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Clinical Cancer Drugs
ISSN (Print): 2212-697X
ISSN (Online): 2212-6988
VOLUME: 1
ISSUE: 1
DOI: 10.2174/2212697X01999131127163516









Clinical Significance of Breast Cancer Resistance Protein/ABCG2 in the Management of Malignancy

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Author(s): Yasuo Imai, Hidetsugu Yamagishi, Yuko Ono and Yoshihiko Ueda
Pages 40-53 (14)
Abstract:
Breast cancer resistance protein (BCRP), also termed ABCG2, is a member of an ATP-binding cassette transporter G family, which was originally identified in relation to drug resistance in cancer cells. BCRP intrinsically interacts with a range of substances such as sterols, porphyrins and a variety of dietary compounds, but it mediates extrusion of toxic compounds out of cells and underlies multidrug resistance of cancer cells. Hence, BCRP expression levels in tumor and non-tumor cells may determine response to chemotherapy as well as adverse effects. In the former part of this paper, the latest findings are reviewed regarding clinical significance of BCRP expression in malignancy. In the latter part, reports on single nucleotide polymorphisms (SNPs) of the BCRP gene are reviewed focusing on impacts upon cancer chemotherapy. C421A and C376T, which result in very low and null expression of the protein, respectively, are particularly referred to regarding their phenotypes because of possible importance in cancer chemotherapy. Approximately one tenth of hyperuricemia/gout patients and a considerable part of population with Junior a (-) [jr(a-)] blood type are expected to bear these SNPs on the both alleles. Therefore, genotypic examination of the BCRP gene would be recommended in these populations before the start of chemotherapy including BCRP substrate drugs.
Keywords:
ABCG2, anticancer drug, BCRP, C376T, C421A, cancer, chemotherapy, clinical significance, drug resistance, gout, jr(a-), malignancy, SNPs.
Affiliation:
Department of Pathology, Dokkyo Medical University Koshigaya Hospital, 2-1-50 Minami- Koshigaya, Koshigaya, Saitama 343-8555, Japan.