Alpelisib and radiotherapy treatment enhances Alisertib-mediated cervical cancer tumor killing
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Idris, Adi
Vidimce, Josif
Ferreira, Danyelle Assis
McMillan, Nigel Aj
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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 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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American Journal of Cancer Research
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11
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6
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© 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.
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Oncology and carcinogenesis
Biochemistry and cell biology
Alisertib
Alpelisib
E7
HPV
PI3K
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Tayyar, Y; Idris, A; Vidimce, J; Ferreira, DA; McMillan, NA, Alpelisib and radiotherapy treatment enhances Alisertib-mediated cervical cancer tumor killing, American Journal of Cancer Research, 2021, 11 (6), pp. 3240-3251