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    Progress towards a clinically-successful ATR inhibitor for cancer therapy

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    Publication date
    2021-02
    Author
    Barnieh, Francis M.
    Loadman, Paul M.
    Falconer, Robert A.
    Keyword
    DDR
    ATR
    ATM
    ATR inhibitors
    Chemo- and radiosensitisers
    Rights
    (c) 2021 Crown Copyright. This is an Open Access article distributed under the Creative Commons CC-BY-NC license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
    Peer-Reviewed
    Yes
    Open Access status
    Green
    
    Metadata
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    Abstract
    The DNA damage response (DDR) is now known to play an important role in both cancer development and its treatment. Targeting proteins such as ATR (Ataxia telangiectasia mutated and Rad3-related) kinase, a major regulator of DDR, has demonstrated significant therapeutic potential in cancer treatment, with ATR inhibitors having shown anti-tumour activity not just monotherapies, but also in potentiating the effects of conventional chemotherapy, radiotherapy, and immunotherapy. This review focuses on the biology of ATR, its functional role in cancer development and treatment, and the rationale behind inhibition of this target as a therapeutic approach, including evaluation of the progress and current status of development of potent and specific ATR inhibitors that have emerged in recent decades. The current applications of these inhibitors both in preclinical and clinical studies either as single agents or in combinations with chemotherapy, radiotherapy and immunotherapy are also extensively discussed. This review concludes with some insights into the various concerns raised or observed with ATR inhibition in both the preclinical and clinical settings, with some suggested solutions.
    URI
    http://hdl.handle.net/10454/18345
    Version
    Published version
    Citation
    Barnieh FM, Loadman PM and Falconer RA (2021) Progress towards a clinically-successful ATR inhibitor for cancer therapy. Current Research in Pharmacology and Drug Discovery. 2: 100017.
    Link to publisher’s version
    https://doi.org/10.1016/j.crphar.2021.100017
    Type
    Article
    Collections
    Life Sciences Publications

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