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The selective Aurora B kinase inhibitor AZD1152 is a potential new treatment for multiple myeloma
Author(s) -
Evans Robert P.,
Naber Claudia,
Steffler Tara,
Checkland Tamara,
Maxwell Christopher A.,
Keats Jonathan J.,
Belch Andrew R.,
Pilarski Linda M.,
Lai Raymond,
Reiman Tony
Publication year - 2008
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2007.06913.x
Subject(s) - aurora inhibitor , aurora b kinase , aurora kinase , multiple myeloma , plasma cell myeloma , aurora a kinase , cancer research , apoptosis , kinase , medicine , cell cycle , biology , cell , cancer , cytokinesis , microbiology and biotechnology , cell division , biochemistry
Summary 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 AZD1152‐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.