AURKA 作为一种重要的有丝分裂激酶而闻名。最近的研究结果还证实了其在许多其他生物过程中的关键作用，包括纤毛发生、线粒体动力学、神经元生长、DNA 复制和细胞周期进展。 AURKA 在许多癌症中过度表达与不良预后和生存密切相关。目前，AURKA 靶向药物尚未获得批准，部分原因是相关的附带毒性，部分原因是其作为单一药物在多种肿瘤中的疗效有限。从机制上讲，AURKA 过度表达使其能够磷酸化许多病理底物，从而促进高度侵袭性的致癌表型。我们的综述考察了 AURKA 调控的最新进展，重点关注 AURKA 的 33 个此类直接癌症特异性靶标及其相关的致癌信号级联。出现的常见主题之一是 AURKA 经常参与与其底物的反馈循环，这可能是导致其在癌细胞中持续上调和过度激活的决定性因素，这是以前未曾利用过的致命弱点。 AURKA 及其底物之间的这种动态相互作用为靶向治疗干预提供了潜在的机会。通过靶向这些底物，有可能破坏这种反馈回路，从而有效逆转 AURKA 水平，从而为开发更安全的 AURKA 靶向疗法提供有希望的途径。此外，探索 AURKA 抑制与其其他致癌和/或肿瘤抑制靶点的协同效应可以为开发针对 AURKA 驱动的癌症的有效联合疗法提供进一步的机会，从而最大限度地发挥其作为关键药物靶点的潜力。© 2024。作者（s）。

AURKA is predominantly famous as an essential mitotic kinase. Recent findings have also established its critical role in a plethora of other biological processes including ciliogenesis, mitochondrial dynamics, neuronal outgrowth, DNA replication and cell cycle progression. AURKA overexpression in numerous cancers is strongly associated with poor prognosis and survival. Still no AURKA-targeted drug has been approved yet, partially because of the associated collateral toxicity and partly due to its limited efficacy as a single agent in a wide range of tumors. Mechanistically, AURKA overexpression allows it to phosphorylate numerous pathological substrates promoting highly aggressive oncogenic phenotypes. Our review examines the most recent advances in AURKA regulation and focuses on 33 such direct cancer-specific targets of AURKA and their associated oncogenic signaling cascades. One of the common themes that emerge is that AURKA is often involved in a feedback loop with its substrates, which could be the decisive factor causing its sustained upregulation and hyperactivation in cancer cells, an Achilles heel not exploited before. This dynamic interplay between AURKA and its substrates offers potential opportunities for targeted therapeutic interventions. By targeting these substrates, it may be possible to disrupt this feedback loop to effectively reverse AURKA levels, thereby providing a promising avenue for developing safer AURKA-targeted therapeutics. Additionally, exploring the synergistic effects of AURKA inhibition with its other oncogenic and/or tumor-suppressor targets could provide further opportunities for developing effective combination therapies against AURKA-driven cancers, thereby maximizing its potential as a critical drug target.© 2024. The Author(s).