Chung Sua, Sperier Ella, Graciano Kevin, Hu Xiaoping, Guo Hua, Xu Jia
Department of Genetics, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Department of Genetics, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; O'Neal Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Bioorg Chem. 2025 Aug;163:108633. doi: 10.1016/j.bioorg.2025.108633. Epub 2025 May 26.
The Aurora kinases are a family of serine/threonine kinases crucial for regulating mitosis. Overexpression of the Aurora kinases has been reported in multiple cancer types. They play important roles in driving an oncogenic transformation of cancer cells by regulating their survival and proliferation, mainly because of the kinases' mitotic activity. Aurora kinase inhibitors (AKIs) were developed and tested in clinical trials and effectively suppressed many cancer types, suggesting the potential for Aurora kinases as a novel therapeutic target. Aurora kinase inhibition has also been well-documented to enhance chemotherapy effectiveness in various cancers. However, not all cancer types respond to AKIs, and the mechanisms behind the resistance are still elusive. This review will first briefly summarize the gene expression, regulation, and substrates of the Aurora Kinases, describe the function of Aurora kinases in mitosis, and then review the Aurora kinases' oncogenic roles in different cancer types as well as tumorigenesis, including cancer metabolism and anti-tumor immune evasion. In addition, we recapped the recent studies that revealed the critical role of Aurora Kinases in various cancer therapies and discussed the clinical outcomes of AKIs in combination with other types of therapies. Furthermore, we reviewed the current development of a new generation of AKI, such as PROTAC degrader. Further understanding the mechanism underlying the responsiveness of AKIs could help evaluate their effect and improve them as potential therapeutic targets.
极光激酶是一类对调节有丝分裂至关重要的丝氨酸/苏氨酸激酶。在多种癌症类型中均有报道极光激酶的过表达。它们通过调节癌细胞的存活和增殖，在驱动癌细胞的致癌转化中发挥重要作用，主要是由于这些激酶的有丝分裂活性。极光激酶抑制剂（AKIs）已被研发并在临床试验中进行测试，可有效抑制多种癌症类型，这表明极光激酶作为一种新型治疗靶点具有潜力。极光激酶抑制作用也已被充分证明可增强各种癌症的化疗效果。然而，并非所有癌症类型都对AKIs有反应，其耐药机制仍不清楚。本综述将首先简要总结极光激酶的基因表达、调控及底物，描述极光激酶在有丝分裂中的功能，然后综述极光激酶在不同癌症类型中的致癌作用以及肿瘤发生过程，包括癌症代谢和抗肿瘤免疫逃逸。此外，我们回顾了最近揭示极光激酶在各种癌症治疗中关键作用的研究，并讨论了AKIs与其他类型疗法联合使用的临床结果。此外，我们还综述了新一代AKI（如PROTAC降解剂）的当前进展。进一步了解AKIs反应性的潜在机制有助于评估其效果，并将其作为潜在治疗靶点加以改进。
