Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Lancet Oncol. 2013 Sep;14(10):e425-35. doi: 10.1016/S1470-2045(13)70128-1.
In healthy cells, controlled activation of aurora kinases regulates mitosis. Overexpression and hyperactivation of aurora kinases A and B have major roles in tumorigenesis, and can induce aneuploidy and genomic instability. In squamous-cell carcinomas of the head and neck, overexpression of aurora kinase A is associated with decreased survival, and a reduction in aurora kinase A and aurora kinase B expression inhibits cell growth and increases apoptosis. In this Review, we provide an overview of the biological functions of aurora kinases in healthy cells and in cancer cells, and we review small studies and high-throughput datasets that particularly implicate aurora kinase A in the pathogenesis of squamous-cell carcinomas of the head and neck. Early phase trials are beginning to assess the activity of small-molecule inhibitors of aurora kinases. We summarise trials of aurora kinase inhibitors in squamous-cell carcinomas of the head and neck, and discuss directions for future drug combination trials and biomarkers to use with drugs that inhibit aurora kinases.
在健康细胞中，极光激酶的受控激活调节有丝分裂。极光激酶 A 和 B 的过表达和过度激活在肿瘤发生中起主要作用，并可诱导非整倍体和基因组不稳定性。在头颈部鳞状细胞癌中，极光激酶 A 的过表达与生存率降低有关，而降低极光激酶 A 和极光激酶 B 的表达可抑制细胞生长并增加细胞凋亡。在这篇综述中，我们概述了极光激酶在健康细胞和癌细胞中的生物学功能，并回顾了特别表明极光激酶 A 参与头颈部鳞状细胞癌发病机制的小型研究和高通量数据集。早期阶段的试验开始评估小分子极光激酶抑制剂的活性。我们总结了头颈部鳞状细胞癌中极光激酶抑制剂的试验，并讨论了未来药物联合试验和使用抑制极光激酶的药物的生物标志物的方向。
