Abstract
The targeting of specific DNA repair mechanisms may be a promising strategy to improve the efficacy of antitumor therapy. The cytotoxic effects of the clinically relevant topoisomerase 1 (Top1) poison camptothecins are related to the generation of DNA lesions and tumor cells may be resistant to DNA damaging agents due to increased repair. Tyrosyl- DNA phosphodiesterase 1 (TDP1) is implicated in the repair of strand breaks by removing abortive Top1/DNA complexes. Thus, a role for TDP1 in counteracting DNA damage induced by camptothecins has been proposed. Here, we review the role of TDP1 in DNA repair with particular reference to TDP1 function, its cooperation with other pathways and the development of pharmacological inhibitors.
Keywords: Tyrosyl-DNA phosphodiesterase 1, topoisomerase 1, SCAN-1, camptothecin, DNA repair pathways, drug resistance
Current Medicinal Chemistry
Title: Tyrosyl-DNA Phosphodiesterase 1 Targeting for Modulation of Camptothecin-Based Treatment
Volume: 17 Issue: 15
Author(s): G. L. Beretta, G. Cossa, L. Gatti, F. Zunino and P. Perego
Affiliation:
Keywords: Tyrosyl-DNA phosphodiesterase 1, topoisomerase 1, SCAN-1, camptothecin, DNA repair pathways, drug resistance
Abstract: The targeting of specific DNA repair mechanisms may be a promising strategy to improve the efficacy of antitumor therapy. The cytotoxic effects of the clinically relevant topoisomerase 1 (Top1) poison camptothecins are related to the generation of DNA lesions and tumor cells may be resistant to DNA damaging agents due to increased repair. Tyrosyl- DNA phosphodiesterase 1 (TDP1) is implicated in the repair of strand breaks by removing abortive Top1/DNA complexes. Thus, a role for TDP1 in counteracting DNA damage induced by camptothecins has been proposed. Here, we review the role of TDP1 in DNA repair with particular reference to TDP1 function, its cooperation with other pathways and the development of pharmacological inhibitors.
Export Options
About this article
Cite this article as:
Beretta L. G., Cossa G., Gatti L., Zunino F. and Perego P., Tyrosyl-DNA Phosphodiesterase 1 Targeting for Modulation of Camptothecin-Based Treatment, Current Medicinal Chemistry 2010; 17 (15) . https://dx.doi.org/10.2174/092986710790979971
DOI https://dx.doi.org/10.2174/092986710790979971 |
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
Clinical and Computational Analysis of Variants Associated with Rare Genetic Disorders
This thematic issue focuses on integrating clinical insights and computational techniques in the study of genetic variants linked to rare genetic disorders. Rare diseases, while individually uncommon, collectively affect millions of people worldwide, making their understanding and diagnosis critical to personalized medicine. Advances in next-generation sequencing (NGS) and bioinformatics tools ...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
-
LFA-1 on Leukemic Cells as a Target for Therapy or Drug Delivery
Current Pharmaceutical Design <i>In vivo</i> PET Imaging of EGFR Expression: An Overview of Radiolabeled EGFR TKIs
Current Topics in Medicinal Chemistry Strategies to Increase the Oral Bioavailability of Nucleoside Analogs
Current Medicinal Chemistry STAT3 Regulation of Glioblastoma Pathogenesis
Current Molecular Medicine Protective Effects of Curcumin against Iron-induced Toxicity
Current Pharmaceutical Biotechnology Sugar Based Biopolymers in Nanomedicine; New Emerging Era for Cancer Imaging and Therapy
Current Topics in Medicinal Chemistry Melatonin: Pharmacology, Functions and Therapeutic Benefits
Current Neuropharmacology Prolonged Air Leak After Lung Resection
Current Respiratory Medicine Reviews The Applications of Next-generation Sequencing (NGS) in Drug Development for Cancer Therapy
Current Analytical Chemistry The Role of Oxidative Stress Modulators in Breast Cancer
Current Medicinal Chemistry Nontoxic-dose of Deguelin Induce NPMc+ AML Cell Differentiation by Selectively Targeting Mt NPM1/SIRT1 Instead of HDAC1/3
Current Cancer Drug Targets Radix Stephaniae Tetrandrine: An Emerging Role for Management of Breast Cancer
Current Pharmaceutical Design Prognostic and Predictive Biomarkers in Colorectal Cancer. From the Preclinical Setting to Clinical Practice
Current Cancer Drug Targets Evaluation of Estrogen Receptor α and ß Genes Expression in Normal and Neoplastic Mammary Gland in Dogs by Real-time PCR
Current Pharmacogenomics and Personalized Medicine Nanoemulsions for Improved Efficacy of Phytotherapeutics- A Patent Perspective
Recent Patents on Nanotechnology Cyclin D1 Gene Silencing by siRNA in Ex Vivo Human Tissue Cultures
Current Drug Delivery Chemogenomics of Sensitivity and Resistance to Anticancer Drugs
Current Pharmacogenomics Nanoparticles in Combating Cancer: Opportunities and Limitations: A Brief Review
Current Medicinal Chemistry Phosphonomethoxyalkyl Analogs of Nucleotides
Current Pharmaceutical Design Development of PET Probes for Cancer Imaging
Current Topics in Medicinal Chemistry