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Aurora kinase inhibitors: which role in the treatment of chronic myelogenous leukemia patients resistant to imatinib?

Giovanni Martinelli, Simona Soverini, Ilaria Iacobucci, Cristina Papayannidis, Daniela Cilloni, Michele Baccarani
  • Simona Soverini
    Department of Hematology/Oncology “L. and A. Seràgnoli”, University of Bologna, Italy
  • Ilaria Iacobucci
    Department of Hematology/Oncology “L. and A. Seràgnoli”, University of Bologna, Italy
  • Cristina Papayannidis
    Department of Hematology/Oncology “L. and A. Seràgnoli”, University of Bologna, Italy
  • Daniela Cilloni
    Division of Hematology and Internal Medicine, Department of Clinical and Biological Science, University of Turin, Italy
  • Michele Baccarani
    Department of Hematology/Oncology “L. and A. Seràgnoli”, University of Bologna, Italy

Abstract

At present, there are no compounds in clinical development in the field of chronic myeloid leukemia (CML) or Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) that have been documented to harbor significant activity against the imatinib-resistant T315I mutation. Recent reports on the pre-clinical activity of some emerging tyrosine kinase inhibitors such as ON012380, VX-680 and PHA-739358 promise possible clinical efficacy against this specific Bcr-Abl mutant form. Here, we focus on the role of aurora kinase inhibitor VX-680 and PHA-739358 in blocking the leukemogenic pathways driven by wild-type and T315I-Bcr-Abl in CML or Ph+ ALL by reviewing recent research evidence. We also discuss the possibility of employing aurora kinase inhibitors as a promising new therapeutic approach in the treatment of CML and Ph+ ALL patients resistant to first and second generation TK inhibitors.

Keywords

Aurora kinase inhibitors; Chronic Myelogenous Leukemia

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Submitted: 2009-01-13 17:24:19
Published: 2009-02-18 10:29:52
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