The human breast cancer resistance protein (BCRP/ABCG2) is the second member of the G subfamily of the large ATP-binding cassette (ABC) transporter superfamily. BCRP was initially discovered in multidrug resistant breast cancer cell lines where it confers resistance to chemotherapeutic agents such as mitoxantrone, topotecan and methotrexate by extruding these compounds out of the cell. BCRP is capable of transporting non-chemotherapy drugs and xenobiotiocs as well, including nitrofurantoin, prazosin, glyburide, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. BCRP is frequently detected at high levels in stem cells, likely providing xenobiotic protection. BCRP is also highly expressed in normal human tissues including the small intestine, liver, brain endothelium, and placenta. Therefore, BCRP has been increasingly recognized for its important role in the absorption, elimination, and tissue distribution of drugs and xenobiotics.

A Review of Human Breast Cancer Resistant Protein—BCRP

BCRP (The human breast cancer resistant protein) is an ATP-binding cassette (ABC) transporter, which together with two other ABC efflux drug pumps, namely P-glycoprotein (P-gp, ABCB1) and multidrug resistance-related protein 1 (MRP1, ABCC1) is the most important multidrug resistance protein found in eukaryotic cells, including cells in the testis. Breast cancer resistance protein (BCRP/ABCG2) is known to localize at the blood-brain barrier (BBB) and can significantly restrict xenobiotic permeability in the brain.

BCRP inhibitor

Specific inhibitors have inhibitory effects on BCRP. FTA, a mycotoxin fumitremorgin C, was first reported to reverse the resistance to adriamycin Mx mediated by BCRP, but has no effect on P-gp and MRP-mediated resistance. It can increase the resistance of CF-7/ABCG2 cells to mitoxantrone and adriamycin. The sensitivity of topotecan and the inhibition of ATPase activity of insect cell membrane enriched with ABCG2R482G mutant. Some topotecan derivatives are also specific inhibitors of ABCG2. For example, neomycin reversed the drug resistance to topotecan, mitoxene and SN-38 in vitro cell line, and competitively inhibited topotecan external pump. Synthetic yew derivatives. For example, BAY59-8862IIDN-5109, the inhibitory effect of mitoxantrone efflux is weaker than that of FTC (follicular thyroid cancer), It can only inhibit wild-type ABCG2 (R482), but not variant ABCG2 (R482T). Flavonoids and their derivatives such as 5, 7-dihydroflavone and biochanin A are the most potent inhibitors. The activated cysteine residues can also be used as inhibitors.

Clinical significance of BCRP

BCRP has been reported in breast cancer, lung cancer, leukemia and other malignant tumors. Studies have shown that the high expression of BCRP leads to the occurrence of clinical drug resistance, which is a poor prognostic factor for acute leukemia. In elderly patients with non-small cell lung cancer, BCRP can be used as an indicator of the efficacy of chemotherapy. Genomics can be used to measure the response of each individual to a certain drug therapy, which can guide drug use and improve clinical prognosis.


Wu Xiang Meng, Sheng Li, Jia Yufei, Li Yan. The role of Drug-resistant proteins in Pharmacokinetics of Breast Cancer [J]. Journal of Pharmacology: 1368-1377 (09): 1368-1377.

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