Aurora kinase inhibitors: identification and preclinical validation of their biomarkers

被引：57

作者：

Carpinelli, Patrizia ^{[1
]}

Moll, Juergen ^{[1
]}

机构：

[1] Nerviano Med Sci, I-20014 Nerviano, MI, Italy

来源：

EXPERT OPINION ON THERAPEUTIC TARGETS | 2008年 / 12卷 / 01期

关键词：

aurora kinases; biomarkers; cancer; small-molecule inhibitors;

D O I：

10.1517/14728222.12.1.69

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Aurora kinases are key regulators of mitosis and inhibitors being developed by a wide range of pharmaceutical and biotechnology companies for the treatment of cancer. Tumor cells respond differentially on inhibition of different Aurora kinase family members and these differences have to be considered in the clinical development of small-molecule inhibitors with respect to the chosen indications, the schedules or the selection of appropriate end points and they should also guide the development of biomarkers. Preclinical validation of potential biomarkers for Aurora kinase inhibitors led to a first application in clinical trials, as exemplified for the phosphorylation of histone H3 to follow Aurora-B inhibition. This review discusses the criteria for translation into the clinic and the value of pharmacodynamic biomarkers and their potential, but also their limitations to be used as surrogate markers for clinical end points.

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收藏

页码：69 / 80

页数：12

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