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  • Inhibition of Aurora A and Aurora B is required for the sensitivity of HPV-driven cervical cancers to Aurora kinase inhibitors

    Author(s)
    Martin, David
    Fallaha, Sora
    Proctor, Martina
    Stevenson, Alexander
    Perrin, Lewis
    McMillan, Nigel
    Gabrielli, Brian
    Griffith University Author(s)
    McMillan, Nigel
    Fallaha, Sora
    Gabrielli, Brian
    Year published
    2017
    Metadata
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    Abstract
    The activity and efficacy of Aurora inhibitors have been reported in a wide range of cancer types. The most prominent Aurora inhibitor is alisertib, an investigational Aurora inhibitor that has been the subject of more than 30 clinical trials. Alisertib has inhibitory activity against both Aurora A and B, although it is considered to be primarily an Aurora A inhibitor in vivo. Here, we show that alisertib inhibits both Aurora A and B in vivo in preclinical models of HPV-driven cervical cancer, and that it is the inhibition of Aurora A and B that provides the selectivity and efficacy of this drug in vivo in this disease ...
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    The activity and efficacy of Aurora inhibitors have been reported in a wide range of cancer types. The most prominent Aurora inhibitor is alisertib, an investigational Aurora inhibitor that has been the subject of more than 30 clinical trials. Alisertib has inhibitory activity against both Aurora A and B, although it is considered to be primarily an Aurora A inhibitor in vivo. Here, we show that alisertib inhibits both Aurora A and B in vivo in preclinical models of HPV-driven cervical cancer, and that it is the inhibition of Aurora A and B that provides the selectivity and efficacy of this drug in vivo in this disease setting. We also present formal evidence that alisertib requires progression through mitosis for its efficacy, and that it is unlikely to combine with drugs that promote a G2 DNA damage checkpoint response. This work demonstrates that inhibition of Aurora A and B is required for effective control of HPV-driven cancers by Aurora kinase inhibitors.
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    Journal Title
    Molecular Cancer Therapeutics
    Volume
    16
    Issue
    9
    DOI
    https://doi.org/10.1158/1535-7163.MCT-17-0159
    Subject
    Oncology and Carcinogenesis not elsewhere classified
    Oncology and Carcinogenesis
    Pharmacology and Pharmaceutical Sciences
    Publication URI
    http://hdl.handle.net/10072/364286
    Collection
    • Journal articles

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