Abstract
DNA interstrand crosslinkers, a chemically diverse group of compounds which also induce alkylation of bases and DNA intrastrand crosslinks, are extensively utilized for cancer therapy. Understanding the cellular response to DNA damage induced by these agents is critical for more effective utilization of these compounds and for the identification of novel therapeutic targets. Importantly, the repair of DNA interstrand crosslinks (ICLs) involves many distinct DNA repair pathways, including nucleotide excision repair, translesion synthesis (TLS), and homologous recombination (HR). Additionally, proteins implicated in the pathophysiology of the multigenic disease Fanconi anemia (FA) have a role in the repair of ICLs that is not well understood. Cells from FA patients are hypersensitive to agents that induce ICLs, therefore FA proteins are potentially novel therapeutic targets. Here we will review current research directed at identifying FA genes and understanding the function of FA proteins in DNA damage responses. We will also examine interactions of FA proteins with other repair proteins and pathways, including signaling networks, which are potentially involved in ICL repair. Potential approaches to the modulation of FA protein function to enhance therapeutic outcome will be discussed. Also, mutation of many genes that encode proteins involved in ICL repair, including FA genes, increases susceptibility to cancer. A better understanding of these pathways is therefore critical for the design of individualized therapies tailored to the genetic profile of a particular malignancy. For this purpose, we will also review evidence for the association of mutation of FA genes with cancer in non-FA patients.
Keywords: Fanconi anemia, DNA interstrand crosslinks, homologous recombination, DNA repair, DNA damage responses, chemotherapy, bifunctional alkylating agents, platinum compounds
Current Cancer Drug Targets
Title: Fanconi Anemia Proteins, DNA Interstrand Crosslink Repair Pathways, and Cancer Therapy
Volume: 9 Issue: 1
Author(s): Paul R. Andreassen and Keqin Ren
Affiliation:
Keywords: Fanconi anemia, DNA interstrand crosslinks, homologous recombination, DNA repair, DNA damage responses, chemotherapy, bifunctional alkylating agents, platinum compounds
Abstract: DNA interstrand crosslinkers, a chemically diverse group of compounds which also induce alkylation of bases and DNA intrastrand crosslinks, are extensively utilized for cancer therapy. Understanding the cellular response to DNA damage induced by these agents is critical for more effective utilization of these compounds and for the identification of novel therapeutic targets. Importantly, the repair of DNA interstrand crosslinks (ICLs) involves many distinct DNA repair pathways, including nucleotide excision repair, translesion synthesis (TLS), and homologous recombination (HR). Additionally, proteins implicated in the pathophysiology of the multigenic disease Fanconi anemia (FA) have a role in the repair of ICLs that is not well understood. Cells from FA patients are hypersensitive to agents that induce ICLs, therefore FA proteins are potentially novel therapeutic targets. Here we will review current research directed at identifying FA genes and understanding the function of FA proteins in DNA damage responses. We will also examine interactions of FA proteins with other repair proteins and pathways, including signaling networks, which are potentially involved in ICL repair. Potential approaches to the modulation of FA protein function to enhance therapeutic outcome will be discussed. Also, mutation of many genes that encode proteins involved in ICL repair, including FA genes, increases susceptibility to cancer. A better understanding of these pathways is therefore critical for the design of individualized therapies tailored to the genetic profile of a particular malignancy. For this purpose, we will also review evidence for the association of mutation of FA genes with cancer in non-FA patients.
Export Options
About this article
Cite this article as:
Andreassen R. Paul and Ren Keqin, Fanconi Anemia Proteins, DNA Interstrand Crosslink Repair Pathways, and Cancer Therapy, Current Cancer Drug Targets 2009; 9 (1) . https://dx.doi.org/10.2174/156800909787314011
DOI https://dx.doi.org/10.2174/156800909787314011 |
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
-
Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer
Current Medicinal Chemistry Concomitant CXCR4 and CXCR7 Expression Predicts Poor Prognosis in Renal Cancer
Current Cancer Drug Targets The ERK 1 and 2 Pathway in the Nervous System: From Basic Aspects to Possible Clinical Applications in Pain and Visceral Dysfunction
Current Neuropharmacology Drug Resistance: Challenges to Effective Therapy
Current Cancer Drug Targets Fibroblast Growth Factor Receptor Signaling in Cancer Biology and Treatment
Current Signal Transduction Therapy Epigenetic Regulation of Genes Encoding Drug-Metabolizing Enzymes and Transporters; DNA Methylation and Other Mechanisms
Current Drug Metabolism miR-126 as a Therapeutic Agent for Diabetes Mellitus
Current Pharmaceutical Design A Combined Approach with Rituximab Plus Anti-TRAIL-R Agonistic Antibodies for the Treatment of Haematological Malignancies
Current Pharmaceutical Design Thiosemicarbazones as Potent Anticancer Agents and their Modes of Action
Mini-Reviews in Medicinal Chemistry PET Designated Flouride-18 Production and Chemistry
Current Topics in Medicinal Chemistry Current Concepts in Reprogramming Somatic Cells to Pluripotent State
Current Stem Cell Research & Therapy ETS Proteins and MMPs: Partners in Invasion and Metastasis
Medicinal Chemistry Reviews - Online (Discontinued) An Overview of Phytotherapeutic Approaches for the Treatment of Benign Prostatic Hyperplasia
Mini-Reviews in Medicinal Chemistry Fluorine-18 Labeled Amino Acids for Oncologic Imaging with Positron Emission Tomography
Current Topics in Medicinal Chemistry Patent Selections:
Recent Patents on Anti-Cancer Drug Discovery A Review on Theragnostic Applications of Micrornas and Long Non- Coding RNAs in Colorectal Cancer
Current Topics in Medicinal Chemistry Simultaneous Amplification of HER-2 (ERBB2) and Topoisomerase IIα (TOP2A) Genes - Molecular Basis for Combination Chemotherapy in Cancer
Current Cancer Drug Targets Oral Precancerous Lesions Show Increased Levels of Glutathione Compared to Cancerous Tissue
Current Nutrition & Food Science Notch Signalling Pathways and Their Importance in the Treatment of Cancers
Current Drug Targets Jab1-siRNA Induces Cell Growth Inhibition and Cell Cycle Arrest in Gall Bladder Cancer Cells via Targeting Jab1 Signalosome
Anti-Cancer Agents in Medicinal Chemistry