Journal
CANCER LETTERS
Volume 328, Issue 2, Pages 307-317Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2012.10.001
Keywords
ABC transporters; ABCB1/P-gp; ABCC10/MRP7; ABCG2/BCRP; Nilotinib; Multidrug resistance
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Funding
- National Institutes of Health [1R15CA143701]
- St. John's University Seed Grant [579-1110]
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A panel of clinically used tyrosine kinase inhibitors were compared and nilotinib was found to most potently sensitize specific anticancer agents by blocking the functions of ABCB1/P-glycoprotein, ABCG2/BCRP and ABCC10/MRP7 transporters involved in multi-drug resistance. Nilotinib appreciably enhanced the antitumor response of (1) paclitaxel in the ABCB1- and novel ABCC10-xenograft models, and (2) doxorubicin in a novel ABCG2-xenograft model. With no apparent toxicity observed in the above models, nilotinib attenuated tumor growth synergistically and increased paclitaxel concentrations in ABCB1-overexpressing tumors. The beneficial actions of nilotinib warrant consideration as viable combinations in the clinic with agents that suffer from MDR-mediated insensitivity. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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