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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
- 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
-
PET with Non-Standard Nuclides
Current Topics in Medicinal Chemistry Carbon Nanotubes: An Emerging Drug Delivery Carrier in Cancer Therapeutics
Current Drug Delivery Mitochondrial Drug Targets in Cell Death and Cancer
Current Pharmaceutical Design Synthesis of Bacteriochlorins and Their Potential Utility in Photodynamic Therapy (PDT)
Current Organic Chemistry Targeted Tumor Therapies at a Glance
Current Drug Targets Radionuclide Liver Cancer Therapies: From Concept to Current Clinical Status
Anti-Cancer Agents in Medicinal Chemistry Potential Role of <i>In Vitro-In Vivo</i> Correlations (IVIVC) for the Development of Plant-Derived Anticancer Drugs
Current Drug Targets Probiotics as an Alternative Strategy for Prevention and Treatment of Human Diseases: A Review
Inflammation & Allergy - Drug Targets (Discontinued) An Overview of Acute Flaccid Myelitis
CNS & Neurological Disorders - Drug Targets Therapeutic Applications of Crocus sativus L. (Saffron): A Review
The Natural Products Journal MicroRNAs and Cancer: Towards a Personalized Medicine
Current Molecular Medicine Epidemiology and Prevention of Bacterial Infections in Patients with Hematologic Malignancies
Infectious Disorders - Drug Targets Ketamine as Antidepressant? Current State and Future Perspectives
Current Neuropharmacology Conjugates of Natural Compounds with Nitroxyl Radicals as a Basis for Creation of Pharmacological Agents of New Generation
Current Medicinal Chemistry The Pleiotropic Effects of Inducible Nitric Oxide Synthase (iNOS) on the Physiology and Pathology of Penile Erection
Current Pharmaceutical Design Extrahepatic Targets and Cellular Reactivity of Drug Metabolites
Current Medicinal Chemistry HtrA Serine Proteases as Potential Therapeutic Targets in Cancer
Current Cancer Drug Targets Infection, Infectious Agents and Vascular Disease
Reviews on Recent Clinical Trials Blind Snipers: Relevant Off Target Effects of Non-chemotherapeutic Agents in Oncology: Review of the Literature
Reviews on Recent Clinical Trials Transient Receptor Potential Vanilloid 1 Channel Modulation: A Novel Approach to Pain Therapy
Current Bioactive Compounds