Abstract
Tumor resistance to cytotoxic chemotherapy drugs and their toxicity to normal cells are major clinical obstacles to anticancer therapy effectiveness. Alterations in various DNA repair pathways play a key role in the development of both mechanisms of drug resistance and toxicity. Since deregulation of the DNA damage response and alterations in DNA repair pathways are relatively common in human cancer, the knowledge of these alterations in cancer cells would be an important predictive factor for the clinical response to chemotherapy and a useful guide in designing an appropriate therapeutic strategy. This review is focused on the mismatch repair (MMR) pathway and the O6-methylguanine-DNA-methyltransferase (MGMT) repair protein. In particular, we examine how inactivation of these DNA repair mechanisms might affect the response of tumor cells to chemotherapy, with a special emphasis on agents inducing methylation and oxidative DNA damage and interstrand DNA cross-links (ICLs). In addition, we provide novel experimental evidence indicating that MMR is required for efficient repair of ICLs via stabilization of RAD51 containing repair intermediates. Finally, we discuss possible emerging therapeutical strategies for treating MMR-defective tumors.
Anti-Cancer Agents in Medicinal Chemistry
Title: Role of Mismatch Repair and MGMT in Response to Anticancer Therapies
Volume: 8 Issue: 4
Author(s): Ida Casorelli, Maria Teresa Russo and Margherita Bignami
Affiliation:
Abstract: Tumor resistance to cytotoxic chemotherapy drugs and their toxicity to normal cells are major clinical obstacles to anticancer therapy effectiveness. Alterations in various DNA repair pathways play a key role in the development of both mechanisms of drug resistance and toxicity. Since deregulation of the DNA damage response and alterations in DNA repair pathways are relatively common in human cancer, the knowledge of these alterations in cancer cells would be an important predictive factor for the clinical response to chemotherapy and a useful guide in designing an appropriate therapeutic strategy. This review is focused on the mismatch repair (MMR) pathway and the O6-methylguanine-DNA-methyltransferase (MGMT) repair protein. In particular, we examine how inactivation of these DNA repair mechanisms might affect the response of tumor cells to chemotherapy, with a special emphasis on agents inducing methylation and oxidative DNA damage and interstrand DNA cross-links (ICLs). In addition, we provide novel experimental evidence indicating that MMR is required for efficient repair of ICLs via stabilization of RAD51 containing repair intermediates. Finally, we discuss possible emerging therapeutical strategies for treating MMR-defective tumors.
Export Options
About this article
Cite this article as:
Casorelli Ida, Russo Teresa Maria and Bignami Margherita, Role of Mismatch Repair and MGMT in Response to Anticancer Therapies, Anti-Cancer Agents in Medicinal Chemistry 2008; 8 (4) . https://dx.doi.org/10.2174/187152008784220276
DOI https://dx.doi.org/10.2174/187152008784220276 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
- 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
-
Patient-derived Tumor Models for Diffuse Intrinsic Pontine Gliomas
Current Neuropharmacology Cell-penetrating Peptides for Cancer-targeting Therapy and Imaging
Current Cancer Drug Targets Recent Trends in Targeted Anticancer Prodrug and Conjugate Design
Current Medicinal Chemistry Targeting the Expression of Anti-Apoptotic Proteins by Antisense Oligonucleotides
Current Drug Targets Neuropeptides as Autocrine Growth Factors in Cancer Cells
Current Pharmaceutical Design Targeting Epigenetics in Nervous System Disease
CNS & Neurological Disorders - Drug Targets Stem Cell Patents: An Innovative Approach to Anti-Cancer Drug Discovery
Recent Patents on Anti-Cancer Drug Discovery Targeting Blood Vessels for the Treatment of Non-Small Cell Lung Cancer
Current Cancer Drug Targets Signal Transduction Therapy Targeting Apoptosis Pathways in Cancers
Current Signal Transduction Therapy Possible Binding Mode Analysis of Pyrazolo-triazole Hybrids as Potential Anticancer Agents through Validated Molecular Docking and 3D-QSAR Modeling Approaches
Letters in Drug Design & Discovery MicroRNA Mediated Network and DNA Methylation in Colorectal Cancer
Protein & Peptide Letters Pharmacological Inhibition of Poly(ADP-ribose) Polymerase (PARP) Activity in PARP-1 Silenced Tumour Cells Increases Chemosensitivity to Temozolomide and to a N3-Adenine Selective Methylating Agent
Current Cancer Drug Targets Chemistry of Tumour Targeted T1 Based MRI Contrast Agents
Current Topics in Medicinal Chemistry Radiopharmaceutical Chemistry with Iodine-124: A Non-Standard Radiohalogen for Positron Emission Tomography
Medicinal Chemistry Viral Vectors for Gene-Directed Enzyme Prodrug Therapy
Current Gene Therapy Membrane Interacting Peptides: A Review
Current Protein & Peptide Science The Protein-Protein Interaction-Mediated Inactivation of PTEN
Current Molecular Medicine Biocompatible Targeting Hydrogels for Breast Cancer Treatment
Mini-Reviews in Medicinal Chemistry Cell Bystander Effect Induced by Radiofrequency Electromagnetic Fields and Magnetic Nanoparticles
Current Nanoscience Role of Monocarboxylate Transporters in Drug Delivery to the Brain
Current Pharmaceutical Design