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Pharmacokinetic Resistance to Imatinib Mesylate: Role of the ABC Drug Pumps ABCG2 (BCRP) and ABCB1 (MDR1) in the Oral Bioavailability of Imatinib

Imatinib mesylate is a selective tyrosine kinase inhibitor that is successfully used in the treatment of chronic myeloid leukaemias and gastrointestinal stromal tumours. The drug is taken orally on a daily basis in order to suppress tumour growth. Unfortunately, the vast majority of patients will eventually progress while on therapy. It is generally thought that this acquired unresponsiveness is due to gene amplification or somatic mutations in the drug’s target genes. However, we have now evidence, based on several in vitro and in vivo observations suggesting that pharmacokinetic resistance may also play a definitive role in the ultimate resistance of patients on chronic imatinib. Our findings may have serious implications for the chronic imatinib treatment of cancer patients.