Aurora kinase inhibitors--rising stars in cancer therapeutics?
Aurora kinase inhibitors--rising stars in cancer therapeutics?
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DOI：
10.1158/1535-7163.mct-09-0765
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发表时间：
2010-02
影响因子：
5.7
通讯作者：
El-Rifai W
中科院分区：
文献类型：
--
作者：
Dar AA;Goff LW;Majid S;Berlin J;El-Rifai W
癌症中细胞毒素和放射的标准治疗方法不仅毒性很强，而且在治疗大量癌症患者时疗效有限。对癌症基因组的分子分析显示出显著的复杂性，并指出了癌症中关键的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，尽管有大量潜在的靶点，但只有少数能够调节关键的细胞功能并与多个信号网络相互交叉。极光激酶家族成员（A、B和C）是一组高度相关且保守的丝氨酸/苏氨酸激酶，符合这些标准，是有丝分裂和多个信号通路的关键调节因子。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。几项研究表明，在血液系统恶性肿瘤和实体瘤中，极光激酶A和B存在扩增和/或过度表达。在过去几年中，极光激酶已成为有吸引力的靶点。几项正在进行的临床试验和基于实验室的研究正在评估基于极光的靶向治疗的独特治疗潜力。
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, while 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 over-expression 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.