Abstract
Alterations in genomic and non-genomic mechanisms can disturb homeostasis and cause severe human diseases. Histone deacetylases (HDACs) are epigenetic regulators which catalyze the removal of acetyl moieties from histones and non-histone proteins. Aberrant histone deacetylation, due to increased HDAC activity and expression, often correlates with pathological gene repression and neoplastic transformation. Therefore, intense efforts have been made to find small molecule inhibitors of HDACs (HDACIs). Such compounds indeed alter cellular signaling networks relevant for tumorigenesis, and several HDACIs are currently tested in clinical trials against different types of cancer. Although HDACs share a conserved deacetylase domain and an at least similar mechanism of catalysis, isoenzyme-specific HDACIs could be identified and certain HDACIs even evoke degradation of HDACs. Here, we summarize molecular actions of HDACs and of different classes of HDACIs. In addition, we review data obtained in clinical studies involving HDACIs and we discuss how such agents might be beneficial for the treatment of cancer.
Keywords: Histone deacetylase, Histone deacetylase inhibitor, VPA, SAHA, cancer, chemotherapy, translational research, gene expression
Current Cancer Drug Targets
Title: Inhibitors of HDACs - Effective Drugs Against Cancer?
Volume: 10 Issue: 2
Author(s): S. Muller and O. H. Kramer
Affiliation:
Keywords: Histone deacetylase, Histone deacetylase inhibitor, VPA, SAHA, cancer, chemotherapy, translational research, gene expression
Abstract: Alterations in genomic and non-genomic mechanisms can disturb homeostasis and cause severe human diseases. Histone deacetylases (HDACs) are epigenetic regulators which catalyze the removal of acetyl moieties from histones and non-histone proteins. Aberrant histone deacetylation, due to increased HDAC activity and expression, often correlates with pathological gene repression and neoplastic transformation. Therefore, intense efforts have been made to find small molecule inhibitors of HDACs (HDACIs). Such compounds indeed alter cellular signaling networks relevant for tumorigenesis, and several HDACIs are currently tested in clinical trials against different types of cancer. Although HDACs share a conserved deacetylase domain and an at least similar mechanism of catalysis, isoenzyme-specific HDACIs could be identified and certain HDACIs even evoke degradation of HDACs. Here, we summarize molecular actions of HDACs and of different classes of HDACIs. In addition, we review data obtained in clinical studies involving HDACIs and we discuss how such agents might be beneficial for the treatment of cancer.
Export Options
About this article
Cite this article as:
Muller S. and H. Kramer O., Inhibitors of HDACs - Effective Drugs Against Cancer?, Current Cancer Drug Targets 2010; 10 (2) . https://dx.doi.org/10.2174/156800910791054149
DOI https://dx.doi.org/10.2174/156800910791054149 |
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
-
New Improved Drug Delivery Technologies for Pentacyclic Triterpenes: A Review
Protein & Peptide Letters Botulinum Toxin a in Prostate Disease: A Venom from Bench to Bed-Side
Current Drug Delivery Histone Lysine-Specific Methyltransferases and Demethylases in Carcinogenesis: New Targets for Cancer Therapy and Prevention
Current Cancer Drug Targets Vasculogenic and Angiogenic Pathways in Moyamoya Disease
Current Medicinal Chemistry Single-Photon Emission Computed Tomography Tracers for Predicting and Monitoring Cancer Therapy
Current Pharmaceutical Biotechnology Synthesis and Evaluation of Anti-Inflammatory and Antitussive Activity of Hydantion Derivatives
Letters in Drug Design & Discovery The Roles of Sox Family Genes in Sarcoma
Current Drug Targets Sigma-2 Receptor Ligands: Neurobiological Effects
Current Medicinal Chemistry Clinical, Immunological and Therapeutic Aspects of Autoimmune Encephalitis
Recent Patents on CNS Drug Discovery (Discontinued) Targeting the Atypical Chemokine Receptor ACKR3/CXCR7: Phase 1 - Phage Display Peptide Identification and Characterization
Current Topics in Medicinal Chemistry The Mechanisms of Anticancer Agents by Genistein and Synthetic Derivatives of Isoflavone
Mini-Reviews in Medicinal Chemistry Escape, or Vanish: Control the Fate of p53 through MDM2-Mediated Ubiquitination
Anti-Cancer Agents in Medicinal Chemistry Sentinel Lymph Node Mapping in Early Stage Endometrial Cancer Patients in Low-Resource Settings
Current Women`s Health Reviews How does the Selection of Laboratory Mice Affect the Results of Physiological Distribution of Radiopharmaceuticals?
Current Radiopharmaceuticals Metallic Colloid Nanotechnology, Applications in Diagnosis and Therapeutics
Current Pharmaceutical Design Bcl-2 Inhibitors: Emerging Drugs in Cancer Therapy
Current Medicinal Chemistry Lipids as Activators of Innate Immunity in Peptide Vaccine Delivery
Current Medicinal Chemistry Synthesis of pyridyl benzimidazoles encompassing 4-thiazolidinone derivatives as potential antimicrobial agents
Letters in Drug Design & Discovery Quality Survival with Fertility after Gynaecological and other Cancers
Current Women`s Health Reviews The Phosphoinositide 3-Kinase Pathway in Human Cancer: Genetic Alterations and Therapeutic Implications
Current Genomics