Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy

Kohji Noguchi, Kazuhiro Katayama, Junko Mitsuhashi, Yoshikazu Sugimoto

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

The breast cancer resistance protein, BCRP/ABCG2, is a half-molecule ATP-binding cassette transporter that facilitates the efflux of various anticancer agents from the cell, including 7-ethyl-10-hydroxycamptothecin, topotecan and mitoxantrone. The expression of BCRP can thus confer a multidrug resistance phenotype in cancer cells, and its transporter activity is involved in the in vivo efficacy of chemotherapeutic agents. Thus, the elucidation of the substrate preferences and structural relationships of BCRP is essential to understanding its in vivo functions during chemotherapeutic treatments. Single nucleotide polymorphisms (SNPs) have also been found to be key factors in determining the efficacy of chemotherapeutics, and those therapeutics that inhibit BCRP activity, such as the SNP that results in a C421A mutant, may result in unexpected side effects of the BCRP- anticancer drugs interaction even at normal dosages. In order to modulate the BCRP activity during chemotherapy, various compounds have been tested as inhibitors of this protein. Estrogenic compounds including estrone, several tamoxifen derivatives in addition to phytoestrogens and flavonoids have been shown to reverse BCRP-mediated drug resistance. Intriguingly, recently developed molecular targeted cancer drugs, such as the tyrosine kinase inhibitors imatinib mesylate, gefitinib and others, can also interact with BCRP. Since both functional SNPs and inhibitory agents of BCRP modulate the in vivo pharmacokinetics and pharmacodynamics of its substrate drugs, BCRP activity is an important consideration in the development of molecular targeted chemotherapeutics.

Original languageEnglish
Pages (from-to)26-33
Number of pages8
JournalAdvanced Drug Delivery Reviews
Volume61
Issue number1
DOIs
Publication statusPublished - 2009 Jan 31

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Single Nucleotide Polymorphism
irinotecan
Breast Neoplasms
Drug Therapy
Topotecan
Phytoestrogens
Mitoxantrone
ATP-Binding Cassette Transporters
Estrone
Multiple Drug Resistance
Tamoxifen
Drug Interactions
Drug Resistance
Flavonoids
Pharmaceutical Preparations
Antineoplastic Agents
Protein-Tyrosine Kinases
Neoplasms
Estrogens
Pharmacokinetics

Keywords

  • Cancer
  • Drug resistance
  • Kinase inhibitor
  • SNP

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. / Noguchi, Kohji; Katayama, Kazuhiro; Mitsuhashi, Junko; Sugimoto, Yoshikazu.

In: Advanced Drug Delivery Reviews, Vol. 61, No. 1, 31.01.2009, p. 26-33.

Research output: Contribution to journalArticle

Noguchi, Kohji ; Katayama, Kazuhiro ; Mitsuhashi, Junko ; Sugimoto, Yoshikazu. / Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. In: Advanced Drug Delivery Reviews. 2009 ; Vol. 61, No. 1. pp. 26-33.
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