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• W2024051063 abstract "Breast cancer resistance protein (BCRP) is a half‐molecule ATP‐binding cassette transporter that forms a functional homodimer and pumps out various anticancer agents, such as 7‐ethyl‐10‐hydroxycamptothecin, topotecan, mitoxantrone and flavopiridol, from cells. Estrogens, such as estrone and 17β‐estradiol, have been found to restore drug sensitivity levels in BCRP ‐transduced cells by increasing the cellular accumulation of such agents. Furthermore, synthetic estrogens, tamoxifen derivatives and phytoestrogens/flavonoids have now been identified that can effectively circumvent BCRP‐mediated drug resistance. Transcellular transport experiments have shown that BCRP transports sulfated estrogens and various sulfated steroidal compounds, but not free estrogens. The kinase inhibitor gefitinib inhibited the transporter function of BCRP and reversed BCRP‐mediated drug resistance both in vitro and in vivo . BCRP ‐transduced human epidermoid carcinoma A431 (A431/BCRP) and BCRP ‐transduced human non‐small cell lung cancer PC‐9 (PC‐9/BCRP) cells showed gefitinib resistance. Physiological concentrations of estrogens (10–100 pM) reduced BCRP protein expression without affecting its mRNA levels. Two functional polymorphisms of the BCRP gene have been identified. The C376T (Q126Stop) polymorphism has a dramatic phenotype as active BCRP protein cannot be expressed from a C376T allele. The C421A (Q141K) polymorphism is also significant as Q141K ‐BCRP ‐transfected cells show markedly low protein expression levels and low‐level drug resistance. Hence, individuals with C376T or C421A polymorphisms may express low levels of BCRP or none at all, resulting in hypersensitivity of normal cells to BCRP‐substrate anticancer agents. In summary, both modulators of BCRP and functional single nucleotide polymorphisms within the BCRP gene affect the transporter function of the protein and thus can modulate drug sensitivity and substrate pharmacokinetics and pharmacodynamics in affected cells and individuals. ( Cancer Sci 2005; 96: 457–465)" @default.
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• W2024051063 date "2005-08-01" @default.
• W2024051063 modified "2023-10-14" @default.
• W2024051063 title "Breast cancer resistance protein: Molecular target for anticancer drug resistance and pharmacokinetics/pharmacodynamics" @default.
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• W2024051063 doi "https://doi.org/10.1111/j.1349-7006.2005.00081.x" @default.
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