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
-
SYNTHESIS AND APPLICATIONS OF Fe3O4/SiO2 CORE-SHELL MATERIALS
Current Pharmaceutical Design Acute and Sub-chronic Toxicity Analyses of Hot-Water Extract of Isaria japonica from Silkworm (Bombyx mori) Pupae
Current Traditional Medicine In Situ Gene Therapy for Prostate Cancer
Current Gene Therapy Targeting Stem Cells-Clinical Implications for Cancer Therapy
Current Stem Cell Research & Therapy Phosphatidylinositol 3-Kinase Isoforms as Novel Drug Targets
Current Drug Targets Effects and Role of Multikinase Inhibitors in Thyroid Cancer
Current Pharmaceutical Design <i>In Silico</i> Study of Potential Cross-Kingdom Plant MicroRNA Based Regulation in Chronic Myeloid Leukemia
Current Pharmacogenomics and Personalized Medicine Lymphatic Delivery of Anti-HIV Drug Nanoparticles
Recent Patents on Nanotechnology The TGF-β Signaling Pathway as a Pharmacological Target in a Hepatocellular Carcinoma
Current Pharmaceutical Design Epidemiology of Candida albicans Infections and Role of Non-Candidaalbicans Yeasts
Current Drug Targets Interaction of Biologically Active Amines with Mitochondria and Their Role in the Mitochondrial-Mediated Pathway of Apoptosis
Current Medicinal Chemistry DYRK1A Kinase Inhibitors with Emphasis on Cancer
Mini-Reviews in Medicinal Chemistry Bench to Bedside Targeting of FLT3 in Acute Leukemia
Current Drug Targets Recent Advances in the Application of Podophyllotoxin Derivatives to Fight Against Multidrug-Resistant Cancer Cells
Current Topics in Medicinal Chemistry Peptide Vaccines for Cancer Therapy
Recent Patents on Inflammation & Allergy Drug Discovery Current Bioactive Azole-Containing Natural Products
Current Bioactive Compounds Combinatorial Protein Biochemistry for Therapeutics and Proteomics
Current Pharmaceutical Biotechnology Therapeutic Value of Black Seed Oil in Methotrexate Hepatotoxicity in Egyptian Children with Acute Lymphoblastic Leukemia
Infectious Disorders - Drug Targets New Therapies in SLE
Recent Patents on Inflammation & Allergy Drug Discovery “Non-Taxifolin” Derived Flavonolignans: Phytochemistry and Biology
Current Pharmaceutical Design