Abstract
Although chemotherapy is considered the mainstay of cancer therapy, unfortunate side effects of chemotherapy create a continuous demand for developing other novel and specific targets for cancer therapy. Re-expression of epigenetically silenced tumor suppressor genes is a rational strategy for the treatment of human neoplasms. Epigenetic modifiers like DNA methyltransferase (DNMT) inhibitors and histone deacteylase (HDAC) inhibitors induce the re-expression of epigenetically silenced genes in vitro and in vivo. Moreover, they demonstrate safety and efficacy against neoplastic diseases in clinical trials. DNMT inhibitors like 5-azacytidine and 5-aza-2-deoxycytidine are currently FDA approved for the treatment of myelodysplastic syndrome. Nonetheless, the mechanism of action behind their clinical efficacy remains unclear. Ongoing clinical trials are attempting to identify tumor suppressor genes that upon re-expression can induce remission and cure in patients. On the other hand, the pleiotropic biological effects of DNMT inhibitors and recent reports demonstrating lack of association between clinical response and methylation reversal of candidate tumor suppressor genes, suggest a complex mechanism behind their clinical efficacy that may involve a cytotoxic effect.
Keywords: 5-azacytidine, decitabine, zebularine, RG108, DNA methylation, DNA methyltransferases
Current Medicinal Chemistry
Title: Development of DNA Methyltransferase Inhibitors for the Treatment of Neoplastic Diseases
Volume: 16 Issue: 17
Author(s): Tamer E. Fandy
Affiliation:
Keywords: 5-azacytidine, decitabine, zebularine, RG108, DNA methylation, DNA methyltransferases
Abstract: Although chemotherapy is considered the mainstay of cancer therapy, unfortunate side effects of chemotherapy create a continuous demand for developing other novel and specific targets for cancer therapy. Re-expression of epigenetically silenced tumor suppressor genes is a rational strategy for the treatment of human neoplasms. Epigenetic modifiers like DNA methyltransferase (DNMT) inhibitors and histone deacteylase (HDAC) inhibitors induce the re-expression of epigenetically silenced genes in vitro and in vivo. Moreover, they demonstrate safety and efficacy against neoplastic diseases in clinical trials. DNMT inhibitors like 5-azacytidine and 5-aza-2-deoxycytidine are currently FDA approved for the treatment of myelodysplastic syndrome. Nonetheless, the mechanism of action behind their clinical efficacy remains unclear. Ongoing clinical trials are attempting to identify tumor suppressor genes that upon re-expression can induce remission and cure in patients. On the other hand, the pleiotropic biological effects of DNMT inhibitors and recent reports demonstrating lack of association between clinical response and methylation reversal of candidate tumor suppressor genes, suggest a complex mechanism behind their clinical efficacy that may involve a cytotoxic effect.
Export Options
About this article
Cite this article as:
Fandy E. Tamer, Development of DNA Methyltransferase Inhibitors for the Treatment of Neoplastic Diseases, Current Medicinal Chemistry 2009; 16 (17) . https://dx.doi.org/10.2174/092986709788612738
DOI https://dx.doi.org/10.2174/092986709788612738 |
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
-
Cytostatic Effect of the Nucleoside Analogue 2-Chloroadenosine on Human Prostate Cancer Cell Line
Current Pharmaceutical Analysis Central Nervous System Depressants and Risk of Hospitalization due to Community-Acquired Pneumonia in very Old Patients
Current Drug Safety Current Understanding of In-stent Restenosis and the Potential Benefit of Drug Eluting Stents
Current Drug Targets - Cardiovascular & Hematological Disorders Mean Platelet Volume: A Link Between Thrombosis and Inflammation?
Current Pharmaceutical Design Angiotensin II-Vasopressin Interactions in The Regulation of Cardiovascular Functions. Evidence for an Impaired Hormonal Sympathetic Reflex in Hypertension and Congestive Heart Failure
Endocrine, Metabolic & Immune Disorders - Drug Targets Multiple Drug Targets in the Management of Type 2 Diabetes
Current Drug Targets Cardiovascular Therapeutics Targets on the NO–sGC–cGMP Signaling Pathway: A Critical Overview
Current Drug Targets Extended-release Formulation Attenuates the Impacts of Fluvastatin on Serum PCSK9 Levels in Humans
Letters in Drug Design & Discovery Potential Role of IL-18 in the Immunopathogenesis of AIDS, HIVAssociated Lipodystrophy and Related Clinical Conditions
Current HIV Research Antibiotic Treatment in Native Valve Infective Endocarditis
Infectious Disorders - Drug Targets Targeting Resveratrol to Mitochondria for Cardiovascular Diseases
Recent Patents on Cardiovascular Drug Discovery A Critical Approach of Guideline Therapeutic Recommendations for NAFLD
Current Vascular Pharmacology Cardiac Imaging in Heart Failure with Comorbidities
Current Cardiology Reviews “Metabolically Healthy” Obesity: Fact or Threat?
Current Diabetes Reviews Recent Patents on Rho Signaling Pathway as Therapeutic Target for Cardiovascular Diseases
Recent Patents on Cardiovascular Drug Discovery Suppression of NF-κB Signaling and P-glycoprotein Function by Gambogic Acid Synergistically Potentiates Adriamycin -induced Apoptosis in Lung Cancer
Current Cancer Drug Targets Bone Marrow Mesenchymal Stem Cells: Agents of Immunomodulation and Neuroprotection
Current Stem Cell Research & Therapy <i>In vitro</i> and <i>In vivo</i> Toxicity Assessment of Metallic Nanoparticulate Systems for Skin Targeting
Current Nanotoxicity and Prevention (Discontinued) New Insights into the Surgical Management of Tetralogy of Fallot: Physiological Fundamentals and Clinical Relevance
Current Pediatric Reviews Ethical and Social Issues in Pharmacogenomics Testing
Current Pharmaceutical Design