Abstract
The ability to inhibit kinases such as Bcr-Abl, Her2, Flt3, and the epidermal growth factor receptor has ushered in a new generation of targeted therapies, based on the unique molecular abnormalities present in tumor cells. However, activation of most of these kinases is found in only a small fraction of tumors. In most cancers, a variety of kinases may become activated, but the malignant phenotype of a cell is driven through the downstream activation of a relatively small number of transcription factors. One family of transcription factors found to be activated in a wide spectrum of human cancers is the signal transducers and activators of transcription, or STATs. In tumor systems, STAT inhibition has been shown to decrease cellular proliferation and lower the threshold for apoptosis. By contrast, inhibition of STATs in normal tissue is generally well tolerated, presumably due to the presence of complementary or redundant signaling pathways. With increased knowledge regarding the molecular steps in the activation of STATs and other transcription factors, very specific inhibitors can be designed and synthesized. Hence, either alone or in combination with targeted or cytotoxic therapies, inhibition of STATs and other transcription factors may be a powerful new approach towards cancer therapy.
Keywords: Signal transduction, molecular oncology, protein phosphorylation
Current Cancer Therapy Reviews
Title: STAT Inhibition in the Treatment of Cancer: Transcription Factors as Targets for Molecular Therapy
Volume: 2 Issue: 1
Author(s): David A. Frank
Affiliation:
Keywords: Signal transduction, molecular oncology, protein phosphorylation
Abstract: The ability to inhibit kinases such as Bcr-Abl, Her2, Flt3, and the epidermal growth factor receptor has ushered in a new generation of targeted therapies, based on the unique molecular abnormalities present in tumor cells. However, activation of most of these kinases is found in only a small fraction of tumors. In most cancers, a variety of kinases may become activated, but the malignant phenotype of a cell is driven through the downstream activation of a relatively small number of transcription factors. One family of transcription factors found to be activated in a wide spectrum of human cancers is the signal transducers and activators of transcription, or STATs. In tumor systems, STAT inhibition has been shown to decrease cellular proliferation and lower the threshold for apoptosis. By contrast, inhibition of STATs in normal tissue is generally well tolerated, presumably due to the presence of complementary or redundant signaling pathways. With increased knowledge regarding the molecular steps in the activation of STATs and other transcription factors, very specific inhibitors can be designed and synthesized. Hence, either alone or in combination with targeted or cytotoxic therapies, inhibition of STATs and other transcription factors may be a powerful new approach towards cancer therapy.
Export Options
About this article
Cite this article as:
Frank A. David, STAT Inhibition in the Treatment of Cancer: Transcription Factors as Targets for Molecular Therapy, Current Cancer Therapy Reviews 2006; 2 (1) . https://dx.doi.org/10.2174/157339406775471803
DOI https://dx.doi.org/10.2174/157339406775471803 |
Print ISSN 1573-3947 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6301 |
Call for Papers in Thematic Issues
Current progress in Protein Degradation and Cancer Therapy
argeted Protein Degradation is gaining momentum in cancer therapy, it facilitate targeting undruggable proteins, it overcome cancer resistance and avoid undesirable side effects. Thus small molecules degraders have emerged as novel therapeutic strategy. Targeted protein degradation (TPD), the process of eliminating a protein of interest hold a great promise for ...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
-
Production, Novel Assay Development and Clinical Applications of Monoclonal Antibodies
Recent Patents on Anti-Cancer Drug Discovery Polysaccharide Colloids as Smart Vehicles in Cancer Therapy
Current Pharmaceutical Design The Functions of Heparanase in Human Diseases
Mini-Reviews in Medicinal Chemistry Advances in Tumor Targeted Liposomes
Current Molecular Medicine Chalcones in Cancer: Understanding their Role in Terms of QSAR. II Part
Mini-Reviews in Medicinal Chemistry Targeting the Acute Myeloid Leukemia Stem Cells
Anti-Cancer Agents in Medicinal Chemistry Epidemiology and Management of Infectious Complications in Contemporary Management of Chronic Leukemias
Infectious Disorders - Drug Targets Clinical Pharmacogenetics of Methotrexate
Current Drug Metabolism GSK-3 Inhibitors: Discoveries and Developments
Current Medicinal Chemistry Specific Immune Intervention with Monoclonal Antibodies for the Treatment of Multiple Sclerosis
Current Medicinal Chemistry Ribonucleotide Reductase: A Mechanistic Portrait of Substrate Analogues Inhibitors
Current Medicinal Chemistry The Contractile Properties of Airway Smooth Muscle: How their Defects can be Linked to Asthmatic Airway Hyperresponsiveness?
Current Respiratory Medicine Reviews Antibody Engineering, Virus Retargeting and Cellular Immunotherapy: One Ring to Rule Them All?
Current Gene Therapy Redox-active and Redox-silent Compounds: Synergistic Therapeutics in Cancer
Current Medicinal Chemistry Histone Deacetylase Inhibitors: A Review on Class-I Specific Inhibition
Mini-Reviews in Medicinal Chemistry Cytosine Methyltransferases as Tumor Markers
Current Genomics In or Out Stemness: Comparing Growth Factor Signalling in Mouse Embryonic Stem Cells and Primordial Germ Cells
Current Stem Cell Research & Therapy Retrovirus Translation Initiation: Issues and Hypotheses Derived from Study of HIV-1
Current HIV Research Modulation of Huntington’s Disease in Drosophila
CNS & Neurological Disorders - Drug Targets Unleashing the Guardian: The Targetable BCR-ABL/HAUSP/PML/PTEN Network in Chronic Myeloid Leukemia
Current Drug Targets