Abstract
Histone deacetylases (HDACs) influence diverse cellular processes and may contribute to tumor development and progression by multiple mechanisms. Class I HDACs are often overexpressed in cancers contributing to a genome-wide epigenetic state permitting increased proliferation, and diminished apoptosis and cell differentiation. Class IIA and IIB isoenzymes may likewise contribute to tumorigenesis as components of specific intranuclear repressor complexes or regulators of posttranslational protein modifications. As HDAC inhibitors may counteract these tumorigenic effects several of these compounds are currently tested in clinical trials.
HDAC inhibitors are also considered for urothelial carcinoma, where novel therapeutic drugs are urgently required. However, only modest antineoplastic activity has been observed with isoenzyme-unspecific pan-HDAC inhibitors. Therefore, inhibition of specific HDAC isoenzymes might be more efficacious and tumor-specific. Here, we systematically review knowledge on the expression, function and suitability as therapeutic targets of the 11 classical HDACs in UC. Overall, the class I HDACs HDAC1 and HDAC2 are the most promising targets for antineoplastic treatment. In contrast, targeting HDAC8 and HDAC6 is likely to be of minor relevance in urothelial carcinoma. Class IIA HDACs like HDAC4 require further study, since their downregulation rather than upregulation could be involved in urothelial carcinoma pathogenesis.
Keywords: Urothelial carcinoma, bladder cancer, HDACSs, HDAC inhibitors, class I HDACs, targeted therapy.
Current Medicinal Chemistry
Title:HDACs and HDAC Inhibitors in Urothelial Carcinoma – Perspectives for an Antineoplastic Treatment
Volume: 24 Issue: 37
Author(s): Maria Pinkerneil, Michele J. Hoffmann, Wolfgang A. Schulz and Gunter Niegisch*
Affiliation:
- Department of Urology, Medical Faculty, Heinrich-Heine-University, Dusseldorf,Germany
Keywords: Urothelial carcinoma, bladder cancer, HDACSs, HDAC inhibitors, class I HDACs, targeted therapy.
Abstract: Histone deacetylases (HDACs) influence diverse cellular processes and may contribute to tumor development and progression by multiple mechanisms. Class I HDACs are often overexpressed in cancers contributing to a genome-wide epigenetic state permitting increased proliferation, and diminished apoptosis and cell differentiation. Class IIA and IIB isoenzymes may likewise contribute to tumorigenesis as components of specific intranuclear repressor complexes or regulators of posttranslational protein modifications. As HDAC inhibitors may counteract these tumorigenic effects several of these compounds are currently tested in clinical trials.
HDAC inhibitors are also considered for urothelial carcinoma, where novel therapeutic drugs are urgently required. However, only modest antineoplastic activity has been observed with isoenzyme-unspecific pan-HDAC inhibitors. Therefore, inhibition of specific HDAC isoenzymes might be more efficacious and tumor-specific. Here, we systematically review knowledge on the expression, function and suitability as therapeutic targets of the 11 classical HDACs in UC. Overall, the class I HDACs HDAC1 and HDAC2 are the most promising targets for antineoplastic treatment. In contrast, targeting HDAC8 and HDAC6 is likely to be of minor relevance in urothelial carcinoma. Class IIA HDACs like HDAC4 require further study, since their downregulation rather than upregulation could be involved in urothelial carcinoma pathogenesis.
Export Options
About this article
Cite this article as:
Pinkerneil Maria, Hoffmann J. Michele, Schulz A. Wolfgang and Niegisch Gunter*, HDACs and HDAC Inhibitors in Urothelial Carcinoma – Perspectives for an Antineoplastic Treatment, Current Medicinal Chemistry 2017; 24 (37) . https://dx.doi.org/10.2174/0929867324666170207142740
DOI https://dx.doi.org/10.2174/0929867324666170207142740 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
- Announcements
Related Articles
-
Recent Developments in Targeted Therapies of the RAF-MEK and PI3KAKT Pathways in Cancer Treatment
Current Cancer Therapy Reviews Management of Antineutrophil Cytoplasmic Antibody Associated Vasculitis
Current Immunology Reviews (Discontinued) Deregulation of PI3K/Akt/mTOR Signaling Pathways by Isoflavones and its Implication in Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Genetic Engineering - A New Era for Cancer Immunotherapy?
Current Cancer Therapy Reviews Tumor-Targeting Peptides and Small Molecules as Anti-Cancer Agents to Overcome Drug Resistance
Current Medicinal Chemistry Receptor Mediated Tumor Targeting: An Emerging Approach for Cancer Therapy
Current Drug Delivery A Role for the Inflammatory Mediators Cox-2 and Metalloproteinases in Cancer Stemness
Anti-Cancer Agents in Medicinal Chemistry Diabetes and Its Complications: Therapies Available, Anticipated and Aspired
Current Diabetes Reviews Engineered Nanoparticles for Improved Vasoactive Intestinal Peptide (VIP) Biomedical Applications
Recent Patents on Nanomedicine Genistein as a Potential Anticancer Agent Against Head and Neck Squamous Cell Carcinoma
Current Topics in Medicinal Chemistry Nanoparticle-Based Combination Therapy for Cancer Treatment
Current Pharmaceutical Design The Significance of Transferrin Receptors in Oncology: the Development of Functional Nano-based Drug Delivery Systems
Current Drug Delivery The Pathogenic Role of Intestinal Flora in IBD and Colon Cancer
Current Drug Targets Critical Roles of EGFR Family Members in Breast Cancer and Breast Cancer Stem Cells: Targets for Therapy
Current Pharmaceutical Design Purinergic Signalling: What is Missing and Needed Next? The Use of Transgenic Mice, Crystallographic Analysis and MicroRNA
CNS & Neurological Disorders - Drug Targets Alzheimer’s Disease and Environmental Exposure to Lead: The Epidemiologic Evidence and Potential Role of Epigenetics
Current Alzheimer Research Inhibition of Human 5-Lipoxygenase and Anti-Neoplastic Effects by 2-Amino-1,4-Benzoquinones
Medicinal Chemistry Valproic Acid As Anti-Cancer Drug
Current Pharmaceutical Design Patent Selections
Recent Patents on Biomedical Engineering (Discontinued) Cathepsin D as a Promising Target for the Discovery of Novel Anticancer Agents
Current Cancer Drug Targets