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  • Alpelisib and radiotherapy treatment enhances Alisertib-mediated cervical cancer tumor killing

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    Tayyar503049-Published.pdf (1.521Mb)
    Author(s)
    Tayyar, Yaman
    Idris, Adi
    Vidimce, Josif
    Ferreira, Danyelle Assis
    McMillan, Nigel Aj
    Griffith University Author(s)
    McMillan, Nigel
    Tayyar, Yaman
    Year published
    2021
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    Abstract
    Human papilloma virus (HPV) is the main causative agent in cervical cancers. High-risk HPV cancers, including cervical cancer, are driven by major HPV oncogene, E6 and E7, which promote uncontrolled cell growth and genomic instability. We have previously shown that the presence of HPV E7 sensitizes cells to inhibition of aurora kinases (AURKs), which regulates the control of cell entry into and through mitosis. Such treatment is highly effective at eliminating early tumors and reducing large, late tumors. In addition, the presence of HPV oncogenes also sensitizes cells to inhibition of phosphoinositide 3-kinases (PI3Ks), a ...
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    Human papilloma virus (HPV) is the main causative agent in cervical cancers. High-risk HPV cancers, including cervical cancer, are driven by major HPV oncogene, E6 and E7, which promote uncontrolled cell growth and genomic instability. We have previously shown that the presence of HPV E7 sensitizes cells to inhibition of aurora kinases (AURKs), which regulates the control of cell entry into and through mitosis. Such treatment is highly effective at eliminating early tumors and reducing large, late tumors. In addition, the presence of HPV oncogenes also sensitizes cells to inhibition of phosphoinositide 3-kinases (PI3Ks), a family of enzymes involved in cellular functions such as cell growth and proliferation. Using MLN8237 (Alisertib), an oral, selective inhibitor of AURKs, we investigated whether Alisertib treatment can improve tumor response when combined with either radiotherapy (RT) treatment or with a PI3K inhibitor, BYL719 (Alpelisib). Indeed, both RT and Alpelisib significantly improved Alisertib-mediated tumor killing, and the promising achieved results warrant further development of these combinations, and potentially translating them to the clinics.
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    Journal Title
    American Journal of Cancer Research
    Volume
    11
    Issue
    6
    Publisher URI
    http://www.ajcr.us/AJCR_V11N6.html
    Copyright Statement
    © The Author(s) 2021. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
    Subject
    Oncology and carcinogenesis
    Alisertib
    Alpelisib
    E7
    HPV
    PI3K
    Publication URI
    http://hdl.handle.net/10072/406107
    Collection
    • Journal articles

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