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Nilotinib-mediated inhibition of ABCB1 increases intracellular concentration of dasatinib in CML cells: implications for combination TKI therapy

Leukemia volume 24, pages 658–660 (2010)Cite this article

We read with interest the recently published article by Davies et al.1 In this study they found nilotinib to be an inhibitor, but not a substrate of ABCB1 and ABCG2.1 We and others have previously demonstrated that dasatinib is a substrate of ABCB12, 3 and ABCG2.2 Based on our and Davies et al.'s1 findings, we speculate that a combination of nilotinib and dasatinib may be synergistic, as nilotinib-mediated inhibition of ABCB1 and ABCG2 may enhance the intracellular uptake and retention (IUR) of dasatinib. This would be analogous to the earlier described4 synergy between nilotinib and imatinib, which we speculated to be due to an imatinib-mediated increase in nilotinib IUR.5

According to Davies et al.,1 nilotinib is also an ABCG2 inhibitor; however, in our study, nilotinib did not increase dasatinib IUR (19.74±2.86 vs 23.40±2.25; P=0.1) in K562-ABCG2 cell line (ABCG2-overexpressing cell line).

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References

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Authors and Affiliations

  1. Division of Haematology, SA Pathology, Adelaide, South Australia, Australia

    D K Hiwase, D White, S Zrim, V Saunders, J V Melo & T P Hughes

  2. Department of Medicine, Faculty of Health Science, University of Adelaide, Adelaide, South Australia, Australia

    D K Hiwase, D White, J V Melo & T P Hughes

  3. Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, Australia

    D K Hiwase, D White, S Zrim, V Saunders, J V Melo & T P Hughes

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  1. D K Hiwase
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Correspondence to T P Hughes.

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Hiwase, D., White, D., Zrim, S. et al. Nilotinib-mediated inhibition of ABCB1 increases intracellular concentration of dasatinib in CML cells: implications for combination TKI therapy. Leukemia 24, 658–660 (2010). https://doi.org/10.1038/leu.2009.242

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