Nilotinib and imatinib inhibit cytarabine cellular uptake: implications for combination therapy.
The tyrosine kinase inhibitor (TKI) imatinib has been used for a decade to treat chronic myeloid leukemia (CML). A very efficient response is obtained with patients in chronic phase, but its efficacy in late phase patients is often transient. The combination of imatinib or of the new TKI nilotinib with cytarabine is a new treatment approach proposed for CML. We have investigated the effect of imatinib and nilotinib on cytarabine uptake, and have found that both molecules inhibit cytarabine transport. These results should impact on the design of clinical trials that investigate the combination of TKIs and nucleoside analogs.
Centre de Recherche en Cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, Centre Hospitalier Universitaire de Québec, Québec, Canada.
Josy S
JS
Naud
Karim
K
Ghani
Pedro O
PO
de Campos-Lima
Manuel
M
Caruso
D001549:Benzamides; D003561:Cytarabine / Q000378:metabolism*; D004359:Drug Therapy, Combination; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D003561:Cytarabine; D000068877:Imatinib Mesylate; C498826:nilotinib; D013936:Thymidine