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

Robert P Evans1, Claudia Naber, Tara Steffler

  • 1Department of Oncology, University of Alberta/Cross Cancer Institute, Edmonton, AB, Canada.

British Journal of Haematology
|December 14, 2007
PubMed

Insights

Selective Aurora B kinase inhibition with AZD1152 shows promise for treating multiple myeloma (MM). This inhibitor induced cancer cell death and reduced tumor growth in preclinical models, suggesting a potential new therapy for MM.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Aurora kinases are crucial for cell division and are implicated in cancer development.
  • Aurora kinase A is a validated therapeutic target in multiple myeloma (MM).
  • Small molecule inhibitors targeting both Aurora A and B kinases have shown in vitro anti-myeloma effects.

Purpose of the Study:

  • To investigate the efficacy of a selective Aurora B kinase inhibitor, AZD1152, in preclinical models of multiple myeloma.
  • To evaluate the expression of Aurora B kinase in myeloma cells.
  • To assess the combination therapy of AZD1152 with dexamethasone.

Main Methods:

  • Assessed Aurora B kinase expression in myeloma cell lines and primary patient cells.
  • Treated myeloma cell lines with AZD1152 and evaluated cell death and cell cycle.
  • Administered AZD1152 alone and in combination with dexamethasone to patient-derived cells.
  • Tested AZD1152 in a murine myeloma xenograft model.
  • Evaluated toxicity in patient-derived bone marrow cells and in the murine model.

Main Results:

  • Aurora B kinase was highly expressed in myeloma cell lines and primary plasma cells.
  • AZD1152 induced apoptotic death in myeloma cells at nanomolar concentrations.
  • Combination of AZD1152 and dexamethasone demonstrated enhanced anti-myeloma activity in some cases.
  • AZD1152 showed activity against patient-derived myeloma cells but also toxicity to normal marrow cells.
  • AZD1152 inhibited tumor growth and induced cell death in a murine myeloma xenograft model at well-tolerated doses, with transient leucopenia.

Conclusions:

  • Selective Aurora B inhibition with AZD1152 is a promising therapeutic strategy for multiple myeloma.
  • AZD1152 demonstrates preclinical efficacy against myeloma cells and tumors.
  • Further investigation into AZD1152 as a novel treatment for MM is warranted.

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