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
-
Genetic Polymorphism and Tumor Immunotherapy
Current Pharmacogenomics Editorial: Looking Forward to Another Successful Year
Current Cancer Drug Targets Distribution, Bioactivities and Therapeutical Potentials of Pentagalloylglucopyranose
Current Bioactive Compounds Expression of Histone Acetyltransferase GCN5 and Histone Deacetylase 1 in the Cultured Mouse Preimplantation Embryos
Current Pharmaceutical Design Effects of Tyrosine Kinase Inhibitors on Growth and Bone Metabolism in Children with Haematologic Malignancies
Cardiovascular & Hematological Agents in Medicinal Chemistry Vybrant DyeCycle Violet Stain Discriminates Two Different Subsets of CD34+ Cells
Current Stem Cell Research & Therapy Recent Patents on Proteasome Inhibitors of Natural Origin
Recent Patents on Anti-Cancer Drug Discovery HSP90 Inhibitors: Multi-Targeted Antitumor Effects and Novel Combinatorial Therapeutic Approaches in Cancer Therapy
Current Medicinal Chemistry Melatonin Induces Apoptosis and Inhibits the Proliferation of Cancer Cells via Reactive Oxygen Species-mediated MAPK and mTOR Pathways
Clinical Cancer Drugs Are the Antioxidant Properties of Carvedilol Important for the Protection of Cardiac Mitochondria?
Current Vascular Pharmacology Two Promising Anti-Cancer Compounds, 2-Hydroxycinnaldehyde and 2- Benzoyloxycinnamaldehyde: Where do we stand?
Combinatorial Chemistry & High Throughput Screening MicroRNAs in Lymphoma: Regulatory Role and Biomarker Potential
Current Genomics Targeting Ion Channels in Leukemias: A New Challenge for Treatment
Current Medicinal Chemistry Targeting of Hsp32 in Solid Tumors and Leukemias: A Novel Approach to Optimize Anticancer Therapy (Supplementry Material)
Current Cancer Drug Targets MICA Molecules in Disease and Transplantation, a Double-Edged Sword?
Current Immunology Reviews (Discontinued) Therapeutic Potential of Adipose-derived Stem Cells in the Treatment of Pulmonary Diseases
Current Stem Cell Research & Therapy The Mevalonate Pathway as a Therapeutic Target in the Ph-Negative Chronic Myeloproliferative Disorders
Current Drug Targets Isolation of a New Sesquiterpene Lactone From Vernonia Zeylanica (L) Less and its Anti-Proliferative Effects in Breast Cancer Cell Lines
Anti-Cancer Agents in Medicinal Chemistry Cellular Uptake of Cell-Penetrating Peptides
Drug Design Reviews - Online (Discontinued) Higher Placental Anti-Inflammatory IL-10 Cytokine Expression in HIV-1 Infected Women Receiving Longer Zidovudine Prophylaxis Associated with Nevirapine
Current HIV Research