Abstract
The histone deacetylase inhibitors are a new class of cytostatic agents that inhibit the proliferation of tumor cells in culture and in vivo by inducing cell cycle arrest, differentiation and / or apoptosis. Histone acetylation and deacetylation play important roles in the modulation of chromatin topology and the regulation of gene transcription. Histone deacetylase inhibition induces the accumulation of hyperacetylated nucleosome core histones in most regions of chromatin but affects the expression of only a small subset of genes, leading to transcriptional activation of some genes, but repression of an equal or larger number of other genes. Non-histone proteins such as transcription factors are also targets for acetylation with varying functional effects. Acetylation enhances the activity of some transcription factors such as the tumor suppressor p53 and the erythroid differentiation factor GATA-1 but may repress transcriptional activity of others including T cell factor and the co-activator ACTR. Recent studies in our laboratory and others have shown that the estrogen receptor α (ERα) can be hyperacetylated in response to histone deacetylase inhibition, suppressing ligand sensitivity and regulating transcriptional activation by histone deacetylase inhibitors. Conservation of the acetylated ERα motif in other nuclear receptors suggests that acetylation may play an important regulatory role in diverse nuclear receptor signaling functions. A number of structurally diverse histone deacetylase inhibitors have shown potent antitumor efficacy with little toxicity in vivo in animal models. Several compounds are currently in early phase clinical development as potential treatments for solid and hematological cancers both as monotherapy and in combination with cytotoxics and differentiation agents. This report reviews the biology and clinical development of histone deacetylase inhibitors for cancer therapy.
Keywords: cytostatic, deacetylase, monotherapy, hematological, histone
Current Cancer Drug Targets
Title: Targeted Histone Deacetylase Inhibition for Cancer Therapy
Volume: 4 Issue: 2
Author(s): D. M. Vigushin and R. C. Coombes
Affiliation:
Keywords: cytostatic, deacetylase, monotherapy, hematological, histone
Abstract: The histone deacetylase inhibitors are a new class of cytostatic agents that inhibit the proliferation of tumor cells in culture and in vivo by inducing cell cycle arrest, differentiation and / or apoptosis. Histone acetylation and deacetylation play important roles in the modulation of chromatin topology and the regulation of gene transcription. Histone deacetylase inhibition induces the accumulation of hyperacetylated nucleosome core histones in most regions of chromatin but affects the expression of only a small subset of genes, leading to transcriptional activation of some genes, but repression of an equal or larger number of other genes. Non-histone proteins such as transcription factors are also targets for acetylation with varying functional effects. Acetylation enhances the activity of some transcription factors such as the tumor suppressor p53 and the erythroid differentiation factor GATA-1 but may repress transcriptional activity of others including T cell factor and the co-activator ACTR. Recent studies in our laboratory and others have shown that the estrogen receptor α (ERα) can be hyperacetylated in response to histone deacetylase inhibition, suppressing ligand sensitivity and regulating transcriptional activation by histone deacetylase inhibitors. Conservation of the acetylated ERα motif in other nuclear receptors suggests that acetylation may play an important regulatory role in diverse nuclear receptor signaling functions. A number of structurally diverse histone deacetylase inhibitors have shown potent antitumor efficacy with little toxicity in vivo in animal models. Several compounds are currently in early phase clinical development as potential treatments for solid and hematological cancers both as monotherapy and in combination with cytotoxics and differentiation agents. This report reviews the biology and clinical development of histone deacetylase inhibitors for cancer therapy.
Export Options
About this article
Cite this article as:
Vigushin M. D. and Coombes C. R., Targeted Histone Deacetylase Inhibition for Cancer Therapy, Current Cancer Drug Targets 2004; 4 (2) . https://dx.doi.org/10.2174/1568009043481560
DOI https://dx.doi.org/10.2174/1568009043481560 |
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
-
Recent Advancemnts in Biodegradable Ocular Implants
Current Drug Delivery Kinetic Evaluation of Anti-tumor Chlorambucil Release from O-stearoyl Mannose PLGA Nanoparticles
Current Nanomedicine Protein disulfide isomerase and Nox: new partners in redox signaling
Current Pharmaceutical Design Novel Marine and Microbial Natural Product Inhibitors of Vacuolar ATPase
Current Medicinal Chemistry Antigen-specific Immunotherapy in Ovarian Cancer and p53 as Tumor Antigen
Current Pharmaceutical Design Performance Identification Using Morphological Approach on Digital Mammographic Images
Current Signal Transduction Therapy Data Science Approaches to Pharmacogenetics
Current Molecular Medicine Immunological Approaches to Prevent Neuronal Apoptosis During Neuroinflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents A Scientific Approach to Anti-Ageing Therapies: State of the Art
Current Pharmaceutical Design Role of microRNA Deregulation in Breast Cancer Cell Chemoresistance and Stemness
Current Medicinal Chemistry Preparation and Characterization of Nanoemulsome Entrapped in Enteric Coated Hydrogel Beads for the Controlled Delivery of Capsaicin to the Colon
Current Drug Therapy Clinical Pharmacology of Trastuzumab
Current Clinical Pharmacology Design, Synthesis and Biological Evaluation of Palladium (II) Complexes with 1-(substituted benzyl) azetidine-3,3-dicarboxylates as Leaving Group
Medicinal Chemistry HPV Infections: Basis of Neoplastic Transformation and Related Molecular Tests
Current Pharmaceutical Design Clinical Pharmacogenetics and Potential Application in Personalized Medicine
Current Drug Metabolism Association of Genetic Variants with Colorectal Cancer in the Extended MENA Region: A Systematic Review
Current Molecular Medicine Bioinformatics Analysis based on Multiple Databases Identifies Hub Genes Associated with Hepatocellular Carcinoma
Current Genomics The Use of HepaRG and Human Hepatocyte Data in Predicting CYP Induction Drug-Drug Interactions via Static Equation and Dynamic Mechanistic Modelling Approaches
Current Drug Metabolism Genetic Alterations in Poorly Differentiated and Undifferentiated Thyroid Carcinomas
Current Genomics Metabolic Syndrome in HIV-patients in Antiretroviral Therapy
Current HIV Research