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ZD6474 induces growth arrest and apoptosis of human leukemia cells, which is enhanced by concomitant use of a novel MEK inhibitor, AZD6244

Leukemia volume 21, pages 1308–1310 (2007)Cite this article

Clinical studies showed that the remission in AML patients elicited by sunitinib, an FLT3 kinase inhibitor, was partial and of short duration,4 suggesting that the addition of other anticancer compounds may be required. Recently, we have shown that blockade of Akt/mTOR signaling by rapamycin synergistically enhanced sunitinib-mediated growth inhibition of leukemia cells.5 Taken together, concomitant administration of the FLT3 kinase inhibitor and downstream signal pathway inhibitor such as rapamycin, as well as AZD6244, may be a potential treatment strategy. In summary, ZD6474 may be an effective treatment for individuals with AML that possess mutations in receptor tyrosine kinase genes. In addition, the combined administration of ZD6474 and AZD6244 to patients with AML warrants further investigation.

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Acknowledgements

This work was supported in part by Kanae Foundation for the Promotion of the Medical Science, Public Trust of Haraguchi Memorial Cancer Research Fund, AstraZeneca Research Grant and the Fund for Academic Research from Kochi University. HPK is supported by NIH grants, as well as the Inger Fund and the Parker Hughes Trust.

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Authors and Affiliations

  1. Department of Hematology and Respiratory Medicine, Kochi University, Nankoku, Kochi, Japan

    C Nishioka, T Ikezoe, A Takeshita, J Yang, Y Yang, Y Kuwayama, N Komatsu, K Togitani & H Taguchi

  2. Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan

    T Tasaka

  3. Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China

    Y Yang

  4. Department of Hematology and Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA

    H P Koeffler

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  1. C Nishioka
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  2. T Ikezoe
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  3. A Takeshita
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  5. T Tasaka
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  11. H Taguchi
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Correspondence to T Ikezoe.

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Nishioka, C., Ikezoe, T., Takeshita, A. et al. ZD6474 induces growth arrest and apoptosis of human leukemia cells, which is enhanced by concomitant use of a novel MEK inhibitor, AZD6244. Leukemia 21, 1308–1310 (2007). https://doi.org/10.1038/sj.leu.2404647

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