The selective Aurora B kinase inhibitor AZD1152 is a potential new treatment for multiple myeloma

被引：51

作者：

Evans, Robert P. ^{[1
]}

Naber, Claudia ^{[1
]}

Steffler, Tara Summary ^{[1
]}

Checkland, Tamara ^{[1
]}

Maxwell, Christopher A. ^{[1
]}

Keats, Jonathan J. ^{[1
]}

Belch, Andrew R. ^{[1
]}

Pilarski, Linda M. ^{[1
]}

Lai, Raymond ^{[1
]}

Reiman, Tony ^{[1
]}

机构：

[1] Univ Alberta, Dept Oncol, Cross Canc Inst, Edmonton, AB, Canada

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2008年 / 140卷 / 03期

关键词：

multiple myeloma; AZD1152; Auora B kinase; novel therapeutics;

D O I：

10.1111/j.1365-2141.2007.06913.x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aurora kinases are potential targets for cancer therapy. Previous studies have validated Aurora kinase A as a therapeutic target in multiple myeloma (MM), and have demonstrated in vitro anti-myeloma effects of small molecule Aurora kinase inhibitors that inhibit both Aurora A and B. This study demonstrated that Aurora B kinase was strongly expressed in myeloma cell lines and primary plasma cells. The selective Aurora B inhibitor AD1152-induced apoptotic death in myeloma cell lines at nanomolar concentrations, with a cell cycle phenotype consistent with that reported previously for Aurora B inhibition. In some cases, AZD1152 in combination with dexamethasone showed increased anti-myeloma activity compared with the use of either agent alone. AZD1152 was active against sorted CD138(+) BM plasma cells from myeloma patients but also, as expected, was toxic to CD138(-) marrow cells from the same patients. In a murine myeloma xenograft model, AZD1152-inhibited tumour growth at well-tolerated doses and induced cell death in established tumours, with associated mild, transient leucopenia. AZD1152 shows promise in these preclinical studies as a novel treatment for MM.

引用

页码：295 / 302

页数：8