Abstract
Epigenetics as well as post-translational modifications of proteins are emerging as novel attractive targets for anti-cancer therapy. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are two classes of enzymes regulating histone acetylation and whose altered activity has been identified in several cancers. In particular, imbalance in histone acetylation can lead to changes in chromatin structure and transcriptional dysregulation of genes that are involved in the control of proliferation, cell-cycle progression, differentiation and/or apoptosis. In addition, several non histone protein substrates such as transcription factors, chaperone proteins or tubulin, undergo acetylation as key post-translation modification regulating their half-life and function. On this regard, several inhibitors of HDAC, selected by academic as well as industrial research, have been recently shown to induce growth arrest and apoptosis in a variety of human cancer cells and have been patented as anti-cancer agents. Although several clinical studies with HDAC inhibitors are ongoing, their mechanism of action cannot be solely attributed to the level of histone acetylation and molecular basis for their tumor selectivity remains unknown, presenting a challenge for the cancer research community.
Keywords: Histone deacetylase, histone deacetylase inhibitors, combination therapy, cancer
Recent Patents on Anti-Cancer Drug Discovery
Title: Histone Deacetylase Inhibitors: A New Wave of Molecular Targeted Anticancer Agents
Volume: 2 Issue: 2
Author(s): Alfredo Budillon, Elena Di Gennaro, Francesca Bruzzese, Monia Rocco, Giuseppe Manzo and Michele Caraglia
Affiliation:
Keywords: Histone deacetylase, histone deacetylase inhibitors, combination therapy, cancer
Abstract: Epigenetics as well as post-translational modifications of proteins are emerging as novel attractive targets for anti-cancer therapy. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are two classes of enzymes regulating histone acetylation and whose altered activity has been identified in several cancers. In particular, imbalance in histone acetylation can lead to changes in chromatin structure and transcriptional dysregulation of genes that are involved in the control of proliferation, cell-cycle progression, differentiation and/or apoptosis. In addition, several non histone protein substrates such as transcription factors, chaperone proteins or tubulin, undergo acetylation as key post-translation modification regulating their half-life and function. On this regard, several inhibitors of HDAC, selected by academic as well as industrial research, have been recently shown to induce growth arrest and apoptosis in a variety of human cancer cells and have been patented as anti-cancer agents. Although several clinical studies with HDAC inhibitors are ongoing, their mechanism of action cannot be solely attributed to the level of histone acetylation and molecular basis for their tumor selectivity remains unknown, presenting a challenge for the cancer research community.
Export Options
About this article
Cite this article as:
Alfredo Budillon , Elena Di Gennaro , Francesca Bruzzese , Monia Rocco , Giuseppe Manzo and Michele Caraglia , Histone Deacetylase Inhibitors: A New Wave of Molecular Targeted Anticancer Agents, Recent Patents on Anti-Cancer Drug Discovery 2007; 2 (2) . https://dx.doi.org/10.2174/157489207780832450
DOI https://dx.doi.org/10.2174/157489207780832450 |
Print ISSN 1574-8928 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3970 |
Call for Papers in Thematic Issues
Novel anti-cancer drugs in photoimmunotherapy management: from bench to translational research
In recent years, traditional cancer treatments, such as surgery, chemotherapy, and radiation treatment, etc., may damage the pathological tissue and normal cells. The ideal tumor treatment should be noninvasive, eliminating the primary tumor, making the body produce systemic tumor-specific immunity, eliminating metastases, and having less /no side effects. Recent Patents ...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
-
Biomarkers of Aging with Prognostic and Predictive Value in Non-Oncological Diseases
Current Medicinal Chemistry Cell Metabolism Under Microenvironmental Low Oxygen Tension Levels in Stemness, Proliferation and Pluripotency
Current Molecular Medicine Addressing the Challenge: Current and Future Directions in Ovarian Cancer Therapy
Current Gene Therapy High-Risk HPV/ErbB-2 Interaction on E-Cadherin/Catenin Regulation in Human Carcinogenesis
Current Pharmaceutical Design Relevance of Drug Metabolizing Enzyme Activity Modulation by Tea Polyphenols in the Inhibition of Esophageal Tumorigenesis
Medicinal Chemistry Bothrops pauloensis Snake Venom Toxins: The Search for New Therapeutic Models
Current Topics in Medicinal Chemistry Radioprotective Gene Therapy
Current Gene Therapy Cytochrome P450 2A6 Phenotyping Using Dietary Caffeine Salivary Metabolite Ratios and Genotyping Using Blood on Storage Cards in Non-smoking Japanese Volunteers
Drug Metabolism Letters Salinomycin Suppresses Tumorigenicity of Liver Cancer Stem Cells and Wnt/Beta-catenin Signaling
Current Stem Cell Research & Therapy E-Cadherin Upregulation as a Therapeutic Goal in Cancer Treatment
Mini-Reviews in Medicinal Chemistry Mitochondrial Respiratory Complex I: Structure, Function and Implication in Human Diseases
Current Medicinal Chemistry Isoprenylation of Intracellular Proteins as a New Target for the Therapy of Human Neoplasms: Preclinical and Clinical Implications
Current Drug Targets Pharmacokinetic and Pharmacodynamic Variability: A Daunting Challenge in Drug Therapy
Current Drug Metabolism Bioactive Triterpenic Acids: From Agroforestry Biomass Residues to Promising Therapeutic Tools
Mini-Reviews in Organic Chemistry Alveolar Epithelial Stem and Progenitor Cells: Emerging Evidence for their Role in Lung Regeneration
Current Medicinal Chemistry Sp/KLF Family and Tumor Angiogenesis in Pancreatic Cancer
Current Pharmaceutical Design Linking Inflammation to Cell Cycle Progression
Current Pharmaceutical Design Molecular Imaging in Optical Coherence Tomography
Current Molecular Imaging (Discontinued) Targeted Inhibition of Rictor/mTORC2 in Cancer Treatment: A New Era after Rapamycin
Current Cancer Drug Targets Update on COX-2 Selective Inhibitors: Chemical Classification, Side Effects and their Use in Cancers and Neuronal Diseases
Current Topics in Medicinal Chemistry