ABCG2: the key to chemoresistance in cancer stem cells?
Multi-drug chemoresistance remains one of the most common reasons for chemotherapy failure. The membrane transporter protein ABCG2/BCRP1 has been shown in vitro to effectively reduce the intracellular concentrations of several prominent anticancer chemotherapeutic agents such as mitoxantrone and doxorubicin. Intriguingly, cancer stem cells are known to be characterized by multi-drug chemoresistance. Taking into account that the ABCG2(+) subset of tumor cells are often enriched with cells with cancer stem-like phenotypes, it has been proposed that ABCG2 activity underlies the ability of cancer cells to regenerate post-chemotherapy. Furthermore, we also review evidence suggesting that tyrosine kinase inhibitors, including imatinib and gefitinib, are both direct and downstream inactivators of ABCG2 and, therefore, serve as candidates to reverse cancer stem cell chemoresistance and potentially target cancer stem cells.
An
Yi
Y
Stanford University School of Medicine, Stanford, CA 94305, USA.
Ongkeko
Weg M
WM
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins