Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump
| Autor: | Kees Nooter, Erik A.C. Wiemer, Mariël Brok, Antonius W. M. Boersma, Gerrit Stoter, Herman Burger, Hans van Tol |
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| Přispěvatelé: | Medical Oncology, Hematology |
| Rok vydání: | 2004 |
| Předmět: |
Drug export
Abcg2 medicine.drug_class Immunology Breast Neoplasms Drug resistance Pharmacology Binding Competitive Biochemistry Piperazines Tyrosine-kinase inhibitor Substrate Specificity SDG 3 - Good Health and Well-being Cell Line Tumor hemic and lymphatic diseases medicine ATP Binding Cassette Transporter Subfamily G Member 2 Humans Carbon Radioisotopes Mitoxantrone biology Imatinib Cell Biology Hematology Mycotoxins medicine.disease Neoplasm Proteins Pyrimidines Imatinib mesylate Doxorubicin Drug Resistance Neoplasm Benzamides Imatinib Mesylate biology.protein ATP-Binding Cassette Transporters Chronic myelogenous leukemia medicine.drug |
| Zdroj: | Blood, 104, 2940-2942. American Society of Hematology |
| ISSN: | 0006-4971 |
| DOI: | 10.1182/blood-2004-04-1398 |
| Popis: | Imatinib mesylate (STI571), a potent tyrosine kinase inhibitor, is successfully used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. However, the intended chronic oral administration of imatinib may lead to development of cellular resistance and subsequent treatment failure. Indeed, several molecular mechanisms leading to imatinib resistance have already been reported, including overexpression of the MDR1/ABCB1 drug pump. We examined whether imatinib is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump that is frequently overexpressed in human tumors. Using a panel of well-defined BCRP-overexpressing cell lines, we provide the first evidence that imatinib is a substrate for BCRP, that it competes with mitoxantrone for drug export, and that BCRP-mediated efflux can be reversed by the fumitremorgin C analog Ko-143. Since BCRP is highly expressed in the gastrointestinal tract, BCRP might not only play a role in cellular resistance of tumor cells but also influence the gastrointestinal absorption of imatinib. |
| Databáze: | OpenAIRE |
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