Abstract
Genotoxic anticancer drugs explicate their effects damaging DNA, thus triggering a coordinated signal-transduction network called DNA Damage Response (DDR). Ataxia Telangiectasia Mutated (ATM) protein plays a central role in this response: activated by DNA damage, ATM phosphorylates itself and downstream effectors that arrest cell cycle allowing for DNA repair or, should DNA damage be too severe and not retrievable, inducing apoptosis. ATM is a worth-investigating target for tumor radio- and chemosensitization. During last years, pharmaceutical industries and research laboratories have developed a series of small molecules, capable to inhibit ATM with increasing specificity. Several preclinical studies have demonstrated that these inhibitors alone or in association with other treatments may improve therapeutic outcomes. In this review we discuss ATM inhibitors so far developed, focussing on recent acquisitions on their potential antineoplastic usefulness.
Keywords: ATM, chemotherapy, glioma, inhibitor, radiotherapy, resistance, sensitization.
Current Drug Targets
Title:Targeting the Ataxia Telangiectasia Mutated Protein in Cancer Therapy
Volume: 17 Issue: 2
Author(s): Donatella Vecchio and Guido Frosina
Affiliation:
Keywords: ATM, chemotherapy, glioma, inhibitor, radiotherapy, resistance, sensitization.
Abstract: Genotoxic anticancer drugs explicate their effects damaging DNA, thus triggering a coordinated signal-transduction network called DNA Damage Response (DDR). Ataxia Telangiectasia Mutated (ATM) protein plays a central role in this response: activated by DNA damage, ATM phosphorylates itself and downstream effectors that arrest cell cycle allowing for DNA repair or, should DNA damage be too severe and not retrievable, inducing apoptosis. ATM is a worth-investigating target for tumor radio- and chemosensitization. During last years, pharmaceutical industries and research laboratories have developed a series of small molecules, capable to inhibit ATM with increasing specificity. Several preclinical studies have demonstrated that these inhibitors alone or in association with other treatments may improve therapeutic outcomes. In this review we discuss ATM inhibitors so far developed, focussing on recent acquisitions on their potential antineoplastic usefulness.
Export Options
About this article
Cite this article as:
Vecchio Donatella and Frosina Guido, Targeting the Ataxia Telangiectasia Mutated Protein in Cancer Therapy, Current Drug Targets 2016; 17 (2) . https://dx.doi.org/10.2174/1389450115666141110154621
DOI https://dx.doi.org/10.2174/1389450115666141110154621 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...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
-
Generation of Human Single-chain Antibody to the CD99 Cell Surface Determinant Specifically Recognizing Ewing’s Sarcoma Tumor Cells
Current Pharmaceutical Biotechnology The BET-Bromodomain Inhibitor JQ1 Reduces Inflammation and Tau Phosphorylation at Ser396 in the Brain of the 3xTg Model of Alzheimer’s Disease
Current Alzheimer Research Biomolecules Linked to Transition Metal Complexes - New Chances for Chemotherapy
Current Medicinal Chemistry Stat3 Orchestrates Tumor Development and Progression: The Achilles Heel of Head and Neck Cancers?
Current Cancer Drug Targets Improvement of Tumor Localization of Photosensitizers for Photodynamic Therapy and Its Application for Tumor Diagnosis
Current Topics in Medicinal Chemistry Editorial: Drug Targets and Biomarkers for Obstetric/Gynecologic/Reproductive Diseases
Current Drug Targets Silver Nanoparticles: Synthesis, Characterization and their Application as a Sustainable Catalyst for Organic Transformations
Current Organic Chemistry Sequential Bilateral Internal Jugular Vein Thrombosis: A Case Report and Review of this Rare Medical Entity
Vascular Disease Prevention (Discontinued) MR Imaging Findings of Uterine Cervical Carcinoma
Current Medical Imaging Flow Shear Induced Changes in Membrane Fluidity: Dependence on Cell- Substrate Adhesion Strength
Current Analytical Chemistry The Role of Connexins in Carcinogenesis: Review of Current Knowledge
Current Signal Transduction Therapy Critical Roles of EGFR Family Members in Breast Cancer and Breast Cancer Stem Cells: Targets for Therapy
Current Pharmaceutical Design Cytokines and Hormones in the Regulation of Hypoxia Inducible Factor-1α (HIF-1α)
Cardiovascular & Hematological Agents in Medicinal Chemistry CEST MRI for Molecular Imaging of Brain Metabolites
Current Molecular Imaging (Discontinued) Targeting Cancer with Epi-Drugs: A Precision Medicine Perspective
Current Pharmaceutical Biotechnology Co-formulation of P-glycoprotein Substrate and Inhibitor in Nanocarriers: An Emerging Strategy for Cancer Chemotherapy
Current Cancer Drug Targets HLA Associations with Nasopharyngeal Carcinoma
Current Molecular Medicine MicroRNA-34 Family, Mechanisms of Action in Cancer: A Review
Current Cancer Drug Targets Base Excision Repair: Contribution to Tumorigenesis and Target in Anticancer Treatment Paradigms
Current Medicinal Chemistry A Review on Medical Image Registration as an Optimization Problem
Current Medical Imaging