Current Drug Targets Impact of RET Screening on the Management of Multiple Endocrine Neoplasia Type 2A: 10 Years Experience and Follow-Up in Three Families
Endocrine, Metabolic & Immune Disorders - Drug Targets Targeting the Hedgehog Pathway for Locally Advanced and Metastatic Basal Cell Carcinoma
Current Pharmaceutical Design Acetylcholinesterase Enzyme Inhibitor Molecules with Therapeutic Potential for Alzheimer's Disease
CNS & Neurological Disorders - Drug Targets Future Developments in Osteoporosis Therapy
Endocrine, Metabolic & Immune Disorders - Drug Targets Bone Seeking Radiopharmaceuticals for Palliation of Pain in Cancer Patients with Osseous Metastases
Anti-Cancer Agents in Medicinal Chemistry Angiogenesis and Metastasis Inhibitors for the Treatment of Malignant Melanoma
Mini-Reviews in Medicinal Chemistry p53-Induced Apoptosis and Inhibitors of p53
Current Medicinal Chemistry Soluble Adhesion Molecules in the Pathogenesis of Rheumatoid Arthritis
Current Pharmaceutical Design Ghrelin and Motilin in the Gastrointestinal System
Current Pharmaceutical Design Hypoxia and Fetal Heart Development
Current Molecular Medicine Multidrug Transporters as Drug Targets
Current Drug Targets The Quest for Novel Biomarkers in Early Diagnosis of Diabetic Neuropathy
Current Proteomics Axin PPI Networks: New Interacting Proteins and New Targets?
Current Topics in Medicinal Chemistry Development of Anti-Atherosclerosis Therapy Based on the Inflammatory and Proliferative Aspects of the Disease
Current Pharmaceutical Design Monoclonal Antobodies: Application in Radiopharmacy
Current Radiopharmaceuticals Epidermolysis Bullosa: Pediatric Perspectives
Current Pediatric Reviews Peptides Targeting Estrogen Receptor Alpha-Potential Applications for Breast Cancer Treatment
Current Pharmaceutical Design Signal Transduction Abnormalities in Suicide: Focus on Phosphoinositide Signaling System
CNS & Neurological Disorders - Drug Targets