Aurora kinase inhibitors as anticancer molecules.
Aurora kinase inhibitors as anticancer molecules.
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DOI：
10.1016/j.bbagrm.2010.09.004
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发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
Sen S
中科院分区：
文献类型：
--
作者：
Katayama H;Sen S
丝氨酸/苏氨酸激酶的Aurora激酶家族是有丝分裂的重要调节因子，其经常在人类癌症中过表达，并且已经涉及致癌转化，包括癌细胞中染色体不稳定性的发展。在人类中，在激酶家族的三个成员Aurora-A、-B和-C中，只有Aurora-A和-B在经历有丝分裂细胞分裂的体细胞中以可检测的水平表达，并且已经更详细地表征了它们参与与癌症相关表型的发展相关的细胞途径。Aurora-A和B正被研究作为抗癌治疗的潜在靶点。由于Aurora激酶的异常表达导致染色体不稳定和多种肿瘤抑制因子和癌蛋白调节途径的紊乱，因此开发Aurora激酶抑制剂作为抗癌分子受到关注。多种Aurora激酶抑制剂作为靶向抗癌药物的临床前研究和早期I期和II期临床试验提供了令人鼓舞的结果。本文讨论了极光激酶-A和-B在调节癌症相关细胞表型的功能参与，以及一些更好的特点极光激酶抑制剂在调节极光激酶的功能相互作用的研究结果。本文还讨论了开发下一代Aurora激酶抑制剂及其作为抗癌治疗药物的临床应用前景。
Aurora kinase family of serine/threonine kinases are important regulators of mitosis that are frequently over expressed in human cancers and have been implicated in oncogenic transformation including development of chromosomal instability in cancer cells. In humans, among the three members of the kinase family, Aurora-A, -B and -C, only Aurora-A and -B are expressed in detectable levels in somatic cells undergoing mitotic cell division and have been characterized in greater detail for their involvement in cellular pathways relevant to the development of cancer associated phenotypes. Aurora-A and -B are being investigated as potential targets for anticancer therapy. Development of inhibitors against Aurora kinases as anticancer molecules gained attention because of the facts that aberrant expression of these kinases lead to chromosomal instability and derangement of multiple tumor suppressor and oncoprotein regulated pathways. Pre-clinical studies and early phase I and II clinical trials of multiple Aurora kinase inhibitors as targeted anticancer drugs have provided encouraging results. This article discusses functional involvement of Aurora kinase-A and -B in the regulation of cancer relevant cellular phenotypes together with findings on some of the better characterized Aurora kinase inhibitors in modulating the functional interactions of Aurora kinases. Future possibilities about developing next generation Aurora kinase inhibitors and their clinical utility as anticancer therapeutic drugs are also discussed.