Abstract
The main aim of current cancer research is to find a way to selectively affect the tumor cells, while leaving normal cells intact. Ataxia telangiectasia and Rad3-related kinase (ATR), a member of the phosphatidylinositol-3-related protein kinases (PIKK), represents a candidate target for achieving this goal. ATR kinase is one of the main kinases of the DNA damage response signaling pathway and responds to DNA damage caused by replication stress and various genotoxic agents (i.e. chemotherapy, ionizing radiation, ultraviolet light). ATR activation triggers cell cycle checkpoints, DNA repair and apoptosis, but also resistance of tumor cells to DNA damaging agents, through stress support under replication stress. Thus, the inhibition of ATR leads to increased effectiveness of cancer therapy and in addition enables highly selective targeting of cancer cells through synthetic lethal interactions. Despite this great potential, only a few potent and selective inhibitors of ATR kinase have been developed to date. However, those which have been developed provide great promise, and are under evaluation in many current preclinical and clinical trials. The purpose of this review is to summarize the potential of ATR inhibitors and the medicinal chemistry efforts which resulted in their identification.
Keywords: Ataxia telangiectasia and Rad3-related kinase (ATR), cancer, chemosensitization, DNA damage response, phosphatidylinositol 3-kinase-related protein kinases (PIKK), radiosensitization, synthetic lethality.
Current Cancer Drug Targets
Title:Small Molecules Targeting Ataxia Telangiectasia and Rad3-Related (ATR) Kinase: An Emerging way to Enhance Existing Cancer Therapy
Volume: 16 Issue: 3
Author(s): Martin Andrs, Jan Korabecny, Eugenie Nepovimova, Daniel Jun, Zdenek Hodny and Kamil Kuca
Affiliation:
Keywords: Ataxia telangiectasia and Rad3-related kinase (ATR), cancer, chemosensitization, DNA damage response, phosphatidylinositol 3-kinase-related protein kinases (PIKK), radiosensitization, synthetic lethality.
Abstract: The main aim of current cancer research is to find a way to selectively affect the tumor cells, while leaving normal cells intact. Ataxia telangiectasia and Rad3-related kinase (ATR), a member of the phosphatidylinositol-3-related protein kinases (PIKK), represents a candidate target for achieving this goal. ATR kinase is one of the main kinases of the DNA damage response signaling pathway and responds to DNA damage caused by replication stress and various genotoxic agents (i.e. chemotherapy, ionizing radiation, ultraviolet light). ATR activation triggers cell cycle checkpoints, DNA repair and apoptosis, but also resistance of tumor cells to DNA damaging agents, through stress support under replication stress. Thus, the inhibition of ATR leads to increased effectiveness of cancer therapy and in addition enables highly selective targeting of cancer cells through synthetic lethal interactions. Despite this great potential, only a few potent and selective inhibitors of ATR kinase have been developed to date. However, those which have been developed provide great promise, and are under evaluation in many current preclinical and clinical trials. The purpose of this review is to summarize the potential of ATR inhibitors and the medicinal chemistry efforts which resulted in their identification.
Export Options
About this article
Cite this article as:
Andrs Martin, Korabecny Jan, Nepovimova Eugenie, Jun Daniel, Hodny Zdenek and Kuca Kamil, Small Molecules Targeting Ataxia Telangiectasia and Rad3-Related (ATR) Kinase: An Emerging way to Enhance Existing Cancer Therapy, Current Cancer Drug Targets 2016; 16 (3) . https://dx.doi.org/10.2174/156800961603160206122927
DOI https://dx.doi.org/10.2174/156800961603160206122927 |
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
-
Aging and Inflammation: Etiological Culprits of Cancer
Current Aging Science Propofol Protects Against TNF-α-induced Blood-brain Barrier Disruption via the PIM-1/eNOS/NO Pathway
Current Neurovascular Research Runx1/AML1 is a Guardian of Hematopoietic Stem Cells
Current Cancer Therapy Reviews Cholangiocarcinoma Therapeutics: An Update
Current Cancer Drug Targets Anti-Gene Strategies to Down-Regulate Gene Expression in Mammalian Cells
Current Pharmaceutical Design microRNAs in Cancer: Lessons from Melanoma
Current Pharmaceutical Design Imatinib Mesylate (Gleevec©): Targeted Therapy Against Cancer with Immune Properties
Endocrine, Metabolic & Immune Disorders - Drug Targets Molecular Imaging of Apoptosis with Radio-Labeled Annexin A5 Focused on the Evaluation of Tumor Response to Chemotherapy
Anti-Cancer Agents in Medicinal Chemistry Nuclear Export as a Novel Therapeutic Target: The CRM1 Connection
Current Cancer Drug Targets Baicalin-induced Cytotoxicity and Apoptosis in Multidrug-resistant MC3/5FU Mucoepidermoid Carcinoma Cell Line
Letters in Drug Design & Discovery Sumoylation in Cellular Senescence and Aging
Current Molecular Medicine MicroRNA in Multiple Myeloma - A Role in Pathogenesis and Prognostic Significance
Current Medicinal Chemistry Specific Targeting of HER2-Positive Head and Neck Squamous Cell Carcinoma Line HN5 by Idarubicin-ZHER2 Affibody Conjugate
Current Cancer Drug Targets The Anticancer Face of Interferon Alpha (IFN-Alpha): From Biology to Clinical Results, with a Focus on Melanoma
Current Medicinal Chemistry Natural Products Targeting Autophagy via the PI3K/Akt/mTOR Pathway as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Ferroptosis: A Novel Mechanism of Artemisinin and its Derivatives in Cancer Therapy
Current Medicinal Chemistry Pharmacological Activation of Protein Phosphatase 2 A (PP2A): A Novel Strategy to Fight Against Human Malignancies?
Current Medicinal Chemistry Herpesvirus Saimiri-Based Gene Delivery Vectors
Current Gene Therapy Advancements in Adjuvanticity of Bioactive Inorganic and Organic Compounds
Endocrine, Metabolic & Immune Disorders - Drug Targets Stem Cell Defects in Philadelphia Chromosome Negative Chronic Myeloproliferative Disorders: A Phenotypic and Molecular Puzzle?
Current Stem Cell Research & Therapy