![conference banner](/images/conference-banner.jpeg)
Abstract
Background: Defects in DNA repair pathways are causal factors for a plethora of solid tumours, but are only just beginning to be explored in haematological malignancies. Genomic instability, including mutations in DNA sequences, chromosomal aneuploidy, translocations and gene amplifications contribute to the development and progression of AML. Prior DNA damaging agent exposure enhances the risk of developing AML, as does inheritance of genetic syndromes that involve alterations in DNA repair pathways. Furthermore, these same variations are associated with sensitivity and resistance to a range of chemotherapeutics. Taken together, these studies suggest that defects within DNA repair pathways are involved in the pathogenesis and prognosis of AML.
Objective: This review summarises the major DNA repair pathways, and presents an overview of current data on DNA damage repair abnormalities in AML as they pertain to the development of resistance and sensitivity to chemotherapeutics in AML. Additionally, the use of drugs that modulate these pathways as new treatments for AML will be explored herein.
Conclusion: This review highlights that abnormalities in DNA repair mechanisms in AML cells are potential novel treatment targets for AML patients with disease that is resistant to current therapies.
Keywords: Acute myeloid leukaemia, base excision repair, chemosensitivity, direct enzymatic repair, DNA repair, homologous recombination, nucleotide excision repair, non-homologous end joining.
Current Drug Targets
Title:The Role of DNA Repair Pathways in AML Chemosensitivity
Volume: 19 Issue: 10
Author(s): Elizabeth A. Pearsall, Lisa F. Lincz and Kathryn A. Skelding*
Affiliation:
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle, Callaghan, New South Wales,Australia
Keywords: Acute myeloid leukaemia, base excision repair, chemosensitivity, direct enzymatic repair, DNA repair, homologous recombination, nucleotide excision repair, non-homologous end joining.
Abstract: Background: Defects in DNA repair pathways are causal factors for a plethora of solid tumours, but are only just beginning to be explored in haematological malignancies. Genomic instability, including mutations in DNA sequences, chromosomal aneuploidy, translocations and gene amplifications contribute to the development and progression of AML. Prior DNA damaging agent exposure enhances the risk of developing AML, as does inheritance of genetic syndromes that involve alterations in DNA repair pathways. Furthermore, these same variations are associated with sensitivity and resistance to a range of chemotherapeutics. Taken together, these studies suggest that defects within DNA repair pathways are involved in the pathogenesis and prognosis of AML.
Objective: This review summarises the major DNA repair pathways, and presents an overview of current data on DNA damage repair abnormalities in AML as they pertain to the development of resistance and sensitivity to chemotherapeutics in AML. Additionally, the use of drugs that modulate these pathways as new treatments for AML will be explored herein.
Conclusion: This review highlights that abnormalities in DNA repair mechanisms in AML cells are potential novel treatment targets for AML patients with disease that is resistant to current therapies.
Export Options
About this article
Cite this article as:
Pearsall A. Elizabeth, Lincz F. Lisa and Skelding A. Kathryn *, The Role of DNA Repair Pathways in AML Chemosensitivity, Current Drug Targets 2018; 19 (10) . https://dx.doi.org/10.2174/1389450119666180110093713
DOI https://dx.doi.org/10.2174/1389450119666180110093713 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
Drug-Targeted Approach with Polymer Nanocomposites for Improved Therapeutics
Polymer nanocomposites have been recognized as an advanced and cutting-edge technique in drug targeting administration. These materials combine the unique features of nanoparticles with the adaptability of polymers to produce highly personalized drug administration devices. Integrating nanoparticles containing pharmaceuticals into a polymer matrix enables researchers to regulate the rates at ...read more
RNA Molecules in the Treatment of Human Diseases
Messenger and non-coding RNAs, including long and small transcripts, are mediators of gene expression. Gene expression at the RNA level shows significant aberrations in human diseases, including cancer, leukemia, lymphoma, cardiovascular diseases, and neurological disorders. Human transcripts serve either as biomarkers of diagnosis, prognosis, prediction of treatment response, and/or therapy ...read more
![Wayfinder Image](/images/wayfinder.jpg)
- 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
-
Wnt/beta-Catenin Signaling and Small Molecule Inhibitors
Current Pharmaceutical Design Parallel Gene Expression Profiling of Mantle Cell Lymphoma – How Do We Transform ´Omics Data into Clinical Practice
Current Genomics BCR-ABL Inhibitors in Chronic Myeloid Leukemia: Process Chemistry and Biochemical Profile
Current Medicinal Chemistry Caffeic Acid Phenethyl Ester Effects: In Silico Study of its Osteoimmunological Mechanisms
Letters in Drug Design & Discovery (Review Article) Screening for Disease-Markers and Investigating Drug Effects by Proteome Profiling: Can it Meet Expectations?
Combinatorial Chemistry & High Throughput Screening Advancement and Strategies for the Development of Peptide-drug Conjugates: Pharmacokinetic Modulation, Role and Clinical Evidence against Cancer Management
Current Cancer Drug Targets The Emerging Role of LncRNA FENDRR in Multiple Cancers: A Review
Current Molecular Medicine CAR T-cell Therapy: A New Era in Cancer Immunotherapy
Current Pharmaceutical Biotechnology Influence of Aldo-keto Reductase 1C3 in Prostate Cancer - A Mini Review
Current Cancer Drug Targets Patent Selections:
Recent Patents on Anti-Cancer Drug Discovery Clinical Pharmacology of Cyclophosphamide and Ifosfamide
Current Drug Therapy The Significance of Transferrin Receptors in Oncology: the Development of Functional Nano-based Drug Delivery Systems
Current Drug Delivery Bioplex Technology: Novel Synthetic Gene Delivery Pharmaceutical Based on Peptides Anchored to Nucleic Acids
Current Pharmaceutical Design Recombinant Human Serum Albumin Fusion Proteins and Novel Applications in Drug Delivery and Therapy
Current Pharmaceutical Design Endoradiotherapy with Peptides - Status and Future Development
Current Medicinal Chemistry Platelet Ca2+ATPases: Identification and Regulation in Hypertension
Current Hypertension Reviews HSP60 as a Drug Target
Current Pharmaceutical Design Retroviral Protein Transfer: Falling Apart to Make an Impact
Current Gene Therapy Exploring Proteomic Drug Targets, Therapeutic Strategies and Protein - Protein Interactions in Cancer: Mechanistic View
Current Cancer Drug Targets Thermodynamics and Electro-Biologic Prospects for Therapies to Intervene in Cancer Progression
Current Cancer Therapy Reviews