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. Mol Cancer Ther; 16(9); 1–8. ©2017 AACR.

中文翻译：

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HPV驱动宫颈癌对Aurora激酶抑制剂的敏感性需要Aurora A和Aurora B的抑制作用

已经报道了Aurora抑制剂的活性和功效在多种癌症类型中。最著名的Aurora抑制剂是alisertib，这是一种研究性Aurora抑制剂，已经成为30多个临床试验的对象。尽管Alisertib被认为主要是体内的Aurora A抑制剂，但它同时具有针对Aurora A和B的抑制活性。在这里，我们显示了alisertib在HPV驱动的宫颈癌的临床前模型中体内抑制Aurora A和B，并且在这种疾病背景下，对Aurora A和B的抑制作用提供了该药物在体内的选择性和功效。 。我们还提供了正式证据，表明阿塞塞替尼需要通过有丝分裂进行治疗才能发挥功效，并且不太可能与能促进G2 DNA损伤检查点反应的药物联合使用。这项工作表明，通过Aurora激酶抑制剂有效控制HPV驱动的癌症需要抑制Aurora A和B。分子癌疗法；16（9）; 1–8。©2017 AACR。