期刊
CURRENT MEDICINAL CHEMISTRY
卷 18, 期 27, 页码 4237-4249出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/092986711797189682
关键词
ABC transporters; cancer stem cells; drug resistance; drug targets; glycosylation; miRNAs; P-gp; BCRP; MRP; transporter inhibitor
资金
- Associazione Italiana per la Ricerca sul Cancro, Milan
- CARIPLO Foundation
- EU
ATP-binding cassette (ABC) transporters are a large family of proteins implicated in physiological cellular functions. Selected components of the family play a well-recognized role in extruding conventional cytotoxic antitumor agents and molecularly targeted drugs from cells. Some lines of evidence also suggest links between transporters and tumor cell survival, in part unrelated to efflux. However, the study of the precise mechanisms regulating the function of drug transporters (e. g., posttranslational modifications such as glycosylation) is still in its infancy. A better definition of the molecular events clarifying the regulation of transporter levels including regulation by microRNAs may contribute to provide new molecular tools to target such a family of transporters. The present review focuses on the biological aspects that implicate ABC transporters in resistance of tumor cells, including cancer stem cells. Molecular analysis of well-known preclinical systems as well as of cancer stem cell models supports the notion that ABC transporters represent amenable targets for modulation of the efficacy of antitumor agents endowed with different molecular features. Recent achievements regarding tumor cell biology are expected to provide a rationale for developing novel inhibitors that target ABC transporters implicated in drug resistance.
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