Department of Medical Oncology and Cancer Genomics Centre, UMC Utrecht, Universiteitsweg 100, Stratenum 2. 118, Utrecht 3584 CG, The Netherlands.
Nat Rev Cancer. 2010 Dec;10(12):825-41. doi: 10.1038/nrc2964. Epub 2010 Nov 24.
Large numbers of inhibitors for polo-like kinases and aurora kinases are currently being evaluated as anticancer drugs. Interest in these drugs is fuelled by the idea that these kinases have unique functions in mitosis. Within the polo-like kinase family, the emphasis for targeted therapies has been on polo-like kinase 1 (PLK1), and in the aurora kinase family drugs have been developed to specifically target aurora kinase A (AURKA; also known as STK6) and/or aurora kinase B (AURKB; also known as STK12). Information on the selectivity of these compounds in vivo is limited, but it is likely that off-target effects within the same kinase families will affect efficacy and toxicity profiles. In addition, it is becoming clear that interplay between polo-like kinases and aurora kinases is much more extensive than initially anticipated, and that both kinase families are important factors in the response to classical chemotherapeutics that damage the genome or the mitotic spindle. In this Review we discuss the implications of these novel insights on the clinical applicability of polo-like kinase and aurora kinase inhibitors.
目前,大量的 polo 样激酶和极光激酶抑制剂正在被评估为抗癌药物。这些药物之所以受到关注,是因为人们认为这些激酶在有丝分裂中具有独特的功能。在 polo 样激酶家族中,靶向治疗的重点是 polo 样激酶 1(PLK1),而在极光激酶家族中,已经开发出了针对极光激酶 A(AURKA;也称为 STK6)和/或极光激酶 B(AURKB;也称为 STK12)的药物。这些化合物在体内的选择性信息有限,但同一激酶家族中的脱靶效应可能会影响疗效和毒性特征。此外,越来越明显的是,polo 样激酶和极光激酶之间的相互作用比最初预期的要广泛得多,而且这两个激酶家族都是对破坏基因组或有丝分裂纺锤体的经典化疗药物产生反应的重要因素。在这篇综述中,我们讨论了这些新的见解对 polo 样激酶和极光激酶抑制剂的临床应用的影响。