Abstract
Methylation of CpG islands in many tumor suppressor genes with or without changes in histone acetylation is an important mechanism of gene silencing during the development of different types of cancer. There are at least two types of CpG island methylator phenotypes in intestinal- and diffuse -types of gastric cancer. Hypermethylation of the p16 and of hMLH1 promoters is preferentially found in intestinal-type gastric carcinoma, while concordant hypermethylation of the CDH1 and RAR-β2 promoters is predominantly associated with diffuse-type gastric carcinoma. Loss of RUNX3 and pS2 expression by promoter methylation is a common event in both types of gastric carcinoma. These results suggest that CpG island methylator phenotype may be one of the major pathways responsible for the development of the two types of gastric cancer and that RUNX3 and RAR-β2 may provide potential targets for therapeutic intervention to treat gastric cancer. Reactivation of RUNX3 and RAR-β2 by demethylating agents [e.g., 5-aza-2-deoxycytidine (DAC)] and histone deacetylase (HDAC) inhibitors [e.g., suberoylanilide hydroxamic acid (SAHA)] may be clinical useful for gastric cancer therapy with retinoids. This article will provide an overview of the molecular machinery that underlies two types of gastric cancer and focus on HDAC inhibitors that are potentially effective anticancer agents, not only for breast and prostate cancers but also for gastric cancer.
Keywords: runx, gastric cancer, dna methylation, histone acetylation, hdac inhibitor
Current Cancer Therapy Reviews
Title: RUNX3 and Retinoic Acid Receptor β DNA Methylation as Novel Targets for Gastric Cancer Therapy
Volume: 1 Issue: 2
Author(s): Eiichi Tahara and Reuben Lotan
Affiliation:
Keywords: runx, gastric cancer, dna methylation, histone acetylation, hdac inhibitor
Abstract: Methylation of CpG islands in many tumor suppressor genes with or without changes in histone acetylation is an important mechanism of gene silencing during the development of different types of cancer. There are at least two types of CpG island methylator phenotypes in intestinal- and diffuse -types of gastric cancer. Hypermethylation of the p16 and of hMLH1 promoters is preferentially found in intestinal-type gastric carcinoma, while concordant hypermethylation of the CDH1 and RAR-β2 promoters is predominantly associated with diffuse-type gastric carcinoma. Loss of RUNX3 and pS2 expression by promoter methylation is a common event in both types of gastric carcinoma. These results suggest that CpG island methylator phenotype may be one of the major pathways responsible for the development of the two types of gastric cancer and that RUNX3 and RAR-β2 may provide potential targets for therapeutic intervention to treat gastric cancer. Reactivation of RUNX3 and RAR-β2 by demethylating agents [e.g., 5-aza-2-deoxycytidine (DAC)] and histone deacetylase (HDAC) inhibitors [e.g., suberoylanilide hydroxamic acid (SAHA)] may be clinical useful for gastric cancer therapy with retinoids. This article will provide an overview of the molecular machinery that underlies two types of gastric cancer and focus on HDAC inhibitors that are potentially effective anticancer agents, not only for breast and prostate cancers but also for gastric cancer.
Export Options
About this article
Cite this article as:
Tahara Eiichi and Lotan Reuben, RUNX3 and Retinoic Acid Receptor β DNA Methylation as Novel Targets for Gastric Cancer Therapy, Current Cancer Therapy Reviews 2005; 1 (2) . https://dx.doi.org/10.2174/1573394054021781
DOI https://dx.doi.org/10.2174/1573394054021781 |
Print ISSN 1573-3947 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6301 |
Call for Papers in Thematic Issues
Current progress in Protein Degradation and Cancer Therapy
argeted Protein Degradation is gaining momentum in cancer therapy, it facilitate targeting undruggable proteins, it overcome cancer resistance and avoid undesirable side effects. Thus small molecules degraders have emerged as novel therapeutic strategy. Targeted protein degradation (TPD), the process of eliminating a protein of interest hold a great promise for ...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
-
Current Immune Therapies of Autoimmune Disease of the Nervous System with Special Emphasis to Multiple Sclerosis
Current Pharmaceutical Design High-density Lipoprotein, Vascular Risk, Cancer and Infection: A Case of Quantity and Quality?
Current Medicinal Chemistry Combining Oncolytic Virotherapy and Cytotoxic Therapies to Fight Cancer
Current Pharmaceutical Design Maternal Sepsis 2010: Early Recognition and Aggressive Treatment with Early Goal Directed Therapy can Improve Maternal Outcomes
Current Women`s Health Reviews Tubulin-Targeting Agents in Hybrid Drugs
Current Medicinal Chemistry Anaemia in Diabetes: An Emerging Complication of Microvascular Disease
Current Diabetes Reviews The Role of COX-2 in Acute Pain and the Use of Selective COX-2 Inhibitors for Acute Pain Relief
Current Pharmaceutical Design Prodrugs for Targeted Tumor Therapies: Recent Developments in ADEPT, GDEPT and PMT
Current Pharmaceutical Design CCR5 as a Potential Target in Cancer Therapy: Inhibition or Stimulation?
Anti-Cancer Agents in Medicinal Chemistry Ursolic and Oleanolic Acids as Potential Anticancer Agents Acting in the Gastrointestinal Tract
Mini-Reviews in Organic Chemistry TGF-Beta Type I Receptor (Alk5) Kinase Inhibitors in Oncology
Current Pharmaceutical Biotechnology HspB1 Dynamic Phospho-Oligomeric Structure Dependent Interactome as Cancer Therapeutic Target
Current Molecular Medicine Restoration of Antitumor Immunity Through Selective Inhibition of Myeloid Derived Suppressor Cells by Anticancer Therapies
Current Molecular Medicine Preparation and Surface Modification of Polymeric Nanoparticles for Drug Delivery: State of the Art
Recent Patents on Drug Delivery & Formulation Chronic Inflammation in the Pancreas and Salivary Glands - Lessons from Similarities and Differences in Pathophysiology and Treatment Modalities
Current Pharmaceutical Design Coumarins as Potential Anti-drug Resistant Cancer Agents: A Mini Review
Current Topics in Medicinal Chemistry The Design of Amphiphilic Polymeric Micelles of Curcumin for Cancer Management
Current Medicinal Chemistry Application of Nanoparticles in Oral Delivery of Immediate Release Formulations
Current Nanoscience Therapeutic Use of MicroRNAs in Cancer
Anti-Cancer Agents in Medicinal Chemistry The Inhibitor of Growth (ING) Gene Family: Potential Role in Cancer Therapy
Current Cancer Drug Targets