Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 1255 Light Hall, 2215 Garland Avenue, Nashville, TN 37232, USA.
Mol Cancer Ther. 2010 Feb;9(2):268-78. doi: 10.1158/1535-7163.MCT-09-0765. Epub 2010 Feb 2.
Standard therapeutic approaches of cytotoxics and radiation in cancer are not only highly toxic, but also of limited efficacy in treatment of a significant number of cancer patients. The molecular analysis of the cancer genomes have shown a remarkable complexity and pointed to key genomic and epigenomic alterations in cancer. These discoveries are paving the way for targeted therapy approaches. However, although there are a large number of potential targets, only a few can regulate key cellular functions and intersect multiple signaling networks. The Aurora kinase family members (A, B, and C) are a collection of highly related and conserved serine-threonine kinases that fulfill these criteria, being key regulators of mitosis and multiple signaling pathways. Alterations in Aurora kinase signaling are associated with mitotic errors and have been closely linked to chromosomal aneuploidy in cancer cells. Several studies have shown amplification and/or overexpression of Aurora kinase A and B in hematologic malignancies and solid tumors. Over the past several years, Aurora kinases have become attractive targets. Several ongoing clinical trials and bench-based research are assessing the unique therapeutic potential of Aurora-based targeted therapy.
癌症的细胞毒性药物和放射治疗的标准治疗方法不仅毒性很高，而且对相当数量的癌症患者的治疗效果有限。对癌症基因组的分子分析显示出显著的复杂性，并指出了癌症中的关键基因组和表观基因组改变。这些发现为靶向治疗方法铺平了道路。然而，尽管有大量的潜在靶点，但只有少数靶点可以调节关键的细胞功能并交叉多个信号网络。极光激酶家族成员（A、B 和 C）是一组高度相关和保守的丝氨酸-苏氨酸激酶，满足这些标准，是有丝分裂和多种信号通路的关键调节剂。极光激酶信号的改变与有丝分裂错误有关，并与癌细胞中的染色体非整倍性密切相关。多项研究表明，血液恶性肿瘤和实体瘤中极光激酶 A 和 B 的扩增和/或过表达。在过去的几年中，极光激酶已成为有吸引力的靶点。目前正在进行的一些临床试验和基础研究正在评估基于极光激酶的靶向治疗的独特治疗潜力。
