Abstract
Histone deacetylase inhibitors (HDACi) belong to a novel class of drugs able to act on the epigenome, indirectly remodeling the spatial conformation of the chromatin: by increasing histone acetylation these drugs ultimately promote the detachment of the DNA from the nucleosome octamer, therefore allowing the access of transcription factors to the double helix. Such a mechanism of action is of particular interest in the field of cancer treatment, considering the reactivation of silenced tumor suppressor genes as an important target at which aiming; indeed, it is currently believed that dysregulation of the epigenome plays a major role in cancer. Interestingly, some of the compounds belonging to the HDACi family have also additional therapeutic properties, as in the case of valproate that may ameliorate neuropathic pain in animal models and in patients. Conceivably, this is a remarkable observation, since peripheral neuropathy is a potentially severe side effect of several classes of anticancer agents, such as platinum-derived drugs, antitubulins or protesome inhibitors, limiting an effective treatment of the underlying cancer. Based on these data, in this review we will argue that, with respect to other nowadays available anticancer agents, HDACi might offer the advantage not only to target the neoplastic disorder, but also to prevent peripheral neuropathies, possibly displaying a complementary mechanism of action.
Keywords: Cisplatin, neuropathy, cancer, histones, valproate, neuroprotection
Current Cancer Drug Targets
Title: Targeting Cancer and Neuropathy with Histone Deacetylase Inhibitors:Two Birds with One Stone?
Volume: 8 Issue: 4
Author(s): V. Rodriguez-Menendez, L. Tremolizzo and G. Cavaletti
Affiliation:
Keywords: Cisplatin, neuropathy, cancer, histones, valproate, neuroprotection
Abstract: Histone deacetylase inhibitors (HDACi) belong to a novel class of drugs able to act on the epigenome, indirectly remodeling the spatial conformation of the chromatin: by increasing histone acetylation these drugs ultimately promote the detachment of the DNA from the nucleosome octamer, therefore allowing the access of transcription factors to the double helix. Such a mechanism of action is of particular interest in the field of cancer treatment, considering the reactivation of silenced tumor suppressor genes as an important target at which aiming; indeed, it is currently believed that dysregulation of the epigenome plays a major role in cancer. Interestingly, some of the compounds belonging to the HDACi family have also additional therapeutic properties, as in the case of valproate that may ameliorate neuropathic pain in animal models and in patients. Conceivably, this is a remarkable observation, since peripheral neuropathy is a potentially severe side effect of several classes of anticancer agents, such as platinum-derived drugs, antitubulins or protesome inhibitors, limiting an effective treatment of the underlying cancer. Based on these data, in this review we will argue that, with respect to other nowadays available anticancer agents, HDACi might offer the advantage not only to target the neoplastic disorder, but also to prevent peripheral neuropathies, possibly displaying a complementary mechanism of action.
Export Options
About this article
Cite this article as:
Rodriguez-Menendez V., Tremolizzo L. and Cavaletti G., Targeting Cancer and Neuropathy with Histone Deacetylase Inhibitors:Two Birds with One Stone?, Current Cancer Drug Targets 2008; 8 (4) . https://dx.doi.org/10.2174/156800908784533508
DOI https://dx.doi.org/10.2174/156800908784533508 |
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
-
Adverse Reactions Induced by Minocycline: A Review of Literature
Current Drug Safety Efficacy and Tolerability of Vinorelbine in the Cancer Therapy
Current Drug Safety Valproic Acid Metabolism and its Consequences on Sexual Functions
Current Drug Metabolism Acute Renal Failure in Different Malignant Tumors
Current Medicinal Chemistry Synthesis and Biochemical Evaluation of a Series of Methanesulfonate Derivatives of 4-Hydroxyphenyl Ketone as Probes of the Active Site of Type 3 OF 17β-Hydroxysteroid Dehydrogenase Family of Enzymes
Letters in Drug Design & Discovery Polymorphisms of Human N-Acetyltransferases and Cancer Risk
Current Drug Metabolism The Rational Design of Anticancer Platinum Complexes: The Importance of the Structure-Activity Relationship
Current Medicinal Chemistry The Characteristics, Functions and Inhibitors of Three Aminopeptidases Belonging to the M1 Family
Current Protein & Peptide Science Involvement of microRNA-146a in the Inflammatory Response of S tatus Epilepticus Rats
CNS & Neurological Disorders - Drug Targets Anti-Cancer Drugs of Today and Tomorrow: Are we Close to Making the Turn from Treating to Curing Cancer?
Current Pharmaceutical Design Cadmium and Its Epigenetic Effects
Current Medicinal Chemistry Decreased Expression and Altered Methylation of Syncytin-1 Gene in Human Placentas Associated with Preeclampsia
Current Pharmaceutical Design Drugs that Inhibit Tubulin Polymerization: The Particular Case of Podophyllotoxin and Analogues
Current Medicinal Chemistry - Anti-Cancer Agents The Voltammetric Determination of Bisphenol A Content of Polycarbonate Utensils Using a Resin Modified Carbon Paste Electrode
Current Physical Chemistry Aurora B: A New Prognostic Marker and Therapeutic Target in Cancer
Current Medicinal Chemistry Epigenetic Effects of Environmental Chemicals on Reproductive Biology
Current Drug Targets Patent Analysis as a Tool for Research Planning: Study on Natural Based Therapeutics Against Cancer Stem Cells
Recent Patents on Anti-Cancer Drug Discovery In Vitro Antitumoral Activity of Palladium(II) and Platinum(II) Complexes with O,O'-Dialkyl Esters of Ethylene-bis(S)-Leucine
Letters in Drug Design & Discovery Recent Developments in the Field of Tumor-Inhibiting Metal Complexes
Current Pharmaceutical Design Understanding the Interaction Between Human Serum Albumin and Anti-Bacterial/ Anti-Cancer Compounds
Current Pharmaceutical Design