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The combination of VE-465 and vincristine, the potential therapy for leukemia

     Leukemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of white blood cells, and studies on the treatment of the disease have been carried out for many years. At present, a variety of small-molecule agents targeting specific leukemogenetic molecules have been used in preclinical or clinical treatment of leukemia. For example, BCR/ABL kinase inhibitors, including imatinib, nilotinib and dasatinib have shown the effective treatment against BCR/ABL-positive leukemia. However, novel agents and therapy may be still needed, since monotherapy shows only limited clinical efficacy.

     Aurora kinases play a crucial role in cellular division by controlling chromatid segregation, and thus are essential for cell proliferation. Some studies have demonstrated that inhibition of aurora kinase activity will induce blockage of the cell cycle, resulting in suppression of tumor cell proliferation. For example, the inhibitor of aurora kinase, MK-0457, have been reported to exhibit a anti-leukemia activity against imatinib-resistant leukemia cells[1].
     In the latest paper by Yoshida et al., VE-465, as a specific aurora kinase inhibitor, is found to effectively inhibited cell growth in various human leukemia cell lines in combination with vincristine. The mechanism studies indicated that vincristine enhanced the VE-465-mediated induction of apoptosis by activation of the caspase pathway through ERK1/2 phosphorylation[2].
     In summary, some inhibitors of aurora kinases, such as VE-465 show effective inhibition against leukemia, and the combination of VE-465 and vincristine represents a potential therapy for myeloid leukemia.

Reference
[1]. Nat Med 2004;10:262–7.
[2]. Biochem Pharmacol (2011), doi:10.1016/j.bcp.2011.09.015

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